An Aldose Reductase Inhibitor Prevents the Glucose-Induced Increase in PDGF-β Receptor in Cultured Rat Aortic Smooth Muscle Cells

Abstract

To examine the role of platelet-derived growth factor (PDGF) and the polyol pathway in the growth activity of smooth muscle cells (SMCs), [3H]-thymidine incorporation, [125I]-PDGF-BB binding and expression of PDGF-β receptor protein were measured in rat aortic SMCs cultured with 5.5 or 20 mM glucose with or without anti-PDGF antibody or an aldose reductase inhibitor, epalrestat. SMCs cultured with 20 mM glucose demonstrated an accelerated thymidine incorporation compared with SMCs cultured with 5.5 mM glucose, which 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-β receptors and the overexpression of PDGF-β receptor protein. Epalrestat prevented all these abnormalities. 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-β receptor protein.