Epigenetic studies have identified DNA methylation in coronary artery disease (CAD). How the critical genes interact at the cellular level to cause CAD is still unknown. The discovery of DNA methylation inspired researchers to explore relationships in genomic coding and disease phenotype. In the past two decades, there have been many findings regarding the relationship between DNA methylation and CAD development, and the DNA methylation of critical genes have been found to be significantly changed during CAD, including DNA methylation at homocysteine, Alu and long Interspersed Element 1 (LINE-1) repetitive elements.
Dna methylation ppt
definition of Dna methylation ppt
discovery of Dna methylation ppt
types of Dna methylation ppt
history of Dna methylation ppt
process of Dna methylation ppt
mechanism of Dna methylation ppt
methylation in cancer
cytosine methylation
genomic imprinting
The epigenetic regulation of DNA-templated processes has been intensely studied over the last 15
years. DNA methylation, histone modification, nucleosome remodeling, and RNA-mediated targeting regulate many biological processes that are fundamental to the genesis of cancer. Here, we
present the basic principles behind these epigenetic pathways and highlight the evidence suggesting that their misregulation can culminate in cancer. This information, along with the promising clinical and preclinical results seen with epigenetic drugs against chromatin regulators, signifies that it
is time to embrace the central role of epigenetics in cancer.
Dna methylation ppt
definition of Dna methylation ppt
discovery of Dna methylation ppt
types of Dna methylation ppt
history of Dna methylation ppt
process of Dna methylation ppt
mechanism of Dna methylation ppt
methylation in cancer
cytosine methylation
genomic imprinting
The epigenetic regulation of DNA-templated processes has been intensely studied over the last 15
years. DNA methylation, histone modification, nucleosome remodeling, and RNA-mediated targeting regulate many biological processes that are fundamental to the genesis of cancer. Here, we
present the basic principles behind these epigenetic pathways and highlight the evidence suggesting that their misregulation can culminate in cancer. This information, along with the promising clinical and preclinical results seen with epigenetic drugs against chromatin regulators, signifies that it
is time to embrace the central role of epigenetics in cancer.
Epigenetics definition, history of epigenetics, molecular basis of epigenetics, epigenetic modification, tools to study epigenetics, disease linked with epigenetics, DNA methylation demethylation and enzymes regulating DNA methylation
Epigenetics definition, history of epigenetics, molecular basis of epigenetics, epigenetic modification, tools to study epigenetics, disease linked with epigenetics, DNA methylation demethylation and enzymes regulating DNA methylation
Cardiomyopathies are heart muscle diseases originated from a series of aggressions, such as genetic defects, cardiac myocyte injury or infiltration of myocardial tissue. Dilated cardiomyopathy (DCM) is characterized by an impairment of the left ventricular or biventricular contraction, caused by familial, genetic, viral, autoimmune, alcoholic, toxic, or of unknown cause.
Cancer Epigenetics: Concepts, Challenges and PromisesMrinmoy Pal
The presentation highlights how recent investigations have shown extensive reprogramming of almost every component of the epigenetic machinery in cancer leading to the emergence of the promising field of epigenetic therapy.
Functional genomics has led to an improvement of our understanding of CVD and can be translated to clinical utility. Gene-based pre-symptomatic prediction of illness, finer diagnostic sub-classifications and improved risk assessment tools will permit earlier and more targeted intervention. Pharmacogenetics will guide our therapeutic decisions and monitor response to therapy. Personalised medicine requires the integration of clinical information, stable and dynamic genomics and molecular phenotyping.
It is now possible to systematically search the entire human genome for common variants that are associated with a particular phenotype. (HGP, HAP MAP)
Recent Trends in Genomic Biomarkers - Pepgra HealthcarePEPGRA Healthcare
Cardiovascular disease is a significant health concern worldwide despite having many genomics developments providing valuable new candidates for better biomarkers and novel therapeutic targets. The main integration of new technologies promises the discovery and validation of better biomarkers of the presence of cardio disease, its progression, and the response to treatment in this blog. Some of the features are:
