Peroxisome proliferator-activated receptor (PPAR)γ agonists attenuate atherosclerosis and abdominal aortic aneurysms (AAAs). PPARγ, a nuclear receptor, is expressed on many cell types including smooth muscle cells (SMCs).

To determine whether a PPARγ agonist reduces angiotensin II (Ang II)–induced atherosclerosis and AAAs via interaction with SMC-specific PPARγ.

Low-density lipoprotein receptor (LDLR)^−/− mice with SMC-specific PPARγ deficiency were developed using PPARγ floxed (PPARγ^f/f) and SM22 Cre⁺ mice. PPARγ^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 PPARγ 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 PPARγ 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 PPARγ 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 PPARγ deficiency increased atherosclerosis in male mice. Pio administration reduced atherosclerosis in only the Cre^0/0 mice, but not in mice with SMC-specific PPARγ deficiency. SMC-specific PPARγ 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 PPARγ-deficient SMCs.

Pio attenuates Ang II–induced atherosclerosis via the interaction with SMC-specific PPARγ, but has no effect on the development of AAAs.