Conjugated bile acids are elevated in severe calcific aortic valve stenosis

Area of Science:

• Cardiovascular Medicine
• Metabolomics
• Biochemistry

Background:

• Calcific aortic valve stenosis (CAVS) is a prevalent condition in aging populations, contributing to significant morbidity and mortality.
• Recent research indicates bile acids play a role in various disease processes, with disrupted bile acid pathways observed in CAVS patient valves.
• Understanding valvular bile acid changes is crucial for elucidating CAVS pathophysiology.

Purpose of the Study:

• To investigate the alterations in human valvular bile acid composition in relation to the severity of calcific aortic stenosis (CAVS).
• To identify specific bile acids associated with different stages of aortic stenosis (AS) and valve calcification.

Main Methods:

• Analysis of 100 human aortic valves (AVs) from patients undergoing AV replacement surgery.
• Quantification of bile acids using ultrahigh-performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS).
• Statistical analysis and K-means clustering to correlate bile acid profiles with AS severity and calcification scores.

Main Results:

• Distinct valvular bile acid profiles were observed between mild and moderate/severe AS groups.
• Five bile acids, including norcholic, nordeoxycholic, glycodeoxycholic, glycocholic, and taurodeoxycholic acid, were significantly elevated in moderate and severe AS.
• Conjugated primary and secondary bile acids were notably increased in stenotic valves compared to mild AS, indicating a link to disease progression.

Conclusions:

• Valvular bile acid composition significantly differs based on the severity of calcific aortic stenosis.
• Elevated conjugated bile acids in stenotic valves suggest a potential role in CAVS pathophysiology.
• Findings point towards a possible connection between liver-gut microbiome function, bile acid metabolism, and the development of valvular stenosis.