| First Author | Subramanian V | Year | 2010 |
| Journal | Circ Res | Volume | 107 |
| Issue | 8 | Pages | 953-8 |
| PubMed ID | 20798360 | Mgi Jnum | J:178193 |
| Mgi Id | MGI:5297663 | Doi | 10.1161/CIRCRESAHA.110.219089 |
| Citation | Subramanian V, et al. (2010) Pioglitazone-induced reductions in atherosclerosis occur via smooth muscle cell-specific interaction with PPAR{gamma}. Circ Res 107(8):953-8 |
| abstractText | RATIONALE: Peroxisome proliferator-activated receptor (PPAR)gamma agonists attenuate atherosclerosis and abdominal aortic aneurysms (AAAs). PPARgamma, a nuclear receptor, is expressed on many cell types including smooth muscle cells (SMCs). OBJECTIVE: To determine whether a PPARgamma agonist reduces angiotensin II (Ang II)-induced atherosclerosis and AAAs via interaction with SMC-specific PPARgamma. METHODS AND RESULTS: Low-density lipoprotein receptor (LDLR)(-/-) mice with SMC-specific PPARgamma deficiency were developed using PPARgamma floxed (PPARgamma(f/f)) and SM22 Cre(+) mice. PPARgamma(f/f) littermates were generated that did not express Cre (Cre(0/0)) or were hemizygous for Cre (Cre(+/0)). To assess the contribution of SMC-specific PPARgamma in ligand-mediated attenuation of Ang II-induced atherosclerosis and AAAs, both male and female Cre(0/0) and Cre(+/0) mice were fed a fat-enriched diet with or without the PPARgamma agonist pioglitazone (Pio) (20 mg/kg per day) for 5 weeks. After 1 week of feeding modified diets, mice were infused with Ang II (1000 ng/kg per minute) for 4 weeks. SMC-specific PPARgamma deficiency or Pio administration had no effect on plasma cholesterol concentrations. Pio administration attenuated Ang II-increased systolic blood pressure equivalently in both Cre(0/0) and Cre(+/0) groups. SMC-specific PPARgamma deficiency increased atherosclerosis in male mice. Pio administration reduced atherosclerosis in only the Cre(0/0) mice, but not in mice with SMC-specific PPARgamma deficiency. SMC-specific PPARgamma deficiency or Pio administration had no effect on Ang II-induced AAA development. Pio also did not attenuate Ang II-induced monocyte chemoattractant protein-1 production in PPARgamma-deficient SMCs. CONCLUSIONS: Pio attenuates Ang II-induced atherosclerosis via the interaction with SMC-specific PPARgamma, but has no effect on the development of AAAs. |
