The document analyzes the expression of sex hormone receptors in abdominal aortic aneurysms (AAA). It finds that the expression of the androgen receptor (AR) is higher in AAA tissue compared to unaffected aortic tissue, while the expression of estrogen receptor beta (ERβ) is lower. The expression profile of sex hormone receptors is similar in men and women with AAA. This suggests that sex hormone activity may be associated with aneurysm development, with higher AR expression and lower ERβ expression playing a role.
Impact of percutaneous coronary intervention on the levels of interleukin-6 and C-reactive protein in the coronary circulation of subjects with coronary artery disease
Extracorporeal membrane oxygenation assisted cardiopulmonary resuscitation (ECPR) is an effective therapy to improve outcomes for children who experience cardiopulmonary arrest. Survival after ECLS varies between 60% and 75%. For ECPR survival is lower, with 40% to 50% of children surviving ECPR. After ECPR good neurological outcomes are seen in 40% to 60% of children. This contrasts with adult patients where neurological outcomes after ECPR are poor. Given these findings the American Heart Association has included ECPR in their 2015 guidelines for children who experience an in hospital cardiac arrest (IHCA).
Presentation delivered by Dr Steven M. Fruchtman, Chief Medical Officer, Onconova Therapeutics at the marcus evans Evolution Summit Spring 2017 held at the Ritz-Carlton Coconut Grove, FL, May 8-10.
Impact of percutaneous coronary intervention on the levels of interleukin-6 and C-reactive protein in the coronary circulation of subjects with coronary artery disease
Extracorporeal membrane oxygenation assisted cardiopulmonary resuscitation (ECPR) is an effective therapy to improve outcomes for children who experience cardiopulmonary arrest. Survival after ECLS varies between 60% and 75%. For ECPR survival is lower, with 40% to 50% of children surviving ECPR. After ECPR good neurological outcomes are seen in 40% to 60% of children. This contrasts with adult patients where neurological outcomes after ECPR are poor. Given these findings the American Heart Association has included ECPR in their 2015 guidelines for children who experience an in hospital cardiac arrest (IHCA).
Presentation delivered by Dr Steven M. Fruchtman, Chief Medical Officer, Onconova Therapeutics at the marcus evans Evolution Summit Spring 2017 held at the Ritz-Carlton Coconut Grove, FL, May 8-10.
Methods: The current clinical study was conducted at Gaza city. It involved 90 patients who were scheduled for coronary angioplasty procedure. The patients were divided into three groups: The first group (n = 30), underwent BMS implantation and received colchicine 0.5 mg twice daily for six months. The second group (n = 30), underwent BMS implantation alone. The third group (n = 30) underwent DES implantation. All the patients were followed up for six months. The primary endpoint was clinical ISR at 6months. Secondary endpoints included Target Vessel Revascularization (TVR) and Stent Thrombosis (ST).
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Estrogen and Progesterone Receptors Expression in Resected Gallbladder from Gall bladder Carcinoma Cases-Gallbladder carcinoma is most common malignancy of gartrointestinal tract (GIT) with poor diagnosis. Its prevalence is higher in females that too of northern India. This study aimed to identify the role of sex hormones in carcinoma gallbladder (CA GB). Resected 100 gall bladders of CA GB were examined immune-histo-chemicaly to find out ER and PR status with its association with its underlying histopathology. It was found in this study that PR status was observed in 36% of cases whereas ER status was positive in 2% of CA GB cases. It was also revealed that ER expression was specific and PR expression was more sensitive indicator in differentiating between benign and malignant carcinoma gall bladder.
Austin Journal of Clinical & Diagnostic Research is a multidisciplinary, Rapid-Publication journal. Austin Journal of Clinical & Diagnostic Research Journal is open to scientists from all countries. The mission of the journal is to promote topics of Clinical & Diagnostic research, as well as stimulate international cooperation in these areas. The journal will consider articles from every legitimate specialty.
Austin Publishing Group's mission to facilitate immediate access to scientific data through an Open Access platform is greatly supported by invaluable contributions from the strong editorial and advisory boards.
Austin Publishing Group is moving ahead with a vision to develop an optimized knowledge sharing platform and an enlightening interactive network for researchers all over the world through its scientific publications and meetings.
Introduction:
RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is an important biological process for modulating eukaryotic gene expression.
