Group v secretory phospholipase A 2 Enhances the progression of angiotensin IIInduced abdominal aortic aneurysms but confers protection against angiotensin iiinduced cardiac fibrosis in ApoE-deficient mice

Boris B. Boyanovsky, William Bailey, Lauren Dixon, Preetha Shridas, Nancy R. Webb

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Abdominal aortic aneurysms (AAAs) and heart failure are complex life-threatening diseases whose etiology is not completely understood. In this study, we investigated whether deficiency of group V secretory phospholipase A 2 (GV sPLA 2) protects from experimental AAA. The impact of GV sPLA 2 deficiency on angiotensin (Ang) IIinduced cardiac fibrosis was also investigated. Apolipoprotein E (apoE) -/- mice and apoE -/- mice lacking GV sPLA 2 (GV DKO) were infused with 1000 ng/kg per minute Ang II for up to 28 days. Increases in systolic blood pressure, plasma aldosterone level, and urinary and heart prostanoids were similar in apoE -/- and GV DKO mice after Ang II infusion. The incidence of aortic rupture in Ang IIinfused GV DKO mice (10%) was significantly reduced compared with apoE -/- mice (29.4%). Although the incidence of AAA in GV DKO mice (81.3%) and apoE -/- mice (100%) was similar, the mean percentage increase in maximal luminal diameter of abdominal aortas was significantly smaller in GV DKO mice (68.5% ± 7.7%) compared with apoE -/- mice (92.6% ± 8.3%). Deficiency of GV sPLA 2 resulted in increased Ang IIinduced 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 macrophages and myofibroblasts and nicotinamide adenine dinucleotide phosphate oxidase (NOX)-2 and NOX-4, respectively. Our findings indicate that GV sPLA 2 modulates pathological responses to Ang II, with different outcomes for AAA and cardiac fibrosis.

Original languageEnglish
Pages (from-to)1088-1098
Number of pages11
JournalAmerican Journal of Pathology
Volume181
Issue number3
DOIs
StatePublished - Sep 2012

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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