A Transcriptomic Approach to Sex Differences in Calcific Aortic Valve Stenosis in Patients with a Tricuspid Aortic Valve.

Background: Valvular lesions in calcific aortic valve stenosis are sex-specific: female patients reach a similar level of severity as male patients but with less valvular calcification and more valvular fibrosis. We thus aim to assess the transcriptome of stenotic aortic valves according to patients' sex.

Methods: A total of 300 valves were collected, and genomewide gene expression was quantified using a microarray on 240.

Early onset multivalvular disease caused by a missense variant in lamin A/C.

Lamins A/C, coded by LMNA gene, are crucial for nuclear architecture preservation. Pathogenic LMNA variants cause a wide range of inherited diseases called "laminopathies". A subgroup is referred to "progeroid syndromes" characterized by premature aging and other manifestations including cardiac valve abnormalities.

Appraisal of multiple polygenic risk scores to estimate the risk of myocardial infarction and coronary artery lesions.

Background: Polygenic risk scores (PRS) could help to identify individuals with a high genetic risk profile for coronary artery disease (CAD). We aimed to evaluate the association between previously reported PRS and myocardial infarction (MI) as well as the extent and recurrence of coronary artery lesions.

Methods: We validated previously reported CAD-PRS and 6 cardiovascular (CV) risk factors PRS (systolic blood pressure [SBP], type 2 diabetes [T2D], body-mass index [BMI], low-density lipoprotein cholesterol [LDL], triglycerides [TG], and lipoprotein-[a][Lp(a)]) in individuals of European ancestry from two Canadian population-based cohorts, the Canadian Longitudinal Study on Aging (CLSA, N = 24,599) and CARTaGENE (N = 26,806).

Transcriptomic Signatures of Calcific Aortic Valve Stenosis Severity in Human Tricuspid and Bicuspid Aortic Valves.

There is currently no medical therapy for calcific aortic valve stenosis. We aimed to identify transcriptomic signatures of the disease severity. We performed mRNA sequencing from explanted human aortic valves of 500 individuals who underwent aortic valve replacement (n = 440) or a heart transplant (n = 60).

Role of visceral adiposity in the relationship between cardiorespiratory fitness and liver fat in asymptomatic adults.

Excess liver fat (LF) is associated with low cardiorespiratory fitness (CRF), low physical activity, and a deteriorated cardiometabolic health profile including increased visceral adipose tissue (VAT). Whether the association between LF and CRF is mediated by visceral adiposity is unknown. We studied the contribution of VAT to the relationship between CRF and LF in asymptomatic women and men.

RNA interference versus antibody-based PCSK9 inhibition for the prevention of cardiovascular disease: a drug-target Mendelian randomization study.

Aims: RNA interference therapies targeting liver expression of the gene proprotein convertase subtilisin/kexin type 9 (PCSK9) lower LDL-cholesterol (LDL-C) and apolipoprotein B (apoB) levels. As opposed to monoclonal antibodies, which neutralise PCSK9 circulating protein, their effect on atherosclerotic cardiovascular disease (ASCVD) outcomes is unknown. We used genetic variants in the PCSK9 locus influencing PCSK9 function or gene expression in the liver to determine whether antibodies against PCSK9 and RNA interference therapies could have comparable effects on ASCVD.

Aortic valve-specific genes dysregulated in calcific aortic valve stenosis as potential biomarkers and therapeutic targets.

Calcific aortic valve stenosis (CAVS) is the most frequent heart valve disease. Elucidating specific gene expression patterns in the aortic valve could provide new insights for understanding disease pathophysiology. We used local RNA sequencing data from 500 explanted human aortic valves to identify aortic valve-specific genes and compared their expression according to disease status and CAVS severity.

Impact of Lipoprotein(a) on Valvular and Cardiovascular Outcomes in Patients With Calcific Aortic Valve Stenosis.

Background: Lp(a) (lipoprotein(a)) is an independent risk factor for calcific aortic valve stenosis (CAVS). Whether patients with CAVS and high Lp(a) levels are at higher risk of valvular or cardiovascular events is unknown. The aim of this study is to determine whether higher Lp(a) levels are associated with valvular and cardiovascular outcomes in patients with CAVS.

Association of genetically predicted levels of circulating blood lipids with coronary artery disease incidence.

