Figure 7.

Exogenous supply of OA and LA protects against aortic dissection in Pla2g5^−/− mice. A, representative photographs of thoracic aortas in Pla2g5^+/+ and Pla2g5^−/− mice fed a normal chow diet, a Western diet, an olive oil–rich diet, or a corn oil–rich diet after 7 days of AT-II infusion. Arrows, aortic dissection with intramural hematoma. Scale bars, 1 mm. B, incidence of thoracic aortic dissection or rupture in Pla2g5^+/+ and Pla2g5^−/− mice fed a normal chow diet (n = 25), a Western diet (n = 8–11), an olive oil–rich diet (n = 8), or a corn oil–rich diet (n = 8) within 7 days of AT-II infusion. C and D, mRNA expression of Lox (C) and Gata3 (D) in the aortas of Pla2g5^+/+ and Pla2g5^−/− mice after AT-II infusion for 48 h fed normal chow, an olive oil–rich diet, or a corn oil–rich diet (n = 6–8). *, p < 0.05; **, p < 0.01; ns, not significant by two-way ANOVA followed by Tukey's multiple-comparison test. E, Pla2g5 expression in the aorta of Pla2g5^+/+ mice fed a normal chow or an olive oil–rich diet (n = 3). **, p < 0.01 by unpaired t test. Data are presented as mean ± S.E. (error bars) of the indicated number (n) of biological replicates. F, schematic diagram of the roles of endothelial sPLA₂-V in aortic stabilization. sPLA₂-V is a major sPLA₂ isoform expressed in aortic ECs and is largely retained on the luminal surface of the aortic endothelium likely through binding to heparan sulfate proteoglycans. Endothelial sPLA₂-V acts on membrane phospholipids of AT-II–activated ECs to mobilize OA and LA, which in turn promote AT-II–induced up-regulation of LOX that facilitates ECM cross-linking, thereby stabilizing the aortic wall. Impairment of this sPLA₂-V–driven lipid pathway leads to increased susceptibility to aortic dissection.