Apoptosis Induced by 7-Ketocholesterol is Enhanced in Smooth Muscle Cells Derived from OLETF Rats

  • Miyashita Yoh
    Center of Diabetes, Endocrine and Metabolism, Sakura Hospital, Toho University School of Medicine, Chiba, Japan.
  • Koide Nobukiyo
    Center of Diabetes, Endocrine and Metabolism, Sakura Hospital, Toho University School of Medicine, Chiba, Japan.
  • Oyama Tomokazu
    Center of Diabetes, Endocrine and Metabolism, Sakura Hospital, Toho University School of Medicine, Chiba, Japan.
  • Itoh Yoshiaki
    Center of Diabetes, Endocrine and Metabolism, Sakura Hospital, Toho University School of Medicine, Chiba, Japan.
  • Shirai Kohji
    Center of Diabetes, Endocrine and Metabolism, Sakura Hospital, Toho University School of Medicine, Chiba, Japan.

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To clarify whether an increased proliferative potential of vascular smooth muscle cells (SMC) under diabetic conditions augments the susceptibility of the cells to 7-ketocholesterol-induced apoptosis, we investigated the difference in sensitivity to 7-ketocholesterol between SMC obtained from diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats and the control Long-Evans Tokushima Otsuka (LETO) rats. The outgrowth rate from aortic wall explants and cell proliferation were higher in SMC derived from OLETF rats (OLETF-derived SMC) compared to those from LETO rats (LETO-derived SMC). When 7-ketocholesterol was added to SMC, the amount of fragmented DNA increased significantly in OLETF-derived compared to LETO-derived SMC. The amount of fragmented DNA induced by 7-ketocholeaterol decreased significantly in both OLETF- and LETO-derived SMC when they were incubated without fetal bovine serum. By adding PDGF-BB to LETO-derived SMC, the amount of fragmented DNA induced by 7-ketocholesterol increased significantly. These results suggest that apoptosis of SMC induced by 7-ketocholesterol may be accelerated when SMC acquire a high proliferative potential by prolonged exposure to diabetic condition.

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