Smooth muscle-targeted overexpression of peroxisome proliferator-activated receptor gamma disrupts vascular wall structure and function (866.4)

Objective: To explore the role of PPARγ in vascular regulation, smooth muscle VP16-PPARγ-overexpressing mice were subjected to studies of systemic vascular function, biomechanical testing, histological analysis, and molecular characterization. Methods: Mice with a flox-controlled VP16-PPARγ gene were crossed with mice containing a tamoxifen-inducible Cre recombinase driven by a smooth muscle myosin heavy chain promoter. All mice received tamoxifen injections at 6 weeks of age. Experiments were performed at 10-16 weeks of age. Results: Compared to littermate controls, transgenic mice displayed: 1) aortic dilation (by histology, echocardiography, and microCT), 2) increased aortic compliance, 3) reduced blood pressure, 4) 80% reduction in aortic ring contractile forces in response to KCl or phenylephrine, 5) lipid accumulation in the aortic media (Oil Red O staining), and 6) reduction in aortic contractile markers and extra-cellular matrix components with increased expression of adipose markers and selected ...