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Atherosclerosis is a lipid-driven inflammatory disease presumably initiated by endothelial activation. Low vascular shear stress is known for its ability to activate endothelial cells. Differential DNA methylation (DNAm) is a relatively unexplored player in atherosclerotic disease development and endothelial dysfunction. Previous studies showed that the expression of 11 genes was associated with differential DNAm due to low shear stress in murine endothelial cells. We hypothesized a causal relationship between DNAm of shear stress associated genes in human carotid plaque and increased risk of cardiovascular disease.
Using Mendelian randomisation (MR) analysis, we explored the potential causal role of DNAm of shear stress associated genes on cardiovascular disease risk. We used data from the Athero-Expression Biobank Study for the discovery of methylation quantitative trait loci (mQTLs) in 442 advanced carotid plaques. Next, we performed MR analysis using these mQTLs and publicly available GWAS summary statistics of coronary artery disease (CAD) and ischemic stroke (IS).
We discovered 9 mQTLs in plaque in the promoters of shear stress associated genes. We found no significant effect of shear stress gene promoter methylation and increased risk of CAD and IS.
Differential methylation of shear stress associated genes in advanced atherosclerotic plaques in unlikely to increase cardiovascular risk in human.
Differential methylation of shear stress associated genes in advanced atherosclerotic plaques in unlikely to increase cardiovascular risk in human.
Serum calcium abnormality is associated with adverse cardiovascular outcomes, but the effects of serum calcium level on stroke outcomes remain unknown. We aimed to assess the relationship between serum calcium level and 1-year outcomes in patients with acute ischemic stroke and transient ischemic attack.
We included 9375 stroke patients from the China National Stroke Registry III for analysis. Participants were divided into 4 groups according to albumin corrected-calcium quartiles. Composite end point comprised recurrent stroke, myocardial infarction, other ischemic vascular events, and all-cause mortality. Multivariable Cox or logistic regression was used to evaluate the independent association of albumin corrected-calcium with all-cause mortality, recurrent stroke, composite end point, and poor functional outcome (modified Rankin Scale score ≥3).
Compared with the lowest calcium quartile (<2.16mmol/L), the adjusted hazard ratio (95% CI) of the top quartile (≥2.31mmol/L) was 1.56 (1.11-2.18) for all-cause mortality, 1.06 (0.87-1.28) for recurrent stroke and 1.08 (0.90-1.01) for composite end point, and the adjusted odds ratio for poor functional outcome was 1.18 (0.96-1.44). The addition of serum calcium to conventional risk factors improved risk prediction of all-cause mortality, leading to a small but significant increase in C-statistics and reclassification with non-significant integrated discrimination improvement (C-statistics, p= 0.02; net reclassification index 11.8%, p= 0.038; integrated discrimination improvement 0.08%, p= 0.42).
High serum calcium levels at baseline were associated with all-cause mortality at 1-year after ischemic stroke, suggesting that serum calcium may be a potential prognostic biomarker and therapeutic target for ischemic stroke.
High serum calcium levels at baseline were associated with all-cause mortality at 1-year after ischemic stroke, suggesting that serum calcium may be a potential prognostic biomarker and therapeutic target for ischemic stroke.
French Guidelines on Fetal Growth Restriction (FGR) were published in December 2013. It seemed interesting to us to carry out an inventory on the management of FGR in teaching hospitals and tertiary referral centers MATERIAL AND METHODS We carried out a retrospective survey on the academic year 2020/2021. All teaching hospitals and level III maternity in mainland France were contacted (67). The questionnaire focused on the growth curves used, the etiological assessment carried out, the rate and modalities of antenatal surveillance as well as the criteria indicating a birth.
The response rate was 76%. The CFEF curves are used for screening in 78.4% of centers and in the event of FGR in 39.2% of them. The etiological assessment includes a referent ultrasound in 62.7% of cases and amniocentesis is offered in 74.5% of hospitals in case of severe and early FGR. All centers use umbilical Doppler for FGR. The fetal heart rate is monitored between once a week to three times a day in the event of cerebro-placental redistribution. In case of reverse flow, birth is induced from 28 weeks on for some teams while others continue the pregnancy until 39 weeks. In case of cessation of fetal growth, the expected terms of birth are between 28 and 38 weeks.
There is great heterogeneity in the management of FGR, particularly in terms of antenatal surveillance and the term of birth envisaged.
There is great heterogeneity in the management of FGR, particularly in terms of antenatal surveillance and the term of birth envisaged.The molecular understanding of the pathophysiological changes elicited by diabetes in platelets may help in further elucidating the involvement of this pseudo-cell in the increased risk of developing cardiovascular disease and thrombosis in diabetic subjects. We aimed to investigate the differential characteristics of platelets from diabetic patients and nondiabetic controls to unveil the molecular mechanisms behind the increased platelet reactivity in diabetes. We compared platelets from diabetic and control subjects by 2 dimensional-electrophoresis followed by mass spectrometry. Changes in selected differential proteins were validated by immunoprecipitation assays and western blot. Platelet aggregation was measured by light transmittance aggregometry induced by collagen and ADP, and dynamic coagulation analysis of whole blood was measured by thromboelastometry. learn more We observed significant differences in proteins related to platelet aggregation, cell migration, and cell homeostasis. Subjects with diabetes showed higher platelet aggregation and thrombogenicity and higher contents of the stress-related protein complex HSPA8/Hsp90/CSK2α than nondiabetic subjects.
Website: https://www.selleckchem.com/products/gs-4224.html
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