Background And Aims: Estimating the genetic risk of coronary artery disease (CAD) is now possible by aggregating data from genome-wide association studies (GWAS) into polygenic risk scores (PRS). Combining multiple PRS for specific circulating blood lipids could improve risk prediction. Here, we sought to evaluate the performance of PRS derived from CAD and blood lipids GWAS to predict the incidence of CAD.

Visceral adiposity: A major mediator of the relationship between epicardial adiposity and cardiorespiratory fitness in adults.

Background And Aims: Epicardial adiposity has been positively associated with visceral adipose tissue (VAT). Few studies have examined the association between cardiorespiratory fitness (CRF) and epicardial adiposity. Furthermore, whether this relationship was independent of VAT remains unexplored.

Polygenic inheritance and its interplay with smoking history in predicting lung cancer diagnosis: a French-Canadian case-control cohort.

Background: The most near-term clinical application of genome-wide association studies in lung cancer is a polygenic risk score (PRS).

Methods: A case-control dataset was generated consisting of 4002 lung cancer cases from the LORD project and 20,010 ethnically matched controls from CARTaGENE. A genome-wide PRS including >1.

Mendelian randomization reveals interactions of the blood proteome and immunome in mitral valve prolapse.

Background: Mitral valve prolapse (MVP) is a common heart disorder characterized by an excessive production of proteoglycans and extracellular matrix in mitral valve leaflets. Large-scale genome-wide association study (GWAS) underlined that MVP is heritable. The molecular underpinnings of the disease remain largely unknown.

Single-cell and single-nucleus RNA-sequencing from paired normal-adenocarcinoma lung samples provide both common and discordant biological insights.

Whether single-cell RNA-sequencing (scRNA-seq) captures the same biological information as single-nucleus RNA-sequencing (snRNA-seq) remains uncertain and likely to be context-dependent. Herein, a head-to-head comparison was performed in matched normal-adenocarcinoma human lung samples to assess biological insights derived from scRNA-seq versus snRNA-seq and better understand the cellular transition that occurs from normal to tumoral tissue. Here, the transcriptome of 160,621 cells/nuclei was obtained.

Integrative genomic analyses identify candidate causal genes for calcific aortic valve stenosis involving tissue-specific regulation.

There is currently no medical therapy to prevent calcific aortic valve stenosis (CAVS). Multi-omics approaches could lead to the identification of novel molecular targets. Here, we perform a genome-wide association study (GWAS) meta-analysis including 14,819 cases among 941,863 participants of European ancestry.

Plasma IGFBP-2 levels reveal heterogeneity in hepatic fat content in adults with excess visceral adiposity.

Lay Summary: Obesity is frequently accompanied by a fatty liver. However, some individuals with high abdominal fat levels nevertheless have low levels of liver fat. Reasons for such discordant phenotypes are unclear.

Contribution of Lipoprotein(a) to Polygenic Risk Prediction of Coronary Artery Disease: A Prospective UK Biobank Analysis.

Background: Lp(a) (lipoprotein[a]) is a highly atherogenic lipoprotein subfraction that may contribute to polygenic risk of coronary artery disease (CAD), but the extent of this contribution is unknown. Our objective was to estimate the contribution of Lp(a) to polygenic risk of CAD and to evaluate the respective contributions of Lp(a) and a CAD polygenic risk score (PRS) to CAD.

Methods: A total of 372 385 UK Biobank participants of European ancestry free of CAD at baseline were included.

Association between remnant cholesterol and progression of bioprosthetic valve degeneration.

Aims: Remnant cholesterol (RC) seems associated with native aortic stenosis. Bioprosthetic valve degeneration may share similar lipid-mediated pathways with aortic stenosis. We aimed to investigate the association of RC with the progression of bioprosthetic aortic valve degeneration and ensuing clinical outcomes.

Associations of insulin-like growth factor binding protein-2 with metabolic profile and hepatic fat deposition in asymptomatic men and women.

Low circulating levels of insulin-like growth-factor binding protein-2 (IGFBP-2) have been associated with increased adiposity and metabolic alterations such as insulin resistance, dyslipidemia, and nonalcoholic fatty liver disease in individuals with obesity. However, whether IGFBP-2 affects energy metabolism in the early stages of these disorders remains unclear. Herein, we hypothesized that plasma IGFBP-2 concentrations are inversely associated with early liver fat accumulation and alterations in lipid and glucose homeostasis in apparently healthy and asymptomatic men and women.