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I. The document summarizes research on matrix metalloproteinases (MMPs), a family of enzymes that degrade extracellular matrix and participate in vascular remodeling. It discusses 12 MMPs and their roles in atherosclerotic plaque development and rupture. II. Studies have shown several MMPs (MMP-1, -2, -3, -9, -12) present in atherosclerotic plaques and implicated in plaque development and rupture. MMP-8 was also found to be associated with collagen degradation in plaque shoulders, a site of rupture. III. The document concludes that MMP-3 and its inhibitor, TIMP-3, are overexpressed in aneurysmal aorta, suggesting inhibition of MMP3
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BMP bone morphogenic protein in spinal surgery
This document discusses the use of bone morphogenetic protein (BMP) in spinal fusions. It provides background on BMP and details several complications that have been reported with its use, including soft tissue swelling, ectopic bone formation, osteolysis, and inadvertent fusions. It also references studies that found higher than reported complication rates associated with BMP and suggests the minimally effective dose has not been determined. Case studies are presented of patients who experienced issues like psoas calcification, seromas, and retrograde ejaculation following procedures using BMP.
Hum. Mol. Genet.-2014-Goldstein-hmg-ddu390
1) Muscle injury in mice lacking the protein γ-sarcoglycan causes an increase in SMAD signaling, which contributes to transforming growth factor β (TGFβ) signaling.
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Bone morphogenetic proteins /certified fixed orthodontic courses by Indian ...
Welcome to Indian Dental Academy
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and offering a wide range of dental certified courses in different formats.
Indian dental academy has a unique training program & curriculum that provides students with exceptional clinical skills and enabling them to return to their office with high level confidence and start treating patients
State of the art comprehensive training-Faculty of world wide repute &Very affordable
Bone Morphogenetic Proteins
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This document provides an overview of bone morphogenetic proteins (BMPs). It discusses the history and discovery of BMPs, their structure and classification. The key characteristics and mechanisms of action of BMPs are described, including their role in signaling pathways and spatial/temporal regulation. The document outlines the functions of BMPs in embryogenesis, tooth morphogenesis, and osseoinduction. It also discusses various delivery systems for BMPs, including local protein therapy using both organic matrices like collagen and inorganic matrices like hydroxyapatite.
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BMP bone morphogenic protein in spinal surgery
This document discusses the use of bone morphogenetic protein (BMP) in spinal fusions. It provides background on BMP and details several complications that have been reported with its use, including soft tissue swelling, ectopic bone formation, osteolysis, and inadvertent fusions. It also references studies that found higher than reported complication rates associated with BMP and suggests the minimally effective dose has not been determined. Case studies are presented of patients who experienced issues like psoas calcification, seromas, and retrograde ejaculation following procedures using BMP.
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MDM2 promotes the ubiquitination and degradation of FOXO transcription factors. The study found that MDM2 binds directly to FOXO1 and FOXO3A, promoting their ubiquitination and proteasome-mediated degradation. This degradation was dependent on FOXO phosphorylation by AKT and the E3 ligase activity of MDM2. Furthermore, activation of p53 led to increased MDM2 levels and degradation of endogenous FOXO3A. Therefore, MDM2 acts as an E3 ubiquitin ligase downstream of p53 to regulate FOXO protein stability.
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1) A study found that using rhBMP-2 on an absorbable collagen sponge resulted in faster fracture healing and fewer secondary interventions compared to standard of care alone.
2) A case report described severe neck swelling in one patient who received rhBMP-2 during cervical spine surgery, likely due to an excessive inflammatory response.
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Bmb 411 presentation open
1. Researchers created "mtDNA-mutator mice" with a defective mitochondrial DNA polymerase that lacked exonuclease activity.
2. These mice accumulated somatic mtDNA mutations over time and exhibited premature aging phenotypes such as weight loss, hair loss, bone loss, and heart abnormalities.
3. The median lifespan of mtDNA-mutator mice was 48 weeks compared to over 2 years in normal mice, providing an experimental link between increased somatic mtDNA mutations, mitochondrial dysfunction, and mammalian aging.
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1) The study found higher levels of MT1-MMP and lower levels of RECK, an MT1-MMP inhibitor, on circulating human CD34+ progenitor cells compared to those in bone marrow. MT1-MMP levels correlated with successful mobilization of CD34+ cells in healthy donors and patients receiving G-CSF treatment.
2) Treatment with G-CSF further increased MT1-MMP and decreased RECK expression on human and mouse hematopoietic cells in a PI3K/Akt-dependent manner. Blocking MT1-MMP impaired chemotaxis and homing of mobilized human CD34+ progenitors.
3) Mobilization of human progen
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1) Two studies found that coronary segments with 50-80% stenosis at baseline had higher risks of total occlusion at follow-up than segments with less severe stenosis.
2) Another study found that prior to myocardial infarction, 29% of culprit lesions showed 0-50% stenosis, while 4.1-7.9% showed 50-90% stenosis.
3) A review concluded that the majority of infarcts evolve from angiographically mild to moderate stenoses, not severe stenoses.
4) A study on plaque rupture found that two-thirds of acute coronary disease
261 molecular genetics and micro arrays
This document summarizes several studies that used microarray technology to analyze gene expression in cardiovascular tissues and cells:
1) Studies analyzed atherosclerotic lesions and correlated gene expression with the vulnerability and pathogenesis of lesions.
2) Other studies analyzed gene expression changes in cardiac growth, development, and response to injury as well as during viral infection.
3) Gene expression in vascular cells and tissues was also analyzed in response to mechanical stress, inflammation, and other cardiovascular conditions like atherosclerosis and hypertension.
053 histologic evidence of spio accumulation in vulnerable plaques
This study examined the accumulation of superparamagnetic iron oxide (SPIO) nanoparticles in vulnerable atherosclerotic plaques. In vitro experiments demonstrated that human macrophages actively take up fluorescent-labeled SPIO particles over 24 hours in a time- and concentration-dependent manner. In vivo studies in mice and rabbit models of atherosclerosis found SPIO particles in macrophage-rich areas of plaques, with a strong correlation between iron staining and foam cell density. Cytokine treatment increased SPIO uptake in plaques. The results suggest MRI using SPIO has potential for noninvasively assessing monocyte recruitment in vulnerable plaques.
