DOI: 10.1161/circ.148.suppl_1.11668 ISSN: 0009-7322

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

Emma Le Nezet, Martine Voisine, Rose Tam, Zhonglin LI, Nathalie Gaudreault, Nancy Cote, Sebastien Theriault, Yohan Bosse, Marie-Annick A Clavel
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

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.

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