Background. Both angiotensin-converting enzyme inhibitors and calcium channel blockers decrease postinjury intimal thickening in vivo, but their mechanisms of inhibitory action are unclear. Expression of the gene for platelet-derived growth factor (PDGF), a smooth-muscle mitogen, in endothelial cells (ECs) after vessel injury has been postulated to cause intimal thickening. In this study, we tested whether lisinopril, an angiotensin-converting enzyme inhibitor, or verapamil, a calcium channel blocker, would suppress the PDGF gene expression in stimulated human saphenous vein ECs. Methods. Drugs were added to replicate EC cultures 30 minutes before adding 10 units/ml α-thrombin. Changes in PDGF-A chain mRNA levels were measured by Northern blot analysis or reverse transcription- polymerase chain reaction method. PDGF-AA homodimer in conditioned media was measured by ELISA. Results. Lisinopril attenuated the induction by thrombin of PDGF-A chain mRNA levels significantly in human ECs at doses of 10-6 mol/L and 10-5 mol/L (p < 0.05) and appeared to decrease PDGF-AA homodimer released in conditioned medium. Verapamil also reduced thrombin induction of PDGF-A chain mRNA levels significantly at a dose of 10-5 mol/L (p < 0.05) and appeared to reduce PDGF-AA homodimer secretion. Conclusions. These data suggest that one means by which lisinopril and verapamil both suppress intimal thickening might be inhibition of PDGF-A chain gene expression in ECs regrowing over vessel injury areas that are sites of thrombin generation.
|Number of pages||8|
|State||Published - 1994|