Aldose reductase inhibitor prevents hyperproliferation and hypertrophy of cultured rat vascular smooth muscle cells induced by high glucose.
Vascular remodeling is a key process in the pathophysiology of atherosclerosis. Recent evidence suggests that high glucose levels may function as a vascular smooth muscle growth and proliferation-promoting substance. To explore the role of the polyol pathway in this process, we examined the effect of an aldose reductase inhibitor (ARI), epalrestat, on the growth characteristics of cultured rat vascular smooth muscle cells (VSMCs). Epalrestat (10 nmol/L, 1 mumol/L) significantly suppressed the high glucose-induced proliferative effect as measured by [3H]thymidine incorporation by 67% and 82% in cell number, suggesting ARI as an antimitogenic factor. In VSMCs, epalrestat (10 nmol/L, 1 mumol/L) significantly suppressed the high glucose-induced incorporation of [3H]leucine by 45% and 58% with the concomitant reduction of the cell size estimated by flowcytometry. Epalrestat (1 mumol/L) also suppressed high glucose-induced intracellular NADH/NAD+ increase and membrane-bound protein kinase C activation. These results indicate that this ARI possesses an antiproliferative and antihypertrophic action on VSMCs induced by high glucose possibly through protein kinase C suppression.
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D005434:Flow Cytometry; D005947:Glucose / Q000494:pharmacology*; D006984:Hypertrophy; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology*; D011506:Proteins / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012236:Rhodanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D053778:Thiazolidines
D011506:Proteins; D053778:Thiazolidines; C038131:epalrestat; D012236:Rhodanine; D004247:DNA; D000449:Aldehyde Reductase; D005947:Glucose