Abstract 84: Group V Secretory Phospholipase A2 Enhances the Progression of Angiotensin II-Induced Abdominal Aortic Aneurysms but Confers Protection Against Angiotensin II-Induced Cardiac Fibrosis in ApoE-Deficient Mice
Objective— Abdominal aortic aneurysms (AAAs) and heart failure are complex life-threatening diseases whose etiology is not completely understood. We recently reported that deficiency of group X secretory phospholipase A2 (GX sPLA2) reduces abdominal aortic aneurysm (AAA) formation in apoE-/- mice infused with angiotensin II. In this study, we investigated whether deficiency of a related enzyme, GV sPLA2, also protects mice from experimental AAA. The impact of GV sPLA2 deficiency on Ang II-induced cardiac fibrosis was also assessed.
Methods and results— ApoE-/- mice and apoE-/- mice lacking GV sPLA2 (GV DKO) were infused with 1000 ng/kg/min Ang II for up to 28 days. Increases in systolic blood pressure, urinary prostanoids, and plasma aldosterone were similar in apoE-/- and GV DKO mice after Ang II infusion. The incidence of aortic rupture in Ang II-infused GV DKO mice (10%) was significantly lower compared to apoE-/- mice (30%). Although the overall incidence of AAA in GV DKO mice (∼81.25%) and apoE-/- mice (100%) was similar, the mean percent increase in maximal luminal diameter of abdominal aortas was significantly smaller in GV DKO mice (68.5±7.7%) compared to apoE-/- mice (92.6±8.3%). Deficiency of GV sPLA2 resulted in increased Ang II-induced cardiac fibrosis that was most pronounced in perivascular regions. Perivascular collagen, visualized by picrosirius red staining, was associated with increased TUNEL staining and increased immunopositivity for macrophage and myofibroblast cells and NOX-2 and NOX-4.
Conclusion— Our findings indicate that GV sPLA2 modulates pathological responses to Ang II, with different outcomes for AAA and cardiac fibrosis. These data have important implications for sPLA2 inhibitors that are currently being developed for clinical use.
- © 2012 by American Heart Association, Inc.