BOTH LISINOPRIL AND VERAPAMIL REDUCED PLATELET-DERIVED GROWTH FACTOR-A CHAIN MESSENGER-RNA LEVELS IN HUMAN SAPHENOUS-VEIN ENDOTHELIAL-CELLSSTIMULATED BY THROMBIN

Background. Both angiotensin-converting enzyme inhibitors and calcium channel blockers decrease postinjury intimal thickening in vivo, but t heir mechanisms of inhibitory action are unclear. Expression of the ge ne 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 his study, we tested whether lisinopril, an angiotensin-converting enzyme inhibitor, or verapamil, a calcium c hannel blocker, would suppress the PDGF gene expression in stimulated human saphenous vein ECs. Methods. Drugs were added to replicate EC cu ltures 30 minutes before adding 10 units/ml alpha-thrombin. Changes in PDGF-A chain mRNA levels were measured by Northern blot analysis or r everse transcription-polymerase chain reaction method. PDGF-AA homodim er in conditioned media was measured by ELISA. Results. Lisinopril att enuated the induction by thrombin of PDGF-A chain mRNA levels signific antly 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 m edium. Verapamil also reduced thrombin induction of PDGF-A mRNA levels significantly at a dose of 10(-5) mol/L (p < 0.05) and appeared to re duce PDGF-AA homidimer secretion. Conclusions. These data suggest that one means by which lisinopril and verapamil both suppress intimal thi ckening might be inhibition of PDGF-A chain gene expression in ECs reg rowing over vessel injury areas that are sites of thrombin generation.