Apoptosis induced by 7-ketocholesterol is enhanced in smooth muscle cells derived from OLETF rats.
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-ketocholesterol 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.
Miyashita
Yoh
Y
Center of Diabetes, Endocrine and Metabolism, Sakura Hospital, Toho University School of Medicine, 564 Shimoshizu, Sakura-shi, Chiba 285-8741, Japan. mumon@sf6.so-net.ne.jp
Koide
Nobukiyo
N
Oyama
Tomokazu
T
Itoh
Yoshiaki
Y
Shirai
Kohji
K
D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001161:Arteriosclerosis / Q000209:etiology / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D066298:In Vitro Techniques; D007653:Ketocholesterols / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology*; D051381:Rats; D020334:Rats, Inbred OLETF; D020318:Rats, Long-Evans
D004791:Enzyme Inhibitors; D007653:Ketocholesterols; C003001:7-ketocholesterol