Abstract

IntroductionAortic valve stenosis (AVS) is the most common valvular disease in the developed world. AVS involves the progressive fibro-calcific 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 nor dietary interventions known to slow AVS progression. Recent studies have begun to suggest oxylipins, a class of bioactive lipid, may be dysregulated in the valves of AVS-patients. MethodologyWe utilized HPLC-MS/MS to conduct a targeted oxylipin analysis on human AV tissue and plasma from a cohort of 110 patients undergoing AV surgery. ResultsWe 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 arachidonic acid-cyclooxygenase (COX) pathway derived prostanoids to be the most associated with AVS severity. Plasma oxylipin levels were measured in a subset of aortic surgery patients and compared to a control group of healthy participants, showing distinct oxylipin profiles between control and disease. ConclusionOur comprehensive analysis of oxylipins in the human AV to date and 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.