048 adventitial fat presentation
1) The study investigated the uptake of SPIO (superparamagnetic iron oxide), an MRI contrast agent, by periadventitial fat in an atherosclerosis mouse model.
2) Results showed significantly greater uptake of iron in the periadventitial fat of apoE k/o mice compared to control mice, as measured by iron particles and area.
3) Preliminary evidence also suggests uptake of iron in the periadventitial fat of atherosclerotic rabbits and humans, suggesting macrophage-like activity in this tissue that warrants further investigation into its role in atherosclerosis and potential applications for plaque imaging.
243 b cell
I. The document summarizes several studies that investigated the role of the immune system, particularly B cells, in atherosclerosis using mouse models.
II. One study found that RAG-1 deficient mice, which lack functional B and T cells, exhibited increased neointimal formation following arterial injury compared to wild type mice. Transferring B cells from wild type mice to RAG-1 deficient mice reduced neointimal formation.
III. Overall, the studies suggest that B cells may play a protective role against atherosclerosis by reducing plaque formation and progression. The mechanism may involve antibodies that target oxidation-specific epitopes, but this requires further investigation.
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13987.full
MDM2 promotes the ubiquitination and degradation of FOXO transcription factors. The study found that MDM2 binds directly to FOXO1 and FOXO3A, promoting their ubiquitination and proteasome-mediated degradation. This degradation was dependent on FOXO phosphorylation by AKT and the E3 ligase activity of MDM2. Furthermore, activation of p53 led to increased MDM2 levels and degradation of endogenous FOXO3A. Therefore, MDM2 acts as an E3 ubiquitin ligase downstream of p53 to regulate FOXO protein stability.
J. Biol. Chem.-2008-Lin-15003-14
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EZH2 Abstract Final
Ezh1 and Ezh2 are histone methyltransferases that are required for normal skeletal growth. Mice with a complete knockout of Ezh1 and cartilage-specific knockout of Ezh2 exhibited postnatal growth retardation and impaired longitudinal bone growth. The knockout mice showed decreased proliferation and size of growth plate chondrocytes as well as premature differentiation into hypertrophic chondrocytes. This indicates that loss of Ezh1 and Ezh2 inhibits chondrocyte proliferation and causes premature differentiation, impairing skeletal growth.
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Five unrelated families with recessive ATG7 variants presented with developmental defects including ataxia, developmental delay, musculoskeletal abnormalities, and facial dysmorphism. Analysis of patient samples found undetectable ATG7 protein levels and increased P62 levels, indicating defective autophagy. Introduction of wild-type ATG7 into patient cells restored autophagy, demonstrating the critical role of ATG7 in neural and musculoskeletal development. The findings expand understanding of autophagy deficiencies in human disease.
Seminario sara y Juan D
This study summarizes the developmental consequences of defective ATG7-mediated autophagy in humans. The study analyzed 5 unrelated families with recessive ATG7 variants who presented with cerebellar hypoplasia, thin corpus callosum, ataxia, musculoskeletal abnormalities, and developmental delays. Biopsies found ATG7 to be undetectable and decreased in patient myoblasts, with increased P62 levels. The results strengthen the understanding of autophagy in human disease and expand the clinical phenotypes associated with congenital autophagy deficiencies. Molecular techniques were crucial for analyzing this genetic disease and provide options for future treatment.
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Abstract
Mitogen-Activated Protein Kinase (MAPK) pathway is a signal transduction pathway that functions in a wide range of physiological and pathophysiological cellular events including cell proliferation, differentiation, apoptosis, migration, inflammation, metabolic disorders and diseases. In skeletal muscle, it plays an essential role in muscle fiber specialization, muscle mass maintenance, damage induced muscle regeneration and muscle diseases. This review provides an overview of MAPK pathway and its pathophysiological role in skeletal muscle diseases with a primary focus on muscular dystrophy and atrophy.
Matrix metalloproteinases
Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that degrade extracellular matrix components. MMPs play important roles in tissue remodeling during processes like wound healing and organ development by breaking down collagen, elastin, fibronectin and other matrix proteins. Their activity is regulated by tissue inhibitors of metalloproteinases (TIMPs). Abnormal MMP activity is associated with diseases like cancer, atherosclerosis, and rheumatoid arthritis by facilitating tissue invasion or destruction.
Bone morphogentic protein
1) BMPs play an important role in tooth development and regeneration by signaling between dental epithelium and mesenchyme. They are expressed in a spatial and temporal sequence that governs tooth patterning and morphogenesis.
2) Progenitor/stem cells found in dental pulp and periodontal ligament have the potential to differentiate into odontoblasts and other dental tissues when exposed to BMPs.
3) The application of BMPs, stem cells, and appropriate extracellular matrix scaffolds could facilitate the regeneration of dental and craniofacial tissues through recapitulating embryonic development pathways.
930710.v2
This document summarizes the bifunctional role of glycogen synthase kinase-3 beta (GSK-3β) in regulating cell death pathways. GSK-3β can both promote and inhibit apoptosis depending on cell type and signaling environment. It promotes apoptosis by inhibiting pro-survival factors and facilitating pro-apoptotic factors like p53. However, it also inhibits apoptosis under basal conditions by promoting degradation of p53 through MDM2 and stabilizing NF-κB, which protects against tumor necrosis factor-induced cell death. Due to its complex roles in cell survival, GSK-3β is an important target for drug development in diseases like cancer.