It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences.
dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants.
This process mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes.
What are small ncRNAs?
micro RNA (miRNA)
short interfering RNA (siRNA)
Properties of small non-coding RNA:
Involved in silencing mRNA transcripts.
Called “small” because they are usually only about 21-24 nucleotides long.
Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered).
Silence an mRNA by base pairing with some sequence on the mRNA.
Discovery of siRNA?
The first small RNA:
In 1993 Rosalind Lee (Victor Ambros lab) was studying a non- coding gene in C. elegans, lin-4, that was involved in silencing of another gene, lin-14, at the appropriate time in the
development of the worm C. elegans.
Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14.
Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions.
Types of RNAi ( non coding RNA)
MiRNA
Length (23-25 nt)
Trans acting
Binds with target MRNA in mismatch
Translation inhibition
Si RNA
Length 21 nt.
Cis acting
Bind with target Mrna in perfect complementary sequence
Piwi-RNA
Length ; 25 to 36 nt.
Expressed in Germ Cells
Regulates trnasposomes activity
MECHANISM OF RNAI:
First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces.
Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands.
The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it.
THE RISC COMPLEX:
RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA
Unwinding of double stranded Si RNA by ATP independent Helicase
Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA.
DICER: endonuclease (RNase Family III)
Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC)
One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute
ARGONAUTE PROTEIN :
1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA
2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity.
MiRNA:
The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .
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.
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.
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.
A brief information about the SCOP protein database used in bioinformatics.
The Structural Classification of Proteins (SCOP) database is a comprehensive and authoritative resource for the structural and evolutionary relationships of proteins. It provides a detailed and curated classification of protein structures, grouping them into families, superfamilies, and folds based on their structural and sequence similarities.
2. 40 C. Villard et al. / Maturitas 96 (2017) 39–44
observed when the recipient was female was lost if the recipient
instead was male [15].
Studies on the potential effect of gender on aneurysm devel-
opment in humans are scarce. The observed negative association
between AAA occurrence and long-term hormone therapy and the
lower menopausal age in women with larger AAA support the the-
ory of a protective effect of female sex hormones [16,17]. On the
other hand, lower levels of testosterone are associated with AAA
occurrence in elderly men [18].
Studies on gender aspects on aneurysm formation primarily
focus on an effect of endogenous as well as exogenous sex hor-
mones and little is known about the expression profile of sex
hormone receptors in the aneurysm wall [12,15,18,19]. The aim of
this study was to examine the expression profile of the sex hormone
receptors: ER␣, ER, progesterone receptor (PR) and androgen
receptor (AR) in the aneurysmal walls of men and women and com-
pare with the expression profile in non-aneurysmal aortic walls.
The study focused on the medial layer of the aortic vessel wall as it
is most affected by degradation in aneurysm development [20].
2. Material and method
2.1. Study population and tissue handling
All women treated electively for AAA with open repair (OR)
at Karolinska University Hospital, Stockholm Sweden, November
2008–June 2014, were included (n = 16). Male patients treated
during the same time period (n = 16), were chosen to match the
age and aneurysm diameter of the participating women. Mycotic
aneurysms were not included. The patients were treated with OR,
as they were considered unsuitable for endovascular aneurysm
repair (EVAR). Biopsies of the ventral, infrarenal aneurysm wall,
at the maximum diameter, were obtained during the surgical pro-
cedure. Only thrombus covered aneurysm walls were used since
non-thrombus covered aneurysm walls could not be obtained from
all participants, which is probably due to the low occurrence
of thrombus free walls in such large aneurysms. Patient char-
acteristics were obtained from hospital charts. Body mass index
(BMI) was defined as the ratio of weight/square of the height
[21]. Body surface area (BSA) was predicted using DuBois formula:
(weight0.425xheight0.725) × 0.007184 [22]. Aortic size index (ASI)
was defined as the ratio of aneurysm diameter/BSA [23]. All patients
had signed an informed consent prior to the surgical procedure.
The control group consisted of 6 organ donors, male and female.
