Abstract 13832: Lysophosphatidylcholine Derived From Lp-PLA2 Promotes the Mineralization of the Aortic Valve
Objectives: In this work we aimed to document the role of Lp-PLA2 in calcific aortic valve disease (CAVD).
Background: CAVD is a chronic disorder, which is characterized by pathological mineralization and remodelling. Studies have underlined that human AS tissues are infiltrated by lipids and that inflammation may play a role into the pathobiology. We hypothesized that lipoprotein-associated phospholipase A2 (Lp-PLA2/PLA2G7) is expressed in CAVD and plays a role in promoting the mineralization of valve interstitial cells (VICs).
Methods: We have documented the expression of phospholipase A2 family of genes in aortic valves in a genome-wide gene expression experiment. The levels of mRNA and protein expression were confirmed in aortic valves explanted from 60 patients by q-PCR and immunohistochemistry. The effect of lysophosphatidylcholine (LPC), the end-product of Lp-PLA2 activity, was documented in the mineralization of VIC cultures.
Results: Transcriptomic analyses of CAVD and control non-mineralized aortic valves demonstrated that Lp-PLA2 was increased by 4.2-fold in mineralized aortic valves. Higher expression of Lp-PLA2 in stenotic aortic valves was confirmed by q-PCR, immunohistochemistry, and enzymatic Lp-PLA2 activity. The number of Lp-PLA2 transcripts correlated with several indices of tissue remodelling. In vitro, LPC increased the mRNA expression of ectonucleotidase enzymes and bone-related peptides. We then showed that LPC-induced mineralization involved the ectonucleotidase enzyme as well as apoptosis through a PKA-dependent pathway.
Conclusions: These results showed that Lp-PLA2 is highly expressed in CAVD and promotes the mineralization of VICs. Further work is necessary to explore whether Lp-PLA2 is as novel therapeutic target for CAVD.
- © 2013 by American Heart Association, Inc.