Abstract 20008: Oxolipidomic Analysis of Calcific Stenotic Human Aortic Valves: Correlation of Oxidized Phosphatidylcholine and Lysophosphatidic Acid With Aortic Valve Gradient
Introduction: Aortic valve stenosis (AVS) is the most common heart valvulvar pathology seen in the western world. The pathological mechanism of AVS is still unclear. Recent studies suggest elevated plasma Lp(a) concentrations are associated with increased risk of developing AVS. Lp(a) is the primary transporter of oxidized phosphatidylcholines (OxPCs). It also binds autotaxin, an enzyme that converts lysophosphatidylcholine to lysophosphatidic acid (LPA), which has been postulated to induce valve calcification. The goal of this study was to determine the levels of OxPC and LPA in stenotic human aortic valves and to investigate their correlation to mean transvalvular gradient.
Methods: Human aortic valves were obtained from 14 patients (mean age 71±9 years) at the St. Boniface General Hospital in Winnipeg, Canada undergoing aortic valve replacement surgery. Tissue lipids were extracted from aortic valves and OxPC and LPA content was measured via liquid chromatography coupled to electrospray ionization tandem mass spectrometry using internal standards.
Results: Eighty-four OxPCs were screened for, of which 63 were detected in stenotic valves. Of these, 1-palmitoyl-2-(9-oxo)nonanoyl-sn-glycero-3-phosphocholine (PONPC) was the most abundant with average values representing 0.059±0.026 ng/mg of tissue (p<0.001). 1-palmitoyl-2-azelaoyl-sn-glycero-3-phosphocholine (PAzPC) was the next most abundant (0.019±0.006). OxPCs were then grouped by similar structural characteristics to determine if particular species accumulated in tissue more than others. Fragmented species (0.149±0.046) were significantly greater than the non-fragmented (0.088±0.036) and aldehydes were more abundant than long chain products, followed by acids, isoprostanes and terminal furans (p<0.01). Six LPA species were detected in all valves with 16:0 and 18:1 representing the most dominant forms. Correlation analysis of Total LPA levels with mean transvalvular pressure gradients displayed significant positive associations (r2=0.633, p=0.001). No correlations were observed with any of the OxPCs.
Conclusions: This is the first study to document the accumulation of OxPCs and LPA in human aortic valvular tissue, suggesting a potential target for treatment of AVS.
Author Disclosures: A. Edel: None. A. Stamenkovic: None. R. Chaudhary: None. A. Ravandi: None.
- © 2016 by American Heart Association, Inc.