Peroxisome Proliferator-Activated Receptor-γ1 Gene Therapy Attenuates Atherosclerosis and Stabilizes Plaques in Apolipoprotein E-Deficient Mice

Peroxisome proliferator-activated receptor-γ1 (PPARγ1) is an important transcription factor involved in atherosclerosis progression. Thus, PPARγ1 appears to be an interesting gene therapeutic target to favorably affect atherosclerosis development. The present study was carried out to test the hypothesis that PPARγ1 gene therapy may attenuate and stabilize atherosclerotic plaques in apolipoprotein E-knockout mice. The recombinant adenovirus carrying mouse PPARγ1 cDNA (AdPPARγ1) was constructed and AdPPARγ1 (5 × 108 PFU) or AdGFP (5 × 108 PFU), diluted to a total volume of 200 μl, was injected into the tail vein of mice (40 weeks of age and fed a high-fat diet) in two intervention groups (n = 20 each). Mice (n = 20) injected with phosphate-buffered saline (PBS) served as vehicle controls. The results showed that 4-week treatment with AdPPARγ1 attenuated atherosclerotic lesions, although the overall mRNA levels of CD36 were increased in the AdPPARγ1 group. Moreover, PPARγ1 gene overexpression stabilized athe...