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Altered vascular function in endothelial‐specific peroxisome proliferator‐activated receptor gamma (PPARγ) null mice
Author(s) -
Bland Jennifer M.,
Kleinhenz Dean J.,
Hansen Jason M.,
Ritzenthaler Jeff D.,
Sutliff Roy L.,
Hart C. Michael
Publication year - 2008
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.22.1_supplement.964.29
Subject(s) - chemistry , peroxisome proliferator activated receptor , nitric oxide , oxidative stress , reactive oxygen species , receptor , endothelial dysfunction , glutathione , medicine , endocrinology , microbiology and biotechnology , biochemistry , biology , enzyme
Objective: To explore the role of PPARγ in vascular regulation, endothelial PPARγ‐deficient mice (ePPARγ−/−) were subjected to studies of systemic vascular function. Methods: Mice with a floxed PPARγ gene were bred with mice expressing Cre recombinase driven by the endothelial promoter, Tie‐2. Subsequent ePPARγ−/− mice were selected by genotyping. Blood pressure of littermate control (Control) and ePPARγ−/− mice was monitored with telemetry. Aortic ring relaxation responses were determined in a muscle bath. Aortic nitric oxide (NO) production was measured with electron spin resonance spectroscopy and Fe(DETC)2. Aortic NF‐kB nuclear binding was detected by EMSA. Plasma levels of cysteine and cystine (Cys:CySS) were determined by HPLC, and derivatives of reactive oxygen metabolites (dROMs) by ELISA. Results: Compared to Controls, ePPARγ−/− animals did not demonstrate significant increases in mean arterial pressure. However, ePPARγ−/− mice displayed: 1) significant reductions in endothelium‐dependent vasorelaxation and aortic NO production, 2) increased aortic NF‐kB nuclear binding, and 3) increased vascular oxidative stress manifested as oxidation of the Cys:CySS redox couple and increased dROMs. Conclusion: Vascular endothelial PPARγ plays an important role in maintenance of redox balance in the vasculature. Supported by grants from the NIH, VA Research Service, and Takeda Pharmaceuticals.