1. Analyzing the Gene expression
2. Genome-wide association studies
3. Linkage analysis
4. Wrapping up...
Continue Reading: http://bit.ly/3bqq3Np
Contact us:
UK: +44-1143520021
US/Canada: +1-972-502-9262
India: +91-9884350006
Email id: sales.cro@pepgra.com
Website: www.pepgra.com
Recent trends in genomic biomarkers pepgra healthcarePEPGRA Healthcare
Cardiovascular disease is a significant health concern worldwide despite having many genomics developments providing valuable new candidates for better biomarkers and novel therapeutic targets. The main integration of new technologies promises the discovery and validation of better biomarkers of the presence of cardio disease, its progression, and the response to treatment in this blog. Some of the features are:
1. Analyzing the Gene expression
2. Genome-wide association studies
3. Linkage analysis
4. Wrapping up...
Continue Reading: http://bit.ly/3bqq3Np
Contact us:
UK: +44-1143520021
US/Canada: +1-972-502-9262
India: +91-9884350006
Email id: sales.cro@pepgra.com
Website: www.pepgra.com
DNA Methylation and Epigenetic Events Underlying Renal Cell Carcinomaskomalicarol
Renal cell carcinoma (RCC) refers to a group of tumors that develop from the epithelium of the kidney tubes, including clear cell
RCC, papillary RCC, and chromophobe RCC. Most clear cell renal
carcinomas have a large histologic subtype, genetic or epigenetic
genetic von Hippel-Lindau (VHL). A comprehensive analysis of
the genetic modification genome suggested that chromosome 3p
loss and chromosome gains 5q and 7 may be a significant copy
defect in the development of clear kidney cell cancer. A more potent renal cell carcinoma may develop if chromosome 1p, 4, 9,
13q, or 14q is also lost. Renal carcinogenesis is not associated with
chronic inflammation or histological changes. However, regional hypermethylation of DNA in CpG C-type islands has already
accumulated in cancer-free kidney tissue, implying that the presence of malignant kidney lesions may also be detected by modified
DNA methylation. Modification of DNA methylation in cancerous
kidney tissue may advance kidney tissue to epigenetic mutations
and genes, leading to more serious cancers and even determining
a patient’s outcome
Similar to The Role of DNA Methylation in Coronary Artery Disease (20)
Koroner Arter Hastalığında DNA Metilasyonunun RolüBardia Farivar
Epigenetik çalışmalar, koroner arter hastalığında (CAD) DNA metilasyonunu tanımlamıştır. Kritik genlerin hücresel düzeyde CAD'ye neden olarak nasıl etkileştiği hala bilinmemektedir.
DNA metilasyonunun keşfi, araştırmacıları genomik kodlama ve hastalık fenotipindeki ilişkileri araştırmaya teşvik etti.
Son yirmi yılda, DNA metilasyonu ve CAD gelişimi arasındaki ilişki hakkında birçok bulgu olmuştur.
Kritik genlerin DNA metilasyonunun, homosistein, Alu ve Long interspersed nuclear elements 1 (LINE-1) DNA metilasyonu dahil, CAD sırasında önemli ölçüde değiştiği bulunmuştur.
The Janus kinase/Signal transducers and activators of transcription (JAK/STAT)
JAK/STAT sinyal yolu sitokinler tarafından aktifleştirilir.
Hücre farklılaşması
Hücre çoğalması
Hücre göçü
Apoptoz gibi birçok hücresel sürecin yönetilmesinde rolü vardır.
İmmün sistemi gelişimi, süt oluşumu, adipogenez gibi işlemlerin gerçekleştirilmesinde bu sinyal yolunun rolü vardır.
DNA'nın yapısı ve görevi hakkındaki önemli bilgiler 1947 yılında biyokimyacı Erwin Chargaff tarafından açıklanmıştır.
Chargaff, farklı organizmaların DNA'larının baz bileşimlerini analiz etmiş ve DNA'daki baz dizisinin türden türe değiştiğini keşfetmiştir.
1953 yılında Amerikalı James Watson ve İngiliz Francis Crick yaptıkları deneylerden ve önceki bulgularından yararlanarak DNA'nın çift sarmal modelini oluşturmuşlardır.
Mikroorganizmalar arasında gen klonlamasında bir çok aracı moleküllerden yararlanılmaktadır.
Gen klonlamasında kullanılan aracı moleküllere vektör denir.
Vektörler konakçı organizmada, bağımsız olarak replikasyon gösterirler.
