title: Apoptosis induced by 7-ketocholesterol is enhanced in smooth muscle cells derived from OLETF rats.
abstract: 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.
authors.affiliation: 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
authors.forename: Yoh
authors.initials: Y
authors.lastname: Miyashita
authors.forename: Nobukiyo
authors.initials: N
authors.lastname: Koide
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Oyama
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Itoh
authors.forename: Kohji
authors.initials: K
authors.lastname: Shirai
mesh_terms: 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
chemical_list: D004791:Enzyme Inhibitors; D007653:Ketocholesterols; C003001:7-ketocholesterol