BMES poster 2013
Mesenchymal stem cells (MSCs) show promise for treating immune disorders and degenerative diseases. However, targeting MSCs to damaged tissue sites is challenging. The researchers hypothesized that engineering MSCs to express leukocyte adhesion molecules could enhance their homing ability. They coupled a recombinant form of P-selectin glycoprotein ligand-1 (PSGL-1), which mediates leukocyte rolling, to MSCs. This non-covalently coupled the PSGL-1 to the MSC surface. MSCs modified with PSGL-1 were then able to tether and roll on endothelial cells under flow, mimicking leukocyte behavior, suggesting this approach may help target MSCs to sites of injury and inflammation.
URO117_Poster (1)
This study analyzed 95 non-synonymous single nucleotide polymorphisms (nsSNPs) in the human FXN gene, which codes for the frataxin protein involved in Friedreich's ataxia. Eight computational tools were used to evaluate the potential effects of the nsSNPs on frataxin protein stability and activity. Molecular dynamics simulations were performed on the native and mutant frataxin protein structures over time to analyze structural and functional changes from the nsSNPs. The results of this computational analysis of the nsSNPs could provide insight into how functional nsSNPs may contribute to causing Friedreich's ataxia.
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1) A study found that using rhBMP-2 on an absorbable collagen sponge resulted in faster fracture healing and fewer secondary interventions compared to standard of care alone.
2) A case report described severe neck swelling in one patient who received rhBMP-2 during cervical spine surgery, likely due to an excessive inflammatory response.
3) A study found that BMP-7 blocks the transition of mesothelial cells to mesenchymal cells and prevents peritoneal membrane damage in dialysis patients by antagonizing TGF-beta 1 and inhibiting epithelial-to-mesenchymal transition.
Epigenetic regulation of cardiogenesis
Présentation de Michel Pucéat réalisée durant le cours du réseau international des instituts Pasteur de "Médecine Génomique: du diagnostic à la thérapie " (17-21 octobre 2016)
Bmb 411 presentation open
1. Researchers created "mtDNA-mutator mice" with a defective mitochondrial DNA polymerase that lacked exonuclease activity.
2. These mice accumulated somatic mtDNA mutations over time and exhibited premature aging phenotypes such as weight loss, hair loss, bone loss, and heart abnormalities.
3. The median lifespan of mtDNA-mutator mice was 48 weeks compared to over 2 years in normal mice, providing an experimental link between increased somatic mtDNA mutations, mitochondrial dysfunction, and mammalian aging.
JCI0936541
1) The study found higher levels of MT1-MMP and lower levels of RECK, an MT1-MMP inhibitor, on circulating human CD34+ progenitor cells compared to those in bone marrow. MT1-MMP levels correlated with successful mobilization of CD34+ cells in healthy donors and patients receiving G-CSF treatment.
2) Treatment with G-CSF further increased MT1-MMP and decreased RECK expression on human and mouse hematopoietic cells in a PI3K/Akt-dependent manner. Blocking MT1-MMP impaired chemotaxis and homing of mobilized human CD34+ progenitors.
3) Mobilization of human progen
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507 stenosis severity and risk benefit
This document discusses several studies on the relationship between stenosis severity and risks of coronary occlusion and acute coronary syndrome:
1) Two studies found that coronary segments with 50-80% stenosis at baseline had higher risks of total occlusion at follow-up than segments with less severe stenosis.
2) Another study found that prior to myocardial infarction, 29% of culprit lesions showed 0-50% stenosis, while 4.1-7.9% showed 50-90% stenosis.
3) A review concluded that the majority of infarcts evolve from angiographically mild to moderate stenoses, not severe stenoses.
4) A study on plaque rupture found that two-thirds of acute coronary disease
261 molecular genetics and micro arrays
This document summarizes several studies that used microarray technology to analyze gene expression in cardiovascular tissues and cells:
1) Studies analyzed atherosclerotic lesions and correlated gene expression with the vulnerability and pathogenesis of lesions.
2) Other studies analyzed gene expression changes in cardiac growth, development, and response to injury as well as during viral infection.
3) Gene expression in vascular cells and tissues was also analyzed in response to mechanical stress, inflammation, and other cardiovascular conditions like atherosclerosis and hypertension.
053 histologic evidence of spio accumulation in vulnerable plaques
This study examined the accumulation of superparamagnetic iron oxide (SPIO) nanoparticles in vulnerable atherosclerotic plaques. In vitro experiments demonstrated that human macrophages actively take up fluorescent-labeled SPIO particles over 24 hours in a time- and concentration-dependent manner. In vivo studies in mice and rabbit models of atherosclerosis found SPIO particles in macrophage-rich areas of plaques, with a strong correlation between iron staining and foam cell density. Cytokine treatment increased SPIO uptake in plaques. The results suggest MRI using SPIO has potential for noninvasively assessing monocyte recruitment in vulnerable plaques.
048 adventitial fat presentation
1) The study investigated the uptake of SPIO (superparamagnetic iron oxide), an MRI contrast agent, by periadventitial fat in an atherosclerosis mouse model.
2) Results showed significantly greater uptake of iron in the periadventitial fat of apoE k/o mice compared to control mice, as measured by iron particles and area.
3) Preliminary evidence also suggests uptake of iron in the periadventitial fat of atherosclerotic rabbits and humans, suggesting macrophage-like activity in this tissue that warrants further investigation into its role in atherosclerosis and potential applications for plaque imaging.
243 b cell
I. The document summarizes several studies that investigated the role of the immune system, particularly B cells, in atherosclerosis using mouse models.
II. One study found that RAG-1 deficient mice, which lack functional B and T cells, exhibited increased neointimal formation following arterial injury compared to wild type mice. Transferring B cells from wild type mice to RAG-1 deficient mice reduced neointimal formation.
III. Overall, the studies suggest that B cells may play a protective role against atherosclerosis by reducing plaque formation and progression. The mechanism may involve antibodies that target oxidation-specific epitopes, but this requires further investigation.
242 lipid lowering
Lipid lowering through dietary changes can reduce oxidative stress and endothelial inflammation in a rabbit model of atherosclerosis. Specifically:
- Rabbits fed an atherogenic diet for 20 months showed accumulation of oxidized LDL and expression of vascular cell adhesion molecule-1 (VCAM-1) by endothelial cells, compared to baseline levels.
