VALVULAR BILE ACIDS CORRELATE WITH THE DEGREE OF STENOSIS IN PATIENTS WITH CALCIFIC AORTIC VALVE STENOSIS

Abstract

<h3>BACKGROUND</h3> Calcific aortic valve stenosis (CAVS) is the most common valvular pathology seen in the Western world. The pathological mechanism of CAVS is still unclear and currently no medical therapy to prevent or reduce the progression of CAVS exists. Our recent metabolomics analysis of human aortic valve tissue identified bile acid biosynthesis as a potential mitigator of valvular stenosis. In this study, we sought to build on these preliminary results by conducting a targeted bile acid analysis of human calcific aortic valve tissues. <h3>METHODS AND RESULTS</h3> Human aortic tissue valves from 102 patients undergoing aortic valve replacement surgery were collected from St. Boniface Hospital. Bile acid profiling (80 bile acids) of valvular tissues along with 19 plasma samples was carried out by liquid chromatography coupled to electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS). Three bile acids namely nordeoxycholic acid, norcholic acid and glycodeoxycholic acids were significantly altered (p < 0.05) between different degrees of CAVS severity based on the mean pressure gradient. Similarly, nordeoxycholic acid and norcholic acid, as well as 4 other bile acids namely 3β,7α-diOH-5-cholestenoic acid, 3β-OH-5-cholestenoic acid, glycolithocholic acid, and glycoallocholic acid were significantly altered (p < 0.05) across CAVS severity based on the valvular calcification score. In addition, the levels of these bile acids in valvular tissues correlate significantly with plasma levels. <h3>CONCLUSION</h3> In this report, we present a novel mechanistic pathway correlation for bile acids in the pathogenies of CAVS. Our goal is to validate these findings in a large cohort of patients with CAVS. Given that bile acid modulating therapies are already used in clinical practice, the bile acid pathway may be a potential therapeutic target to prevent or delay the progression of CAVS.