An aldose reductase inhibitor prevents the glucose-induced increase in PDGF-beta receptor in cultured rat aortic smooth muscle cells

To examine the role of platelet-derived growth factor (PDGF) and the polyol pathway in the growth activity of smooth muscle cells (SMCs), [H-3]-thymid ine incorporation, [I-125]-PDGF-BB binding and expression of PDGF-beta rece ptor protein were measured in rat aortic SMCs cultured with 5.5 or 20 mM gl ucose with or without anti-PDGF antibody or an aldose reductase inhibitor, epalrestat. SMCs cultured with 20 mM glucose demonstrated an accelerated th ymidine incorporation compared with SMCs cultured with 5.5 mM glucose, whic h was prevented by anti-PDGF antibody. This acceleration of growth activity by 20 mM: glucose was accompanied by an increase in PDGF-BB binding, which was due to the increased number of PDGF-beta receptors and the overexpress ion of PDGF-beta receptor protein. Epalrestat prevented all these abnormali ties. These observations suggest that polyol pathway hyperactivity plays an important role in the proliferation of SMCs which may be mediated through the accelerated expression of PDGF-beta receptor protein. (C) 1999 Academic Press.