- Rabbits then placed on a low-cholesterol diet for 16 months showed reduced oxidative stress, decreased oxidized LDL and VCAM-1, and improved endothelial cell function and structure.
- This suggests lipid lowering can decrease vascular inflammation and stabilize plaques by reducing oxidative stress, independent of direct effects on LDL cholesterol levels.
140 mr imaging of fibrin
The document discusses research into using MRI with fibrin-targeted gadolinium contrast agents to detect vulnerable plaques associated with heart attacks, presenting findings that this approach can successfully identify fibrin deposits in thrombi in animal studies and has potential for sensitive detection of injured plaques in humans; it also notes the need for more studies to develop highly sensitive targeted contrast agents for multiple imaging modalities to identify vulnerable plaque features beyond structure.
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This document provides background on Jacques Barth, an expert in cardiovascular imaging and risk assessment. It discusses the evolution of ultrasound technology for measuring intima-media thickness (IMT) from 1986 to 2005. IMT is an early marker of atherosclerosis and cardiovascular risk. The document also addresses issues around vulnerable plaques, reporting IMT measurements, and assessing cardiovascular risk in children and adolescents.
Acc v porg
This document discusses the use of coronary CT angiography (CTA) to detect and characterize coronary atherosclerosis beyond just detecting coronary stenoses. CTA can identify calcified plaques, non-calcified plaques, and mixed plaques. It can detect atheromas and characterize plaque density. CTA can also identify intracoronary thrombi and myocardial infarction scars. The document outlines the CTA scanning parameters and techniques used to minimize motion artifacts and optimize image quality for plaque detection and characterization.
258 dr renu virmani
Dr. Renu Virmani is the Chairperson of the Department of Cardiovascular Pathology at the Armed Forces Institute of Pathology in Washington, DC. She received her medical degrees in India and has held positions at multiple universities in the United States. Dr. Virmani has established an independent research program focused on cardiovascular pathology, publishing over 300 papers. She leads a department of 23 researchers studying devices, sudden death, and cardiovascular diseases.
226 statins are overrated
Statins are not effective enough and their benefits are delayed. Vulnerable plaques are usually found in multiple locations. While statins may lower lipids and have anti-inflammatory effects within 6 weeks, they do not significantly reduce mortality within the first year of treatment. Over 40% of deaths in statin trials still occurred in the statin groups. Local therapies in addition to statins may be needed to stabilize vulnerable plaques and buy more time for other treatments to have an effect.
1
Plaque thermography uses a catheter with a single thermistor to measure heat levels in arteries and identify areas of plaque buildup. The technique works best in vessels with stenoses over 50% and has limitations in large vessels where the thermistor can flutter or "flail". The catheter comes in sizes from 3 to 4.5 French.
233 cd40
CD40 and its ligand CD40L play an important role in atherosclerosis by promoting inflammation. Statins can limit the expression of CD40 and CD40L, thereby reducing inflammation. Oxidized LDL increases the expression of CD40 and CD40L on endothelial cells, smooth muscle cells, and macrophages, further promoting atherosclerosis. CD40L also contributes to thrombosis and restenosis. While CD40 does not seem to affect early plaque formation, its deficiency is associated with more stable plaques at advanced stages of atherosclerosis.
172 nir spectroscopy
This document discusses the use of near-infrared (NIR) spectroscopy to analyze atherosclerotic plaques. It provides definitions of NIR spectroscopy and describes how it allows chemical analysis of plaques. Studies are cited that have used NIR spectroscopy to detect plaque components like lipid pools, thin fibrous caps, and inflammatory cells. The document discusses both advantages and disadvantages of using NIR spectroscopy for in vivo chemical analysis of plaques. It concludes that NIR spectroscopy shows potential for identifying vulnerable plaques but questions remain about its ability to distinguish plaque types in living patients.
076 cardiac magnetic resonance imaging
MRI can effectively evaluate patients presenting to the emergency department with possible acute coronary syndrome. In a study of 161 such patients, MRI had higher sensitivity and specificity than electrocardiography, troponin levels, or clinical risk scores for detecting acute coronary syndrome, non-ST elevation myocardial infarction, and ischemic heart disease. Regional wall motion abnormalities detected by MRI had 89% sensitivity and 99% specificity for detecting ischemic heart disease compared to 67% sensitivity and 99% specificity for detecting ischemic heart disease using delayed hyperenhancement. MRI provides accurate information to guide patient management in the emergency department.
031
1) This study investigated the use of super paramagnetic iron oxide (SPIO) nanoparticles and MRI to detect active inflammation in atherosclerotic plaques.
2) In mouse and rabbit models of atherosclerosis, SPIO accumulated in atherosclerotic lesions and correlated with histological markers of inflammation.
3) MRI of plaques in these animals showed changes after SPIO injection, indicating SPIO can help identify actively inflamed plaques.
4) A current human clinical trial is evaluating if SPIO-enhanced MRI can detect vulnerable carotid plaques by comparing MRI to histology of plaques removed in surgery.
247 ebct vs conventional risk factors
The calcium score provides a more accurate measure of cardiac risk than conventional risk factors alone. It can identify those at higher or lower risk who may be misclassified by conventional methods. Using the calcium score to adjust a patient's "heart age" can reclassify over a third of intermediate-to-high risk patients as either lower or higher risk compared to their conventional risk assessment. This better risk stratification is important for determining appropriate prevention and treatment strategies.
152 spio photographs
SPIO particles coated with different materials were tested for their effects on nitric oxide production in macrophages. Dextran coated SPIO particles (SPIO-2) produced the lowest level of nitric oxide, while lipid coated particles (SPIO-3) produced higher levels and uncoated particles (SPIO-4) produced the highest levels. Fluorescently labeled SPIO particles were found inside macrophages harvested from mice injected with the particles, and iron particles were also seen inside circulating monocytes of injected mice. Aortic walls from Apo E deficient mice appeared darker after injection of SPIO particles and contained many iron particles, but aortic walls from control mice did not show this change and had few iron particles.
