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Smooth muscle‐targeted overexpression of peroxisome proliferator‐activated receptor gamma disrupts vascular wall structure and function (866.4)
Author(s) -
Sutliff Roy,
Kleinhenz Jennifer,
Murphy Tamara,
PokuttaPaskaleva Anastassia,
Gleason Rudolph,
Lyle Alicia,
Taylor W.,
Yang Qinglin,
Hart C.
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.866.4
Subject(s) - vascular smooth muscle , endocrinology , peroxisome proliferator activated receptor , receptor , medicine , adipose tissue , chemistry , biology , smooth muscle
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 mitochondrial proteins (by qPCR).Conclusion: These results demonstrate that targeted overexpression of activated PPARγ in smooth muscle disrupts vascular wall structure and function in part by driving medial smooth muscle towards an adipocyte phenotype. Grant Funding Source : Supported by grants from NIH (R01 HL102167) and VA (Merit Review Award 1I01BX001910)