Sistemik Lupus Eritematozus sebebi bilinmeyen cilt, eklem, böbrek, kalp zarı (perikard), akciğer zarı (plevra) gibi birçok doku ve organ iltihabına bağlı çok sayıda bulgularla giden, değişik seyir gösteren ve bağışıklık sisteminin bozuk çalışması sonucu ortaya çıkan bir hastalıktır.
DNA Mikroarray 'DNA çip', 'gen çip', 'genom çip', veya gen-dizi olarak da bilinen, genellikle her biri bir geni temsil eden, ayrı ayrı küçük katı yüzeye kovalent bağlarla sabitlenmiş binlerce DNA parçacıkları toplusudur.
Her DNA spotlarda 10-12 mol spesifik DNA sekansları bulunur ki “probe” yada oligo olarak bilinirler.
Bilinen her gen veya probe çip üzerinde belirli bir noktada oturup ve değişen seviyelerde floresan aktivitesi, dahil edilen genetik materyalde değişen seviyelerde gen aktivitesi gösterir.
Prob sekanslara bağlanan floresan etiketli hedef diziler bir sinyal üretir.
Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease. The immune system attacks the body’s cell and tissue, resulting in inflammation and tissue damage. SLE can affect any part of the body, but most often harms the heart, joints, skin, lungs, blood vessels, liver, kidney and nervous system.
Over 40 different genes predispose to SLE.
Characterized by remission and exacerbation.
The Rho family of GTPases is a family of small G proteins. The members of the Rho GTPase family have been shown to regulate many aspects of intracellular actin dynamics, and are found in all eukaryotic kingdoms, including yeasts and some plants.
This pdf is about the Schizophrenia.
For more details visit on YouTube; @SELF-EXPLANATORY;
https://www.youtube.com/channel/UCAiarMZDNhe1A3Rnpr_WkzA/videos
Thanks...!
This presentation explores a brief idea about the structural and functional attributes of nucleotides, the structure and function of genetic materials along with the impact of UV rays and pH upon them.
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...Sérgio Sacani
We characterize the earliest galaxy population in the JADES Origins Field (JOF), the deepest
imaging field observed with JWST. We make use of the ancillary Hubble optical images (5 filters
spanning 0.4−0.9µm) and novel JWST images with 14 filters spanning 0.8−5µm, including 7 mediumband filters, and reaching total exposure times of up to 46 hours per filter. We combine all our data
at > 2.3µm to construct an ultradeep image, reaching as deep as ≈ 31.4 AB mag in the stack and
30.3-31.0 AB mag (5σ, r = 0.1” circular aperture) in individual filters. We measure photometric
redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts
z = 11.5 − 15. These objects show compact half-light radii of R1/2 ∼ 50 − 200pc, stellar masses of
M⋆ ∼ 107−108M⊙, and star-formation rates of SFR ∼ 0.1−1 M⊙ yr−1
. Our search finds no candidates
at 15 < z < 20, placing upper limits at these redshifts. We develop a forward modeling approach to
infer the properties of the evolving luminosity function without binning in redshift or luminosity that
marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the
impact of non-detections. We find a z = 12 luminosity function in good agreement with prior results,
and that the luminosity function normalization and UV luminosity density decline by a factor of ∼ 2.5
from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical
models for evolution of the dark matter halo mass function.
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
Multi-source connectivity as the driver of solar wind variability in the heli...Sérgio Sacani
The ambient solar wind that flls the heliosphere originates from multiple
sources in the solar corona and is highly structured. It is often described
as high-speed, relatively homogeneous, plasma streams from coronal
holes and slow-speed, highly variable, streams whose source regions are
under debate. A key goal of ESA/NASA’s Solar Orbiter mission is to identify
solar wind sources and understand what drives the complexity seen in the
heliosphere. By combining magnetic feld modelling and spectroscopic
techniques with high-resolution observations and measurements, we show
that the solar wind variability detected in situ by Solar Orbiter in March
2022 is driven by spatio-temporal changes in the magnetic connectivity to
multiple sources in the solar atmosphere. The magnetic feld footpoints
connected to the spacecraft moved from the boundaries of a coronal hole
to one active region (12961) and then across to another region (12957). This
is refected in the in situ measurements, which show the transition from fast
to highly Alfvénic then to slow solar wind that is disrupted by the arrival of
a coronal mass ejection. Our results describe solar wind variability at 0.5 au
but are applicable to near-Earth observatories.