The aortic diameters of the organ donors were not measured, but
defined non-aneurysmal by the transplant surgeon. During the
organ donation biopsies of the infrarenal aorta were obtained. The
aortic biopsies from organ donors and patients with AAA were han-
dled according to the same protocol and stored during transport
in RNAlater and formalin. The aortic walls, both aneurysmal and
non-aneurysmal, were divided into initimal, medial and advential
layers. The biopsies from organ donors could not be transported
freshly frozen, which limited the protein expression analysis. All
donors, or their close relatives, had signed an informed consent
regarding donation of the tissue for research purposes. Patient
characteristics were obtained from a form filled out by the organ
coordinator in charge and based on information from hospital
charts and from the patients’ relatives. The study was approved
by the local Ethics Committee.
2.2. Immunohistochemical analysis
5 m sections of aortic walls were deparaffinised in Tissue-
Clear (Sakura) and rehydrated in ethanol. The sections were boiled
under high pressure in DIVA-buffer (BioCare Medical) and Back-
ground Sniper Solution (BioCare Medical) was used for background
blocking. Antibodies ER (Thermo), PR (Dako) and AR (Dako) were
diluted in DaVinci Green Solution (BioCare Medical) for 60 min
in room temperature, followed by short incubations with Probe
and –Polymer Kit specific for mouse/rat (BioCare Medical). Vulcan
Fast Red Solution (BioCare Medical) was used for detection and
counterstaining was performed with Mayer’s hematoxillin (Vec-
tor Laboratories). Double staining with ER and smooth muscle
␣-actin (Abcam) were performed in a similar manner but with a
double staining probe and polymer Kit (BioCare Medical) and Warp
Red Solution together with Vine Green (Biocare Medical) for detec-
tion. Double stainings with AR and smooth muscle ␣-actin and PR
and smooth muscle ␣-actin were unfortunately not possible and
therefore the stainings were performed on consecutive sections.
2.3. mRNA expression analysis
Frozen medial layers of aortic walls were homogenized with
tissue lyser (Qiagen). RNA was isolated with Qiazol (Qiagen), RLT
buffer (from Rneasy Mini kit, Qiagen) and Dnase1 (Rnase free Dnase
Set, Qiagen) according to a standardized protocol. RNA was quanti-
fied by a Nanodrop (NanoDrop Products). RNA quality and integrity
were verified using the Agilent 2100 Bioanalyzer System (Agilent
Technologies). For quantification of gene expression, total RNA was
reversely transcribed to cDNA using High capacity RNA to cDNA
kit (Life technologies) the manufacturers protocol. Real time PCR
was performed on the Applied Biosystems 7000 Real-Time PCR Sys-
tem with TaqMan Assays-on-Demand Gene Expression Probes for
ER␣, ER, PR and AR. Robust multiarray average normalization was
performed and gene expression data were log2-transformed. The
housekeeping gene Ribosomal Protein Large P0 (RPLP0) was used
for normalization.
2.4. Western blot analysis
The medial layers of the aneurysm samples were shred and
mixed with a lysis buffer containing 50 l protease inhibitor and
30 l 1 M Tris-HCl pH 8,0. The mixture of samples and lysis buffer
samples were then granulated with a Tissuelyzer according to
manufacturer’s protocol and centrifuged for 5 min at 220 rpm. The
supernatants were sonicated for 5 min at high level followed by
centrifugation for 10 min at 12000 rpm. The protein content in the
supernatants was determined using Bradford protein assay. The
samples were diluted with lysis buffer before being loaded on a
4–12% SDS gel (Novex NuPAGE 4–12% Bis-Trisgel 15well, Invit-
rogen) in MOPS-SDS running buffer. Electrophoresis was run for
90 min at 120 V, in a cold room. The gel and membrane (Hybond
PVDF transfer membrane, GE Healthcare) were equilibrated in
transfer buffer before transfer by electroblotting for 90 min at
400 mA, in a cold room. For blocking, the membrane was suspended
in blocking buffer (3% bovine serum albumin/TTBS) for 60 min.
The membrane was incubated over night with ER (Thermo), AR
(Abcam) and GAPDH (Abcam) followed by the second antibody
(anti-Mouse and anti-Rabbit HRP, BioRab) for 45 min. Finally, the
developing solution from ECL Prime Western Blotting Detection
Reagent kit (GE Healthcare) and CCD camera (Fujifilm LAS-1000)
were used for chemiluminescent detection.
