Smooth muscle-specific PPARγ deficiency augments angiotensin II-induced atherosclerosis but does not affect abdominal aortic aneurysms in male LDL receptor-deficient mice

Subramanian, Venkateswaran, Bruemmer, Dennis, Golledge, Jonathan, and Daugherty, Alan (2009) Smooth muscle-specific PPARγ deficiency augments angiotensin II-induced atherosclerosis but does not affect abdominal aortic aneurysms in male LDL receptor-deficient mice. In: Arteriosclerosis, Thrombosis, and Vascular Biology (29) P605. E121-E121. From: Arteriosclerosis, Thrombosis, and Vascular Biology Annual Conference 2009, 29 April - 1 May 2009, Washington, DC, USA.

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Abstract

Objective: Chronic infusion of angiotensin II (AngII) augments the development of atherosclerosis and induces abdominal aortic aneurysms (AAAs) in hypercholesterolemic mice. Smooth muscle cells (SMCs) play a pivotal role in the development of these two pathologies. AngII-induced AAA is associated with the downregulation of peroxisome proliferator-activated receptor gamma (PPARgamma). In addition, activation of PPARgamma by ligands attenuates atherosclerosis in male mice. The purpose of the study was to define whether deficiency of SMC-specific PPARgamma influences AngII-induced vascular pathologies.

Methods and Results: Male and female LDL receptor -/- mice were bred with homozygous floxed PPARgamma alleles (PPARgammaf/f). Parental males were also developed that were hemizygous for Cre under the control of the SM22 promoter. Littermates were generated that did not express Cre (Cre0/0, n=20) or were hemizygous for Cre(Cre1/0, n=16) and fed a saturated fat-enriched diet (21% wt/wt milk fat; 0.15% wt/wt cholesterol). Mice were infused with AngII (1,000 ng/kg/min) by osmotic minipump for 4 weeks. AngII increased systolic blood pressure equivalently in both groups. SMC-specific deficiency of PPARgamma had no effect on serum cholesterol concentrations (Cre0/0, 1544±112; Cre1/0, 1548±87 mg/dL) or lipoprotein-cholesterol distributions. AngII infusion led to a similar incidence of AAA formation (84% of male Cre0/0 versus 80% of male Cre1/0 mice). Ex vivo measurement of maximal diameter of abdominal aorta showed a comparable dilation in Cre0/0 and Cre1/0 mice (2.16±0.16 versus 2.17±0.31 mm, P=NS). Male Cre1/0 mice had significantly larger atherosclerotic lesion areas in both arch and thoracic aortic regions by en face measurement compared to male f/fCre0/0 mice (Arch area intimal lesions; Cre0/0 = 4.74±1.13%; Cre1/0 = 10.24±1.67%, Thoracic area intimal lesions; Cre0/0 = 4.12±0.69%; Cre1/0 = 8.99±2.28%, P<0.05, n=12–18 per group). SMC specific PPARgamma deficiency in female LDL receptor -/- mice did not influence either AngII-induced atherosclerosis or AAAs.

Conclusion: SMC specific PPARgamma deficiency augments atherosclerosis but does not contribute to the formation of AAAs induced by AngII in male hyperlipidemic mice.

Item ID: 25044
Item Type: Conference Item (Abstract / Summary)
ISSN: 1524-4636
Date Deposited: 20 Feb 2013 09:20
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1102 Cardiovascular Medicine and Haematology > 110201 Cardiology (incl Cardiovascular Diseases) @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases @ 100%
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