What is greenhouse gasses and how many gasses are there to affect the Earth.moosaasad1975
What are greenhouse gasses how they affect the earth and its environment what is the future of the environment and earth how the weather and the climate effects.
Richard's entangled aventures in wonderlandRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Cancer cell metabolism: special Reference to Lactate PathwayAADYARAJPANDEY1
Normal Cell Metabolism:
Cellular respiration describes the series of steps that cells use to break down sugar and other chemicals to get the energy we need to function.
Energy is stored in the bonds of glucose and when glucose is broken down, much of that energy is released.
Cell utilize energy in the form of ATP.
The first step of respiration is called glycolysis. In a series of steps, glycolysis breaks glucose into two smaller molecules - a chemical called pyruvate. A small amount of ATP is formed during this process.
Most healthy cells continue the breakdown in a second process, called the Kreb's cycle. The Kreb's cycle allows cells to “burn” the pyruvates made in glycolysis to get more ATP.
The last step in the breakdown of glucose is called oxidative phosphorylation (Ox-Phos).
It takes place in specialized cell structures called mitochondria. This process produces a large amount of ATP. Importantly, cells need oxygen to complete oxidative phosphorylation.
If a cell completes only glycolysis, only 2 molecules of ATP are made per glucose. However, if the cell completes the entire respiration process (glycolysis - Kreb's - oxidative phosphorylation), about 36 molecules of ATP are created, giving it much more energy to use.
IN CANCER CELL:
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
introduction to WARBERG PHENOMENA:
WARBURG EFFECT Usually, cancer cells are highly glycolytic (glucose addiction) and take up more glucose than do normal cells from outside.
Otto Heinrich Warburg (; 8 October 1883 – 1 August 1970) In 1931 was awarded the Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme.
WARNBURG EFFECT : cancer cells under aerobic (well-oxygenated) conditions to metabolize glucose to lactate (aerobic glycolysis) is known as the Warburg effect. Warburg made the observation that tumor slices consume glucose and secrete lactate at a higher rate than normal tissues.
4. An Overview of Sugarcane White Leaf Disease in Vietnam.pdf
The Role of DNA Methylation in Coronary Artery Disease
1. The Role of DNA Methylation in
Coronary Artery Disease
Bardia Farivar
Department of Medical Biology
Istanbul University
Cerrahpaşa Medical Faculty
2. Abstract:
• Epigenetic studies have identified DNA methylation in coronary
artery disease (CAD). How the critical genes interact at the cellular
level to cause CAD is still unknown. The discovery of DNA
methylation inspired researchers to explore relationships in
genomic coding and disease phenotype. In the past two decades,
there have been many findings regarding the relationship between
DNA methylation and CAD development, and the DNA methylation
of critical genes have been found to be significantly changed during
CAD, including DNA methylation at homocysteine, Alu and long
Interspersed Element 1 (LINE-1) repetitive elements.
3. • Over the past few decades, coronary artery disease (CAD)
has been among the leading cause of morbidity and
mortality worldwide. The number of deaths due to CAD is
56 million globally. CAD is caused by a variety of factors, in
which atherosclerosis is the main pathological basis of
CAD. Epigenetic factors, including DNA methylation,
histone modification, chromatin remodeling and noncoding
RNA regulation, have been reported to cause CAD by
altering the interaction between genes and the
environment.
4. 1. Introduction of DNA methylation
• DNA methylation refers to a covalent methylation
modification on the cytosine base of the 5’ CpG3’
dinucleotide, which is the major DNA modification in
mammals. Largely unmethylated CpG segments are named
CpG islands which always appear at the regions of
promoters. While, methylated CpGs are mainly located at
non-regulatory areas in the genome. CpG islands play an
extremely important role as a key regulatory region of DNA
transcription. Most of the methylated CpGs are established
and maintained by DNA methyltransferases (DNMTs), such
as DNMT3A, DNMT3B and DNMT3L.
5. Mechanism of DNA methylation on genes. In DNA
methylation, a methylation modification appears on
the cytosine base of the 5’ CpG3’ dinucleotide. If the
methylation of the gene is upregulated by DNMTs, the
structure of the DNA linked tightly so that the gene
cannot be transcribed.
