(VP075) MODULATION OF GENE EXPRESSION IN STENOTIC AORTIC VALVES OF WOMEN

Background: Valvular lesions in aortic stenosis (AS) are different according to the patient’s sex: women reach similar hemodynamic severity of AS with lower aortic valve calcification and higher valvular fibrosis compared to men. In this context, we aim to assess the transcriptomic profile of stenotic valves explanted during aortic valve replacement according to the patient’s sex.

METHODS AND RESULTS: Transcriptomic profiling from 240 aortic valves was performed. Among these 240 patients (120 women and 120 men), 62 women were matched 1:1 with 62 men for age (within 2 years), body mass index (within 2 kg/m2), arterial pressure (within 10/5 mmHg), diabetes (exact), hypertension (exact) and AS severity (Table 1). Genes were classified in 6 key processes know to be responsible for AS development: oxidative stress, inflammation, lipid metabolism, fibrosis, apoptosis, and calcification following a literature review.
One hundred and ninety (190) genes were regulated differently 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 associated with apoptosis (SFRP4) and fibrosis processes (TGFB2 and FRAS1) were overexpressed in women.

Conclusion: 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.