BACKGROUND
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.
METHODS AND RESULTS
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.
CONCLUSION
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.
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Copyright
© 2021 Published by Elsevier Inc.