6. 2. DNA Methylation in CAD
• In the past two decades, there have been many findings
regarding the relationship between DNA methylation
and CAD development. And the DNA methylation of
critical genes have been found to be significantly
changed during CAD. In cell and animal studies, the
common mode is to focus on a critical gene in CAD and
then examine the methylation of the critical gene or the
critical gene promoter. Generally, hypomethylation of
the gene promoter can upregulate expression of the
gene, while hypermethylation of the gene promoter can
downregulate expression of the gene.
7. • Average gene methylation level was inversely associated
with the expression of the gene. Another mode is to
observe the change of the phenotype with DNA
methylation inhibitor. In the human tissue studies,
genome-wide methylation was often applied between
CAD patients and control with Human Methylation
array or sequencing. Meanwhile, based on some
previous studies, the methylation of critical genes was
also detected in human tissue by pyrosequencing or
methylation specific PCR (MSP).
8. 3.1 The evidence from cell and animal
studies
• DNA methylation inhibits the functions of the critical
genes in CAD. Hypermethylation of the gene promoter
can downregulate expression of the gene. Aldehyde
dehydrogenase 2 (ALDH2) is important to protect
myocardium from ischemia. Hypermethylation of the
ALDH2 promoter inhibited ALDH2 after MI in border
zone tissues, which is related to myocardial ischemia. In
myocardial infarction (MI) rats, ALDH2 was
significantly downregulated. Meanwhile, DNA
methylation of the ALDH2 promoter increased
significantly time-dependently.
9. 3.1.1 Homocysteine
• Homocysteine (Hcy), a thiol amino acid, is also a key
modulator in DNA methylation. Hyperhomocysteinemia
(HHcy) is a candidate risk factor for CAD. Hcy is the
precursor of methionine, which could be converted to
S- adenosylmethionine (SAM). SAM is the main methyl
group donor in DNA methylation. In the process of
transferring the methyl group, SAM is converted to S-
adenosylhomocysteine (SAH). Therefore, Hcy is a bridge
between DNA methylation and CAD.
10. Methionine Cycle
• Hcy is the precursor of methionine, which could be
converted to S- adenosylmethionine (SAM). SAM is the
main methyl group donor in DNA methylation. In the
process of transferring the methyl group, SAM is converted
to S-adenosylhomocysteine (SAH).
11. 3.1.2 Atherosclerosis
• Currently, atherosclerosis is the major basis of CAD, and
DNA methylation play a role of atherosclerosis as DNA
methylation can inhibit the expression of critical genes
or gene promoters related to atherosclerosis. In addition,
recently, investigators have been identifying the
diagnostic value of DNA methylation in atherosclerosis.
12. • Estrogen receptor (ER) modulators benefit
cardiovascular outcomes and lipid improvements. In
1999 it was found that methylation inactivation of the
ER alpha in vascular tissue may play a role in
atherogenesis and the ageing of the vascular system.
Coronary atherosclerotic tissues exhibited higher levels
of methylation in human aorta samples using Human
Methylation 450k array. In swine aorta regions
susceptible to atherosclerosis, methylation of ATF4, the
ER stress gene appears differentially, as well as
microRNA-10a. In addition, DNMTs and methylation of
ER alpha was recruited by insulin so that ER alpha, the
regulator of VSMCs proliferation, decreased to result in
atherosclerosis both in vitro and in vivo.
13. 3.2 The evidence from human tissue studies
• Recently, studies on DNA methylation related to CAD
begin to expand rapidly from cell or animal experiments
to epidemiological research. In CAD or atherosclerosis
patients, genome-wide DNA methylation was examined
to find the critical genes and sequences, such as ABCA1,
DDAH2, LINE-1 and Alu. Different genetic, lifestyle and
environmental factors may affect DNA methylation,
CAD and its risk factors.
14. 3.2.1 CAD
• Genome-wide DNA methylation was often determined in blood
samples of CAD patients and controls with Human
Methylation array. Immune signaling and cellular functions
might be regulated at an epigenetic level in acute coronary
syndrome (ACS) patients. Genome-wide DNA methylation of
whole blood was detected in 102 ACS patients and 101 controls
using Human Methylation 450 array and another replicated
cohort of 100 patients and 102 controls, a significant
enrichment of CpGs was validated again related with smoking
and low-density lipoprotein cholesterol (LDL-C) in T and B
cells.
