Department of Surgery , New England Medical Center Hospitals , Boston , Mass.
Surgery 115 : 495-502 ( 1994)
Abstract
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 alpha-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 .