INCREASED PROLIFERATION OF EXPLANTED VASCULAR SMOOTH-MUSCLE CELLS - AMARKER PRESAGING ATHEROGENESIS

The JCR:LA-cp homozygous cp/cp corpulent rat is genetically predispose d to develop atherosclerosis evident after 9 and 18 months of age in m ales and females and to manifest metabolic derangements resembling tho se seen in type II diabetes in humans (hyperinsulinemia, insulin resis tance, hyperglycemia and hypertriglyceridemia). The present study was undertaken to determine whether vascular smooth muscle cells (SMCs) ex planted from vessels destined to become atherosclerotic later in life exhibit intrinsic properties ex vivo that presage atherogenesis to pro vide a means for evaluating promptly intervention designed to modify i t. SMCs were cultured from aortic explants of JCR:LA-cp corpulent (cp/ cp) and lean control (+/+) rats of 4, 5, 6, and 9 months of age. Compa red with SMCs from controls, SMCs from cp/cp rats exhibited increased proliferation, higher saturation density, increased augmentation of pr oliferation in response to selected mitogens and greater adherence to extracellular matrix proteins. The increased proliferative activity ex vivo anteceded by several months the development of atherosclerotic l esions in vivo Thus, it is a promising marker in assessments of the ef ficacy of interventions designed to retard or prevent atherosclerosis. (C) 1997 Elsevier Science Ireland Ltd.