Both lisinopril and verapamil reduced platelet-derived growth factor-A chain mRNA levels in human saphenous vein endothelial cells stimulated by thrombin.
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.
Yamaguchi
M
M
Department of Surgery, New England Medical Center Hospitals, Boston, Mass.
Gallati
H
H
Baur
W
W
Cruess
D F
DF
Sharefkin
J B
JB
D001483:Base Sequence; D017077:Culture Media, Conditioned / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D017706:Lisinopril / Q000494:pharmacology*; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000235:genetics; D010982:Platelet-Derived Growth Factor / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D012501:Saphenous Vein / Q000166:cytology / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology*
D017077:Culture Media, Conditioned; D015345:Oligonucleotide Probes; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; C075278:platelet-derived growth factor A; D014700:Verapamil; D017706:Lisinopril; D013917:Thrombin