Enalapril stimulates collagen biosynthesis through prolidase-dependent mechanism in cultured fibroblasts
Abstract
The mechanism of a lower incidence of dermatological manifestations in patients treated with enalapril compared to patients treated with other ACE-inhibitors, e.g., captopril, is not known. The finding that prolidase plays an important role in collagen biosynthesis and that some angiotensin-converting enzyme inhibitors affect prolidase activity led us to evaluate its effect on collagen biosynthesis in cultured human skin fibroblasts. Since insulin-like growth factor (IGF-I) and transforming growth factor beta 1 (TGF-β1) are the most potent stimulators of both collagen biosynthesis and prolidase activity, and prolidase is regulated by β1 integrin signaling, the effect of enalapril and enalaprilat on IGF-IR, TGF-β1, and β1 integrin receptor expressions was evaluated. Cells were treated with milimolar concentrations (0.3 and 0.5 mM) of enalapril and enalaprilat for 24 h. The activity of prolidase was determined by colorimetic assay. Collagen biosynthesis was evaluated by radiometric assay. Expression of signaling proteins was evaluated using Western blot. It was found that enalapril- and enalaprilat-dependent increase in prolidase activity and expression was accompanied by parallel increase in collagen biosynthesis. The exposure o...Continue Reading
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