042 introducing a novel model
This document summarizes studies examining methods to track macrophage recruitment into atherosclerotic plaques. Initial EM studies in pigs found bi-directional movement of foam cells through the endothelium. Subsequent studies labeled monocytes with fluorescent dyes or microspheres and tracked their recruitment to plaques in pigs and mice. A newer method used PCR to detect transfusion of male monocytes into female mice. The presented study examined the effects of cytokines on SPIO uptake in plaques of ApoE-deficient mice, finding greater iron particle deposition in cytokine-treated mice, indicating increased monocyte recruitment. This suggests SPIO could non-invasively monitor monocyte recruitment during MRI.
162 calcium imaging
Scores >400 are associated with a 10-fold increased risk of future events. Calcium imaging should be used routinely to assess risk. Matthew Budoff is an assistant professor of cardiology who discloses a relationship with Imatron, Inc as a speaker.
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053 histologic evidence of spio accumulation in vulnerable plaques
053 histologic evidence of spio accumulation in vulnerable plaques
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Mmp in cvd
What are matrix metalloproteinases?
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Diagnostic and Prognostic utility
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Mast cell - Oral Pathology
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MULTIPLE MYELOMA CELLS
THIS IS A RESEARCH PAPER PPT THAT REPRESENT THE TOPIC- ANALYSIS OF THE RELATIONSHIP BETWEEN MULTIPLE MYELOMA CELLS AND THEIR MICROENVIROMENT .....
Bmc Cancer Mmp3 2010
This study investigated the association between the MMP-3 promoter polymorphism (-1171 5A->6A) and risk of oral submucous fibrosis (OSMF) and head and neck squamous cell carcinoma (HNSCC) in an Indian population. The authors genotyped 362 subjects, including 101 OSMF cases, 135 HNSCC cases, and 126 healthy controls. They found the 5A allele frequency was higher in OSMF (0.15) and HNSCC (0.13) compared to controls (0.07). Statistical analysis revealed a significant difference in 5A genotype frequency between OSMF and controls (p=0.01, OR=2.26) and between HNSCC
Ojchd.000534
This document summarizes research on CRP3/MLP (cysteine-rich protein 3/muscle LIM protein) and its role in vein graft failure and arterialization. It discusses how CRP3/MLP expression is normally present in arteries but absent in veins, but becomes upregulated in veins during adaptation to arterial hemodynamics. Studies in a CRP3/MLP knockout rat model showed it acts as a key modifier of vein remodeling by sensitizing stretched smooth muscle cells to apoptosis. The research suggests CRP3/MLP may be a new target to prevent neointimal growth and vein graft failure, and could help predict outcomes of vascular therapies.
METALOPROTEINASAS.pdf
1. Metaloproteinases (MMPs) are enzymes that maintain and degrade the extracellular matrix during tissue repair and remodeling. MMPs participate in wound healing, angiogenesis, and cancer metastasis.
2. MMPs are classified into subgroups based on their protein targets, such as collagens, gelatinases, and matrilysins. They have domains for signaling, catalytic activity, and substrate binding.
3. MMP activity is regulated by tissue inhibitors of metalloproteinases (TIMPs) and imbalanced MMP/TIMP expression contributes to cancer progression and metastasis by continuously remodeling the extracellular matrix.
Matrixmetalloproteinase
Matrix metalloproteinases (MMPs) are enzymes that degrade components of the extracellular matrix. They are implicated in various neurological conditions and play important roles in processes like synaptic remodeling. More recently, MMPs have been shown to regulate neural stem cell biology and remyelination, suggesting their importance in nervous system regeneration. While MMPs serve beneficial functions, their upregulation in conditions like neuroinflammation and neurodegeneration can also contribute to tissue damage.
Esv3n3
The document discusses the roles of Liver X receptors (LXRs) and peroxisome proliferator-activated receptors (PPARs) in regulating matrix metalloproteinase-9 (MMP-9) expression in macrophages and their implications in atherosclerosis. It reports that LXR and PPAR activation inhibits MMP-9 expression, reducing foam cell accumulation and atherosclerosis progression in mice studies. While PPARγ ligands suppress MMP-9 even in PPARγ deficient cells, the mechanisms of this effect and whether LXR ligands similarly regulate MMP-9 in LXR deficient cells requires further investigation. The LXR agonist GW3965 may have potential for stabilizing vulnerable atherosclerotic plaques by downregulating
510 does lxr links lipid metabolism to inflammation, or ppar
The document discusses the roles of Liver X receptors (LXRs) and peroxisome proliferator-activated receptors (PPARs) in regulating matrix metalloproteinase-9 (MMP-9) expression in macrophages and their implications in atherosclerosis. It reports that LXR and PPAR activation inhibits MMP-9 expression, reducing foam cell accumulation and atherosclerosis progression in mice studies. While PPARγ ligands suppress MMP-9 even in PPARγ deficient cells, the mechanisms of this effect and whether LXR ligands similarly regulate MMP-9 in LXR deficient cells requires further investigation. The LXR agonist GW3965 may have potential for stabilizing vulnerable atherosclerotic plaques by downregulating
510 does lxr links lipid metabolism to inflammation, or ppar
510 does lxr links lipid metabolism to inflammation, or pparSociety for Heart Attack Prevention and Eradication
The document discusses the roles of Liver X receptors (LXRs) and peroxisome proliferator-activated receptors (PPARs) in regulating matrix metalloproteinase-9 (MMP-9) expression in macrophages and their implications in atherosclerosis. It reports that LXR and PPAR activation inhibits MMP-9 expression, reducing foam cell accumulation and atherosclerosis progression in mouse models. While PPARγ ligands suppress MMP-9 even in PPARγ-deficient cells, the mechanisms by which they and LXR ligands regulate MMP-9 independently require further investigation. The LXR agonist GW3965 may help stabilize vulnerable atherosclerotic plaques by downregulating MMP-9 and inflammatory pathways.Polymophism in the promoter
The document discusses several studies related to atherosclerosis and cardiovascular disease:
1) A study finds that a polymorphism in the Fas gene promoter region is a genetic risk factor for myocardial infarction by modulating Fas expression.