2.5. Statistical analysis
Statistical analysis was performed with SPSS 21.0. Independent
t-test was used for gender comparisons of normally distributed data
and Mann U test for not normally distributed data. Pearson’s chi-
square test and Fischer’s exact test were used for normally and not
normally distributed categorical variables, respectively. AAA occur-
rence and AAA diameter were estimated by multivariate logistic
3. C. Villard et al. / Maturitas 96 (2017) 39–44 41
Table 1
Patient characteristics.
Patients with AAA n = 32 Controlsn = 6 P-value
men women P-value
Age 69 ± 5 71 ± 7 0.327 72± 5 0.448
BMIa
25.6 ± 3.2 25.8 ± 4.0 0.899 26.0 ± 5.1 0.992
BSAb
1.9 ± 0.2 1.7 ± 0.2 0.004 1.8 ± 0.3 0.998
Aneurysm diameter (cm) 5.8 (.7) 5.7 (.6) 0.867 – –
ASIc
3.1 (.6) 3.5 (.5) 0.008 – –
Smoking habits (%) .380 0.001
Current 5 (31) 3 (9) 1 (17)
Prior 11 (69) 12 (75) 1 (17)
Never 0 1 (6) 4 (17)
High blood pressured
11 (69) 10 (63) .500 4 (67) 0.672
Heart conditione
3 (19) 3 (19) .673 0 (0) 0.328
Lung diseasef
3 (19) 3 (19) .673 1 (17) 0.698
Diabetes mellitus 3 (19) 0 0.113 0 0.588
Values are presented as mean ± standard deviation for normally distributed data and median (range) for not normally distributed data. Categorical variables are presented
as number (percent).
a
BMI – body mass index.
b
BSA – body surface area = (weight425
× height725
) × 0.007184.
c
ASI – aortic size index = aneurysm diameter/BSA.
d
High blood pressure – antihypertensive medication.
e
Heart condition – prior coronary bypass surgery, arterial fibrillation and/or heart failure.
f
Lung disease – chronic obstructive pulmonary disease and/or asthma.
and linear regression, respectively. The data was analysed using
a univariate model (sex, age, hypertension, heart condition, lung
disease, diabetes mellitus, smoking habits, BMI, ASI, ER␣, ER, PR
and AR were included) and clinically relevant variables or those
significant from the univariate analysis were analysed using a mul-
tiregression model. Statistical significance was defined as P < 0.05.
3. Results
3.1. Patient characteristics
Age, BMI as well as BSA were similar in patients with AAA and
controls (69 years vs. 70, P = 0.496, 25.7 vs. 26.0, P = 0.873 and 1.8 vs.
1.8, P = 0.987, respectively). Occurrence of comorbid conditions was
similar in patients with AAA and controls (Table 1)(Supplementary
Table I). Patients with AAA were prior and current smokers to a
greater extent than the control group, 25% vs. 17% and 72% vs. 17%,
P = 0.001.
Mean age of and aneurysm diameter in men and women with
AAA were similar (Table 1). Women with AAA had lower BSA
and higher ASI compared with men (Table 1). Smoking habits and
comorbid conditions were similar in men and women with AAA.
3.2. mRNA expressions of sex hormone receptors
Patients with AAA had higher mRNA expression levels of AR
and PR than controls (7.26 vs. 5.14, P = 0.001 and 8.73 vs. 6.21,
P = 0.003, respectively) (Table 2). mRNA expression of ER was
lower in patients with AAA compared with controls (9.15 vs. 12.29,
Table 2
mRNA expression levels of sex hormone receptors in patients with AAA and controls.
Patients with AAA
n = 32
Controls
n = 6
P-value
Estrogen receptor ␣ 5.92 ± 0.75 6.47 ± 0.30 0.090
Estrogen receptor  9.15 ± 1.45 12.29 ± 1.06 < 0.001
Progesterone receptor 8.73 (1.68) 6.21 (1.42) 0.003
Androgen receptor 7.26 ± 1.33 5.14 ± 0.51 0.001
Values, normalized to RPLP0, are presented log2-transformed and as arbitrary units.
Values are presented as mean ± standard deviation for normally distributed data and
median (range) for not normally distributed data.
P < 0.001) (Table 2). There was no difference in expression levels of
ER␣ between aneurysms and control aortas (Table 2).
Men and women with AAA did not differ regarding mRNA
expression levels of sex hormone receptors (Supplementary Table
II). No correlations were found between aneurysm size and mRNA
expression levels of sex hormone receptors.
