Vascular smooth muscle cell peroxisome proliferator-activated receptor-γ deletion promotes abdominal aortic aneurysms.
Abstract
Peroxisome proliferator-activated receptor-γ (PPARγ) plays an important role in the vasculature; however, the role of PPARγ in abdominal aortic aneurysms (AAA) is not well understood. We hypothesized that PPARγ in smooth muscle cells (SMCs) attenuates the development of AAA. We also investigated PPARγ-mediated signaling pathways that may prevent the development of AAA. We determined whether periaortic application of CaCl(2) renders vascular SMC-selective PPARγ knockout (SMPG KO) mice more susceptible to destruction of normal aortic wall architecture. There is evidence of increased vessel dilatation in the abdominal aorta 6 weeks after 0.25M periaortic CaCl(2) application in SMPG KO mice compared with littermate controls (1.4 ± 0.3 mm [n = 8] vs 1.1 ± 0.2 mm [n = 7]; P = .000119). Results from SMPG KO mice indicate medial layer elastin degradation was greater 6 weeks after abluminal application of CaCl(2) to the abdominal aorta (P < .01). Activated cathepsin S, a potent elastin-degrading enzyme, was increased in SMPG KO mice vs wild-type controls. To further identify a role of PPARγ signaling in reducing the development of AAA, we demonstrated that adenoviral-mediated PPARγ overexpression in cultured rat aortic SMCs decreases (P...Continue Reading
References
Interference with PPAR gamma function in smooth muscle causes vascular dysfunction and hypertension.
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