2) Immunoglobulin treatment suppresses atherosclerosis in mice via its Fc portion by reducing macrophage accumulation in lesions.
3) Inhibition of NF-kB reduces inflammatory molecule expression and attenuates atherosclerosis in mice.
4) MMP-8 may represent a new collagenolytic pathway in acute plaque disruption based on its levels in carotid plaques from patients.
KLF4-dependent phenotypic modulation of smooth muscle cells has a key role in...
This study aimed to better understand the contributions of smooth muscle cells (SMCs) to atherosclerotic plaque pathogenesis using a mouse model that allows SMC lineage tracing. The researchers found that traditional methods using SMC markers like ACTA2 failed to identify more than 80% of SMC-derived cells within advanced plaques. These unidentified SMC-derived cells exhibited phenotypes of other cell types such as macrophages and mesenchymal stem cells. Conditional knockout of the transcription factor KLF4 in SMCs reduced the numbers of these SMC-derived macrophage- and stem cell-like cells, significantly decreasing plaque size and increasing stability markers. This suggests KLF4 plays a key role in regulating phenotypic transitions of S
SSR 2014-poster-Matrix Metallopeptidase 12 and the Endovascular Invasive Trop...
This poster presentation summarizes research on the role of matrix metallopeptidase 12 (MMP12) in the invasive trophoblast lineage during placentation. The researchers found that MMP12 is dramatically upregulated in invasive trophoblast cells lining the uterine spiral arteries during hypoxic conditions. They also observed MMP12 upregulation during trophoblast differentiation induced by hypoxia in vitro. To further study MMP12's role, they used TALEN genome editing to generate a mutant rat model lacking MMP12. This Mmp12 mutant rat model will enable them to evaluate the involvement of MMP12 in uterine spiral artery remodeling during placentation.
Matrix metalloproteinase 2 (MMP-2) attenuates brain tumour growth (Feb.01,2013)
1) The study examined the role of MMP-2 in astrocytoma growth and found that MMP-2 surprisingly attenuates brain tumour growth, in contrast to previous beliefs.
2) MMP-2 was found to promote macrophage recruitment and vascular repair in brain tumours, limiting their growth. Lack of MMP-2 reduced macrophage recruitment and promoted tumour growth.
3) MMP-2 is not involved in vascular destabilization commonly associated with malignant brain tumours, but rather is part of a tissue repair response that constrains tumour growth. Therefore, MMP-2 is not a suitable target for brain cancer treatment.
229 propagermanium
The document discusses a study that found propagermanium, an organic germanium compound, reduces atherosclerosis in mice by inhibiting macrophage infiltration. Propagermanium inhibits the MCP-1/CCR2 pathway, which plays an important role in macrophage recruitment during plaque formation. The study showed propagermanium treated mice had significantly smaller atherosclerotic lesions and fewer macrophages in plaques than untreated mice. By suppressing macrophage infiltration through the MCP-1/CCR2 pathway, propagermanium may help prevent atherosclerosis and be a potential drug for treating vulnerable plaque.
229 propagermanium
The document discusses a study that found propagermanium, an organic germanium compound, reduces atherosclerosis in mice by inhibiting macrophage infiltration. Propagermanium inhibits the MCP-1/CCR2 pathway, which plays an important role in macrophage recruitment during plaque formation. The study showed propagermanium treated mice had significantly smaller atherosclerotic lesions and fewer macrophages in plaques than untreated mice. By suppressing macrophage infiltration through the MCP-1 receptor, propagermanium may prevent atherosclerosis and be a potential drug for treating vulnerable plaque.
Esv2n24
The document discusses a study that found propagermanium, an organic germanium compound, reduces atherosclerosis in mice by inhibiting macrophage infiltration. Propagermanium inhibits the MCP-1/CCR2 pathway, which plays an important role in macrophage recruitment during plaque formation. The study showed propagermanium treated mice had significantly smaller atherosclerotic lesions and fewer macrophages in plaques than untreated mice. By suppressing macrophage infiltration through the MCP-1 receptor, propagermanium may prevent atherosclerosis and be a potential drug for treating vulnerable plaque.
Mmp Rev J Biomed Sc 2010
This document summarizes a research article that discusses genetic polymorphisms of matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs), in potentially malignant and malignant head and neck lesions. It describes how MMPs degrade the extracellular matrix, a key event in tumor progression and metastasis. It reviews the classification of MMPs and their substrates. It also discusses how MMPs and TIMPs are regulated and expresses polymorphisms that may be associated with cancer susceptibility and prognosis.
cancer 3.pdf
Artemisinin relieves osteoarthritis by activating mitochondrial autophagy through reducing TNFSF11 expression and inhibiting PI3K/AKT/mTOR signaling in cartilage. The study found that artemisinin treatment downregulated cartilage degradation proteins and inflammatory factors in IL-1β-stimulated chondrocytes. Gene sequencing revealed that artemisinin treatment significantly downregulated TNFSF11 expression, which encodes RANKL, a factor involved in osteoclast formation. The study also showed that artemisinin activated autophagy and relieved cartilage damage by inhibiting the PI3K/AKT/mTOR signaling pathway in IL-1β-induced chondrocytes.
Rejuvenation of Aging HSC
This document summarizes a study that found that inhibiting mTOR signaling through the use of rapamycin can extend lifespan in mice by reducing aging in hematopoietic stem cells (HSC). The study showed that mTOR activation leads to premature aging in HSC, decreasing their function over time. Treatment with rapamycin rescued HSC function in aged mice by reducing markers of aging. Additionally, rapamycin treatment was found to increase lifespan in mice, demonstrating that inhibiting mTOR can extend longevity.