A multiple logistic regression was calculated to predict AAA
occurrence in the study population based on: sex, age, hyper-
tension, diabetes mellitus, heart condition, lung disease, smoking
habits, BMI, BSA, expression levels of ER␣, ER, PR and AR. A sig-
nificant regression equation was found (F(1,36) = 25.336, P < 0.001),
with an R2 of 0.413 identifying the expression level of ER as a sig-
nificant predictor of AAA occurrence. A multiple linear regression
was calculated to predict AAA diameter in patients with AAA. A sig-
nificant regression equation was found (F (2,28) = 15.316, P < 0.001)
with an R2 of 0.488 identifying both ASI and heart condition as
significant predictors of AAA diameter.
3.3. Protein expressions of sex hormone receptors
Protein expression of ER in vascular smooth muscle cells
was lower in patients with AAA compared with controls, whereas
expression of AR was higher in patients with AAA compared with
controls, assessed by immunohistochemistry (Fig. 1). There was no
difference in the expression of PR between patients with AAA and
controls.
Protein expressions of ER and AR were similar in men and
women with AAA, assessed by western blot analysis (Fig. 2).
4. Discussion
The observed gender differences in aneurysm development
have been ascribed to effects of sex hormones on the vasculature,
yet to our knowledge this is the first study to investigate the expres-
sion profile of sex hormone receptors in human AAA. The results
show differences in the expression profile of sex hormone receptors
between aneurysmal and non-aneurysmal aortic walls, indepen-
dent of gender. The observed lower expression of ER and higher
expression of AR in aneurysms, could suggest that an increase of
AR and a decrease of ER are associated with the development of
AAA.
4. 42 C. Villard et al. / Maturitas 96 (2017) 39–44
Fig. 1. Double staining of ER (red) and smooth muscle ␣-actin (green) of (a) unaffected aorta and (b) aneurysmatic aorta. Medial layer enlarged. (For interpretation of the
references to colour in this figure legend, the reader is referred to the web version of this article.)
Staining on consecutive sections for AR (c) unaffected aorta, (e) aneurysmatic aorta and smooth muscle ␣-actin (d) unaffected aorta, (f) aneurysmatic aorta. Medial layer
enlarged.
The expression of sex hormones and the vascular effects that
they mediate are influenced by sex, age and menopause, which
could partly explain the lack of differences between the sexes in this
study [24,25]. Thereto, for apparent reasons, tissue from aneurysms
can only be obtained when patients are subjected to OR, which limit
the analysis to an end-stage disease. Since AAA affects an elderly
population it is also for practical reasons impossible to obtain biop-
sies of younger AAA patients, i.e. premenopausal women. With the
aid of results from studies on animals, we can only speculate on the
hormonal changes occurring in the aneurysm wall as AAA evolves
in men and women.
Estrogen receptors play an intricate role in many physiological
processes in the vasculature by modulating vascular tone, inflam-
matory response and smooth muscle cell proliferation [26,27]. ER␣
and ER are present in equal quantities in the aortic vascular
smooth muscle cells (VSMCs) of men, whereas ER is the primary
estrogen receptor in the aortic VSMCs of women [25]. The preven-
tive effect of exogenous estrogen on aneurysm development shown
in animal models is associated with an inhibition of the proteolytic
activity mediated by matrix metalloproteinases [12,15,19]. In this
study we found a lower expression of ER, mRNA and protein,
in aneurysmal media compared with unaffected media. We found
Fig. 2. Western blot analysis and densitometry of ER in the thrombus covered aneurysm wall of 5 men and 5 women (1.47 vs. 1.12, P = 0.841). Loading control: GAPDH.
5. C. Villard et al. / Maturitas 96 (2017) 39–44 43
no difference in the expression of ER␣ between aneurysmal and
non-aneurysmal tissue. It could suggest that a loss of a potentially
protective effect, mediated by ER, is associated with aneurysm
development in women.
The higher prevalence of AAA in men, even after adjustment for
risk factor distribution, suggests a susceptibility to aneurysm for-
mation dependent on male sex [5]. In animal models, AR has been
shown to induce aneurysm formation in mice by modulating the
inflammatory response and influencing the contractile response
of the vessel [28,29]. The finding of a higher expression of AR in
AAA compared with unaffected aorta could suggest an association
between aneurysm formation and the expression of AR. Further
studies are required to investigate a potential causation.
