Abstract 11668: Transcriptomic Analysis Reveals Sex Differences in Gene Expression Profiling of Stenotic Aortic Valves

Introduction: In aortic stenosis (AS), women present less aortic valve calcification and more aortic valve fibrosis than men for the same hemodynamic severity. However, the specific mediators that drive the fibro-calcific differences between men and women remain unclear. We aim to assess the transcriptome of stenotic aortic valves explanted during aortic valve replacement, according to patient’s sex.

Methods: Transcriptomic profile was obtained from 240 explanted human aortic valves. Among these 240 patients (120 women and 120 men), 62 women were matched with 62 men for age (within 2 years), body mass index (within 2 kg/m ² ), arterial pressure (within 10/5 mmHg), diabetes (exact), hypertension (exact) and AS severity (Table 1). Genes were classified in 6 key processes of AS development: oxidative stress, inflammation, lipid metabolism, fibrosis, apoptosis and calcification following a literature review.

Results: One hundred and ninety (190) genes were differently regulated between men and women: 132 on autosomes and 58 on sexual chromosomes. Among these genes, 106 were over-expressed and 84 were under-expressed in women compared to men (Figure 1). Different genes involved in processes of inflammation, lipid metabolism and calcification were up-regulated both in women and men (women: NET1 , KIF1A, CES1, RCN2; men: FERMT3, APOD, CPAMD8, STC2 ). Genes involved in apoptosis ( SFRP4 ) and fibrosis processes ( TGFβ2 , FRAS1 ) were overexpressed in women.

Conclusions: This study provides evidence that sex may influence aortic valve gene expression through different mechanisms in females and males, favoring pro-fibrotic and pro-apoptotic processes in women.