Impaired expression of PPARγ protein contributes to the exaggerated growth of vascular smooth muscle cells in spontaneously hypertensive rats

Peroxisome proliferator-activated receptor γ (PPARγ), a member of the nuclear receptor family, has been implicated in the regulation of vascular smooth muscle cell (VSMC) growth; however, the underlying mechanisms are still not fully understood. We hypothesized that PPARγ functional deficiency may contribute to the enhanced proliferation of VSMC associated with hypertension in spontaneously hypertensive rats (SHR). We observed that PPARγ mRNA level in SHR VSMC was 3∼4 fold higher than that from Wistar–Kyoto rats (WKY), but the protein expression levels of PPARγ are significantly lower in SHR than WKY VSMC, suggesting an impaired control of PPARγ protein expression in SHR VSMC. The deficiency of PPARγ protein expression in SHR VSMC was demonstrated by PPARγ reporter gene assays. Furthermore, the exaggerated growth of SHR VSMC was markedly attenuated by adenoviral PPARγ overexpression. Taken together, our results provided the first direct evidence that impaired expression of PPARγ protein contributes to the exaggerated growth of SHR VSMC.