PR is expressed in VSMCs in a greater extent in pre- and post-
menopausal women compared with men, without correlation to
circulating levels of progesterone [30]. Polymorphisms of ER and
PR have been associated with AAA [31]. The effect of progesterone
on the vasculature is contradictory. The adverse events observed
in the WHI- and HERS trials have partly been ascribed to a pro-
thrombotic effect of medroxyprogesterone [32]. On the other hand
progesterone inhibits VSMC proliferation and thereby mediates
an antiatherogenic effect in cultured VSMCs and animal models
[33,34]. We found higher mRNA expression levels of PR in aneurys-
matic aortic walls compared with the unaffected aortic walls but
could not confirm the difference in protein expression analysis.
The potential role of PR in the formation of AAA requires further
investigation in human and animal models.
The effects mediated by the sex hormone receptors are depen-
dent on their ligands, the sex hormones. Menopause in women
results in lower levels of circulating estrogens, whereas aging men
have increasing levels, due to continued production in the testis and
peripheral aromatization [35,36]. The levels of progesterone are
higher in women compared with men at all ages, while the opposite
is observed for testosterone. Both hormones decrease slightly with
increasing age in men and women [37–39]. A feedback mechanism
could theoretically affect the expression profile of sex hormone
receptors in the aorta, as has been observed for other vascular
disorders [25,40]. Theoretically, the susceptibility to aneurysm for-
mation in men is related to effects mediated by AR. In women, an
aneurysm evolves as the aortic wall loses the protective effect of
being female or due to “male adaptation”.
Women have proportionally smaller aortas than men and there-
fore in AAA development the relative aneurysm enlargement in
women’s AAA exceeds that of men’s at any given diameter [41].
Aortic size index (ASI) is a measurement, which takes the relative
enlargement into account, and has been associated with the risk of
aneurysm rupture in women [23]. In this ASI was higher in women
than in men.
There are limitations to this study such as the limited sample
size, however it is similar to other studies within the field [42,43].
The study illustrates a correlation between the expression levels of
sex hormone receptors and AAA; it is not designed to show cau-
sation. Still, as it is the first of its kind in humans, the data does
provide important information. The lack of appropriate aortic wall
tissue from controls limited the protein expression analysis. The
two splice variants of the ER; ER1 and ERcx, could not be
analysed separately with the used probes and antibodies. These
variants have been shown to have antagonising roles in breast can-
cer but are not widely studied in arteries [44]. Blood samples could
not be obtained from the controls and consequently an analysis
of circulating levels of sex hormones could not be performed. As
in all studies, especially those with a small sample size, both beta
errors (due to small cohorts) and alpha errors (due to multiplicity
of comparisons) should be considered.
In conclusion, the expression profile of sex hormone recep-
tors differs in the aneurysmal aorta compared to unaffected aorta.
A higher expression of AR and a lower expression of ER sug-
gest that sex hormone activity could be associated with aneurysm
development. Further studies are required to determine the clin-
ical implications for patients suffering from sex hormone related
alterations and risk of aneurysm development.
Conflict of interest
The authors declare that they have no conflict of interest.
Contributors
CV was responsible for study design, data collection from
controls, laboratory analysis, statistical analysis, and writing the
manuscript.
PE was responsible for study design, collection of patient sam-
ples, financial support, and critical review of the manuscript.
MK was responsible for laboratory analysis.
ML was responsible for laboratory analysis.
CJ was responsible for data collection from controls, laboratory
analysis, and critical review of the manuscript.
JH was responsible for study design, laboratory analysis, and
critical review of manuscript.
JR was responsible for study design, collection of patient sam-
ples, financial support, and critical review of the manuscript.
RH was responsible for study design, collection of patient and
control aortic wall samples, financial support, critical review of the
manuscript, and had overall responsibility.
Funding
This study was supported by the Swedish Heart-Lung Founda-
tion (Hultgren) and by the regional agreement on medical training
and clinical research (Villard) between Stockholm County Council
and the Karolinska Institutet.
Ethical approval
The study was approved by the local Ethics Commit-
tee (application numbers 2011/1863-3, 2009/4:2, 2009/9-31/4,
2013/615-31/4).
Provenance and peer review
This article has undergone peer review.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.maturitas.2016.
11.005.
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