Group V secreted phospholipase A₂ plays a protective role against aortic dissection

Aortic dissection is a life-threatening aortopathy involving separation of the aortic wall, whose underlying mechanisms are still incompletely understood. Epidemiological evidence suggests that unsaturated fatty acids improve cardiovascular health. Here, using quantitative RT-PCR, histological analyses, magnetic cell sorting and flow cytometry assays, and MS-based lipidomics, we show that the activity of a lipid-metabolizing enzyme, secreted phospholipase A₂ group V (sPLA₂-V), protects against aortic dissection by endogenously mobilizing vasoprotective lipids. Global and endothelial cell-specific sPLA₂-V-deficient mice frequently developed aortic dissection shortly after infusion of angiotensin II (AT-II). We observed that in the AT-II-treated aorta, endothelial sPLA₂-V mobilized oleic and linoleic acids, which attenuated endoplasmic reticulum stress, increased the expression of lysyl oxidase, and thereby stabilized the extracellular matrix in the aorta. Of note, dietary supplementation with oleic or linoleic acid reversed the increased susceptibility of sPLA₂-V-deficient mice to aortic dissection. These findings reveal an unexplored functional link between sPLA₂-driven phospholipid metabolism and aortic stability, possibly contributing to the development of improved diagnostic and/or therapeutic strategies for preventing aortic dissection.