15. • . The results could be identified twice. In addition, it
indicated DNA methylation could have different
meanings in different cells from the blood of human. In
the same method, another study included a total of 192
subjects with MI and 192 control subjects. Three DNA
methylation sites showed genome-wide significant
associations with MI. Two of these sites still showed
such associations after adjustment for classical risk
factors of MI.
16. • The study provided a potential biomarker for MI. In
addition, among individuals with a history of MI, DNA
methylation appeared deviated. In 729 blood samples
from the northern Sweden population health study,
differential DNA methylation was observed at 211 CpG-
sites in individuals with a history of MI. These sites
represent 196 genes, of which 42 have been described to
be associated with cardiovascular disease. Interestingly,
DNA methylation at specific loci was associated with the
risk of MI in women which is sensitive to prenatal
conditions. No association was observed among men.
17. • Global DNA methylation was positively correlated with
plasma Hcy levels of CAD patients. DNA methylation
was evaluated in a cohort of 137 CAD patients and 150
controls. Significantly higher levels of serum Hcy and
global DNA methylation was observed in CAD
patients[42]. A total of 72 differentially methylated
regions (DMRs) were hypermethylated in CAD patients
with varying Hcy levels
18. • DDAH2 is an enzyme found in all mammalian cells.
DDAH2 degrades methylarginines, specifically
asymmetric dimethylarginine (ADMA).
• Hypermethylation in the DDAH2 promoter was
positively correlated with EPCs dysfunction in CAD
patients. Hcy disrupted EPCs function by inducing the
hypermethylation of the DDAH2 promoter[46]. The
plasma levels of ADMA had been proved to be an
independent cardiovascular risk factor.
19. • Inflammation is the critical factor in CAD and
atherosclerosis. Interleukin-6 (IL-6) is a multifunctional
cytokine in inflammation. Methylation at two CpG sites
in IL-6 promoter was measured by pyrosequencing in
blood leukocyte of a total of 212 cases with CAD and 218
controls. Mean methylation level in IL-6 promoter in
CAD cases was significantly lower, inversely associated
with the risk of CAD.
20. 3.2.2 Atherosclerosis
• With the HumanMethylation array, hypomethylation of
these sites appeared in leukocytes and atherosclerotic
arteries. In addition, several cardiovascular disease risk
factors, as well as medications, might affect methylation
levels of CpG sites. In the same way, a large-scale
analysis of DNA methylation in subjects with
atherosclerosis has indicated that aberrant DNA
methylation in subjects with atherosclerosis affects the
transcription of critical regulatory genes to induce a pro-
atherogenic cellular phenotype.
21. 3.3 The intervention via DNA methylation
• Several experiments have reported that drugs or foods elicit a therapeutic
effect via the methylation of specific genes. For example:
The intake of aspirin, a conventional drug in the established guidelines, leads to
significantly increased L5 levels in STEMI patients. With low concentration aspirin, L5
impairment of HCAEC function was inhibited through CpG methylation at the FGF2
promoter.
The Western-type diet could induce transplantable epigenetic changes in bone marrow
cells, alter the haematopoietic system, and increase the susceptibility to atherosclerosis
Bvitamins intake was negatively associated with DNA-methylation of the candidate
genes. folate and B-vitamins low intake may regulate methylation in critical enzymes of
One-Carbon metabolism and Hcy related to the CAD risk.
• Therefore, DNA methylation could become a therapeutic target for the
prevention and treatment of CAD.
22. 4. Conclusion
DNA methylation is a key epigenetic process in CAD.
DNA methylation patterns exhibit different in different
tissues, genes and gene promoters among CAD patients.
Hcy, a thiol amino acid, plays a critical role in DNA
methylation among CAD patients and is as an independent
risk factor for cardiovascular disease as well as a key
modulator of macromolecular methylation.
The Alu and LINE-1 element sequences are potential
markers for DNA methylation in CAD patients.
DNA methylation also influences atherosclerosis in several
aspects and CAD risks.
DNA methylation of specific genes can play important roles
in the early diagnosis of CAD and atherosclerosis.
This reveals the potential effect of DNA methylation on
CAD.