Manidipine affects rPDGF-BB-induced gene transcription of low-density lipoprotein receptors and 3-hydroxy-3-methylglutaryl coenzyme A reductase in human mesangial cells.

The effects of manidipine, a newly developed Ca2+ channel blocker, on recombinant platelet-derived growth factor BB (rPDGF-BB)-induced transcription of the low-density lipoprotein receptor and the 3-hydroxy-3-methylglutaryl coenzyme A reductase genes in human mesangial cells are reported. The transcription of the rPDGF-BB-induced gene of the low-density lipoprotein receptor was enhanced and maintained over a longer period, whereas the transcription of the 3-hydroxy-3-methylglutaryl reductase gene was blocked by manidipine at nanomolar concentrations. The results suggest that aside from the ability to block manidipine's potential-operated Ca2+ channels, manidipine also affects gene transcription of relevant proteins involved in the regulation of cholesterol metabolism at concentrations close to those efficacious for clinical therapies. This may further explain the antiinflammatory and organ-protective activities of the compound.