Similar to 171 mm ps the dirty dozen (20)
510 does lxr links lipid metabolism to inflammation, or ppar
510 does lxr links lipid metabolism to inflammation, or ppar
510 does lxr links lipid metabolism to inflammation, or ppar
510 does lxr links lipid metabolism to inflammation, or ppar
KLF4-dependent phenotypic modulation of smooth muscle cells has a key role in...
KLF4-dependent phenotypic modulation of smooth muscle cells has a key role in...
SSR 2014-poster-Matrix Metallopeptidase 12 and the Endovascular Invasive Trop...
SSR 2014-poster-Matrix Metallopeptidase 12 and the Endovascular Invasive Trop...
Matrix metalloproteinase 2 (MMP-2) attenuates brain tumour growth (Feb.01,2013)
Matrix metalloproteinase 2 (MMP-2) attenuates brain tumour growth (Feb.01,2013)
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This document outlines an approach to identifying and managing coronary risk. It recommends that prevention must be the primary goal through intensive global risk factor reduction for all patients with clinically apparent heart disease. It also recommends identifying asymptomatic high-risk individuals through testing like the Framingham Risk Score so they can receive prevention. It proposes a risk stratification approach from low to very high risk based on annual risk levels and corresponding testing and treatments, with very high risk patients receiving the most intensive treatments like invasive detection of unstable plaques and procedures like CABG or multiple drug-eluting stents.
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101205 shape aha 2005 f
Zahi A. Fayad is an Associate Professor who studies molecular imaging of atherosclerosis using MRI. His research focuses on developing targeted contrast agents to noninvasively detect unstable plaque. Some agents under investigation include annexin A5 labeled with a radioisotope to detect apoptosis, FDG-PET to assess plaque activity, and fibrin-targeted and MMP-targeting Gd-based contrasts. Additional work involves lipid-based particulate agents using reconstituted HDL or iron oxide nanoparticles. The goal is to improve MRI detection sensitivity and specificity for high-risk plaque characterization.
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This document proposes a non-invasive method using SPIO (super paramagnetic iron oxide) nanoparticles to image macrophage infiltration and inflammation in vulnerable atherosclerotic plaques. Rabbits and mice were injected with SPIO, which accumulated in inflamed plaque areas correlated with macrophage density. SPIO-enhanced MRI then successfully identified these inflamed plaques non-invasively in vivo. This technique could provide a way to detect rupture-prone plaques and better understand plaque vulnerability.
Acc presentation (1)
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Acc presentation lipid coated(2)
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Acc2002 thermography
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#1 killer of human beings in the 21st century
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259 crp as a risk factor
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Among the factors that lead to the occurrence of gastrointestinal infections are the hygienic and sanitary deficiencies that characterize our markets and other places where raw or cooked food is sold, poor environmental sanitation in communities, deficiencies in water treatment (or in the process of its plumbing), risky hygienic-sanitary habits (not washing hands after major and/or minor needs), among others.
These are generally consequences (signs and symptoms) resulting from gastrointestinal infections: diarrhea, vomiting, fever and malaise, among others.
The treatment consists of replacing lost liquids and electrolytes (drinking drinking water and other recommended liquids, including consumption of juicy fruits such as papayas, apples, pears, among others that contain water in their composition).
To prevent this, it is necessary to promote health education, improve the hygienic-sanitary conditions of markets and communities in general as a way of promoting, preserving and prolonging PUBLIC HEALTH.
Gastritis and Gastric Health
Gastric Health is one of the most relevant concerns in human health, with gastrointestinal infections being among the main illnesses that affect humans.
Among gastric problems, we have GASTRITIS AND GASTRIC ULCERS as the main public health problems. Gastritis and gastric ulcers normally result from inflammation and corrosion of the walls of the stomach (gastric mucosa) and are generally associated (caused) by the bacterium Helicobacter pylor, which, according to the literature, this bacterium settles on these walls (of the stomach) and starts to release urease that ends up altering the normal pH of the stomach (acid), which leads to inflammation and corrosion of the mucous membranes and consequent gastritis or ulcers, respectively.
In addition to bacterial infections, gastritis and gastric ulcers are associated with several factors, with emphasis on prolonged fasting, chemical substances including drugs, alcohol, foods with strong seasonings including chilli, which ends up causing inflammation of the stomach walls and/or corrosion. of the same, resulting in the appearance of wounds and consequent gastritis or ulcers, respectively.
Among patients with gastritis and/or ulcers, one of the dilemmas is associated with the foods to consume in order to minimize the sensation of pain and discomfort. Recently uploaded (20)
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171 mm ps the dirty dozen
- 1. Editorial Slides VP Watch, January 30, 2002, Volume 2, Issue 4 MMPs: The Dirty Dozen!
- 2. MMP 1 Collagenase MMP 11 Stromelysin-3 MMP 2 Gelatinase A MMP 12 Macrophage Metalloelastase MMP 3 Stromelysin-1 MMP 13 Collagenase-3 MMP 7 Matrilysin MMP 14 MT-MMP-1 MMP 8 Neutrophil Collagenase MMP 15 MT-MMP-2 MMP 9 Gelatinase B MMP 16 MT-MMP-3 MMP 10 Stromelysin-2 MMP 17 MT-MMP-4 MMP 20 Enamelysin Adapted from R&D SYSTEMS www.rndsystems.com
- 3. The MMPs constitute a family of endopeptidases that need zinc and calcium for their function.1 MMPs are enzymes that participate in the physiological and pathological remodeling of extra- cellular matrix. 2 The ability of certain MMPs, such as MMP-2, MMP-3, MMP-9, and MMP-12, to hydrolyze elastin is of particular importance in terms of their effects on the vasculature. 1
- 4. Several studies have shown the presence of matrix metalloproteinases 1, 2, 3, 9 and 12 in atherosclerotic plaque development and rupture.3,6 Recently MMP-8 was shown co-localized with cleaved but not intact type I collagen within the shoulder region of the plaque, a frequent site of rupture. 5
- 5. MMPs have the ability to react with specific tissue inhibitors of metalloproteinases (TIMPs) to form enzymatically inactive complexes. 1 Herman, Libby, and colleagues found that the serine proteinase tissue factor pathway inhibitor- 2 (TFPI-2) can function as an MMP inhibitor. 4 Sukhova, Libby, and colleagues found that the presence of cathepsins K and S at sites of vascular matrix remodeling and the ability of SMC and macrophages to use these enzymes to degrade elastin supports a role for non-MMP proteinases in vessel wall remodeling and plaque rupture. 7
- 6. Pyo and colleagues showed that targeted gene disruption of matrix etalloproteinase-9 (gelatinase B) suppresses development of experimental abdominal aortic aneurysms.12 Libby and others found that statins can reduce MMP expression in atheroma and that cell- permeant statins can increase SMC number and collagen gene expression in vivo. 9
- 7. As highlighted in this week VP Watch, Carrell and colleagues found that both abdominal aortic aneurysm (AAA) and aortic occlusive disease (AOD) walls express similar levels of a wide range of MMPs, including cell membrane–bound MT- MMPs. 11 They determined that stromelysin-1 (MMP-3) and tissue inhibitors of metalloproteinases-3 were over-expressed in the AAA samples and may be involved in aneurysm pathogenesis. 11
- 8. Conclusion: I. MMP3 and its inhibitor (TIMP-3) are over expressed in atherosclerotic aneurysmal aorta. II. Inhibition of MMP3 might be a potential therapeutic approach for treatment of atherosclerotic aneurysmal disorders. Similarly it may offer therapeutic opportunities for plaque stabilization and prevention of rupture.
- 9. Questions: I. Having dozens of MMPs involved in atherosclerotic plaque development and/or complication, the question is how effectively inhibition of one MMP may prevent plaque rupture? II. Having non-MMPs proteases reported as significant player in atherosclerotic plaque, one would want to know which one to target, MMPs or non-MMPs? III. Knowing the unwanted results of MMP inhibitors in cancer trials, is there any hope for MMP trials in cardiovascular and vulnerable plaque field?
- 10. Suggestion: VP.org Editorial Suggestion: - Please email your thoughts to: Discussion-Group@VP.org or DG@VP.org
- 11. 1. Victor J. Ferrans; New Insights Into the World of Matrix Metalloproteinases; Circulation 2002 105: 405 - 407. 2. aaaGalis ZS. Metalloproteases in remodeling of vascular extracellular matrix. Fibrin Proteol. 1999;13:54–63. 3. Galis ZS, Asanuma K, Godin D, Meng X.; N-acetyl-cysteine decreases the matrix-degrading capacity of macrophage-derived foam cells: new target for antioxidant therapy? Circulation. 1998 Jun 23;97(24):2445-53. 4. Herman MP, Sukhova GK, Kisiel W, Foster D, Kehry MR, Libby P, Schonbeck U.Tissue factor pathway inhibitor-2 is a novel inhibitor of matrix metalloproteinases with implications for atherosclerosis. J Clin Invest. 2001 May;107(9):1117-26. 5. aHerman MP, Sukhova GK, Libby P, Gerdes N, Tang N, Horton DB, Kilbride M, Breitbart RE, Chun M, Schonbeck U.Expression of neutrophil collagenase (matrix metalloproteinase-8) in human atheroma: a novel collagenolytic pathway suggested by transcriptional profiling.Circulation. 2001 Oct 16;104(16):1899- 904. 6. aaaRekhter MD, Hicks GW, Brammer DW, Hallak H, Kindt E, Chen J, Rosebury WS, Anderson MK, Kuipers PJ, Ryan MJ. Hypercholesterolemia causes mechanical weakening of rabbit atheroma: local collagen loss as a prerequisite of plaque rupture. Circ Res. 2000;86:101–108. 7. Galina K. Sukhova, Guo-Ping Shi, Daniel I. Simon, Harold A. Chapman, and Peter LibbyExpression of the elastolytic cathepsins S and K in human atheroma and regulation of their production in smooth muscle cells. J Clin Invest. 1998 References
- 12. 8. Aikawa M, Rabkin E, Sugiyama S, Voglic SJ, Fukumoto Y, Furukawa Y, Shiomi M, Schoen FJ, Libby P. An HMG-CoA Reductase Inhibitor, Cerivastatin, Suppresses Growth of Macrophages Expressing Matrix Metalloproteinases and Tissue Factor In Vivo and In Vitro. Circulation. 2001 Jan 16;103(2):276-283. 9. Statins Alter Smooth Muscle Cell Accumulation and Collagen Content in Established Atheroma of Watanabe Heritable Hyperlipidemic Rabbits Yoshihiro Fukumoto, Peter Libby, Elena Rabkin, Christopher C. Hill, Makoto Enomoto, Yasuhiko Hirouchi, Masashi Shiomi, and Masanori Aikawa Circulation 2001 103: 993 - 999. 8. Loftus IM, Naylor AR, Bell PR, Thompson MM; Related Articles Plasma MMP-9 - a marker of carotid plaque instability. Eur J Vasc Endovasc Surg. 2001 Jan;21(1):17-21. 11. Tom W.G. Carrell, Kevin G. Burnand, Graham M.A. Wells, John M. Clements, and Alberto Smith Stromelysin-1 (Matrix Metalloproteinase-3) and Tissue Inhibitor of Metalloproteinase-3 Are Overexpressed in the Wall of Abdominal Aortic Aneurysms; Circulation 2002 105: 477 - 482. 12. Pyo R, Lee JK, Shipley JM, Curci JA, Mao D, Ziporin SJ, Ennis TL, Shapiro SD, Senior RM, Thompson RW Targeted gene disruption of matrix metalloproteinase-9 (gelatinase B) suppresses development of experimental abdominal aortic aneurysms.J Clin Invest. 2000 Jun;105(11):1641-9. References