Upregulation of aldose reductase during foam cell formation as possible link among diabetes, hyperlipidemia, and atherosclerosis.

ABSTRACT:

Objective

Aldose reductase (AR) is the rate-limiting enzyme of the polyol pathway. In diabetes, it is related to microvascular complications. We discovered AR expression in foam cells by gene chip screening and hypothesized that it may be relevant in atherosclerosis.

Methods and results

AR gene expression and activity were found to be increased in human blood monocyte-derived macrophages during foam cell formation induced by oxidized LDL (oxLDL, 100 microg/mL). AR activity as photometrically determined by NADPH consumption was effectively inhibited by the AR inhibitor epalrestat. oxLDL-dependent AR upregulation was further increased under hyperglycemic conditions (30 mmol/L D-glucose) as compared to osmotic control, suggesting a synergistic effect of hyperlipidemia and hyper

SUBMITTER: Gleissner CA 

PROVIDER: S-EPMC2579797 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature