Valvular Prostaglandins Are Elevated in Severe Human Aortic Valve Stenosis.

Abstract

Aortic valve stenosis (AVS) is the most common valvular disease in the developed world. AVS involves the progressive fibrocalcific remodeling of the aortic valve (AV), which impairs function and can ultimately lead to heart failure. Due to gaps in our understanding of the underlying mechanisms of AVS, there are no pharmacological treatments or dietary interventions known to slow AVS progression. Recent studies have begun to suggest oxylipins-a class of bioactive lipids-may be dysregulated in the valves of patients with AVS. We utilized high-performance liquid chromatography-tandem mass spectrometry to conduct a targeted oxylipin analysis on human AV tissue and plasma from a cohort of 110 patients undergoing AV surgery. We identified 36 oxylipins in human AV tissue with all showing significant increase in patients with severe AVS. A multivariate model including patient characteristics and valvular oxylipins identified the arachidonic acid-COX (cyclooxygenase) pathway-derived prostanoids to be the most associated with AVS severity. Plasma oxylipin levels were measured in a subset of AV surgery patients and compared with a control group of healthy participants, showing distinct oxylipin profiles between control and disease. Our comprehensive analysis of oxylipins in the human AV identified the inflammatory and osteogenic regulating prostanoids to be positively correlated with AVS severity. This elucidation of prostanoid dysregulation warrants further research into COX inhibition to mitigate AVS.