Increased atherogenesis in Otsuka Long-Evans Tokushima fatty rats before the onset of diabetes mellitus: association with overexpression of PDGF beta-receptors in aortic smooth muscle cells

The mechanism of diabetic macroangiopathy was studied from the view point o f phenotypic change of arterial smooth muscle cells (SMC). Otsuka Long-Evan s Tokushima fatty (OLETF) rat, an animal model of non-insulin dependent dia betes mellitus (NIDDM), develops spontaneous persistent hyperglycemia after the age of 18 weeks. Medial SMC in OLETF rats expressed more platelet-deri ved growth factor (PDGF) beta-receptor and fibronectin at the protein level than those from control, Long-Evans Tokushima Otsuka (LETO) rats, not only after but also before the onset of diabetes mellitus. Cultured SMC from OL ETF rats more strongly responded specifically to the mitogenic stimuli of P DGF-AB and PDGF-BB and also expressed PDGF beta-receptor more intensely com pared with those from LETO rats. PDGF is known to be the main contributor t o the intimal thickening induced by balloon catheter injury, which is one o f several forms of arterial injuries. Intimal thickening of carotid arterie s in OLETF rats after balloon catheter injury increased compared with that in LETO rats before the onset of diabetes mellitus. In in vitro culture sys tem, fibronectin synthesis was stimulated by transforming growth factor-bet a 1(TGF-beta 1) in SMC From OLETF rats, but not in those from LETO rats, su ggesting that SMC from OLETF rats respond to TGF-beta 1. These results indi cate that overexpression of PDGF beta-receptor and fibronectin in medial SM C plays an important role in the accelerated intimal thickening before the onset of diabetes mellitus in OLETF rats. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.