title: Neointima formation in injured hamster carotid artery is effectively prevented by the combination G4120 and quinapril.
abstract: The prevention of neointima formation by the tissue selective angiotensin converting enzyme (ACE) inhibitor quinapril and by the combination quinapril/G4120 (a platelet alpha Ub beta 3 and smooth muscle cell alpha v beta 3 antagonist) was investigated in a hamster carotid artery injury model. Quinapril at 10 mg/kg/day reduced neointima formation by about 45%, 1 and 2 weeks after injury to the artery, i.e. significantly better than the non-tissue selective ACE inhibitor captopril at 100 mg/kg/day. Quinapril did not decrease the early smooth muscle cell (SMC) proliferation in the media, but in agreement with its inhibition of the carotid artery ACE activity by 62%, SMC proliferation was reduced by 70% in the newly forming intima. To improve the inhibition of early medial SMC proliferation, quinapril (10 mg/kg/day) was complemented with G4120 (100 micrograms/kg/h). This combined treatment reduced the proliferation of medial SMCs to about 50% throughout the first week following injury, whereas intima SMC proliferation was reduced by 70% throughout treatment. Accordingly, the drug combination reduced neointima formation more potently than each drug separately by 70%. The disruption of medial elastic laminae, observed in the control and G4120 treated group, was consistently reduced when G4120 was complemented with quinapril. Thus, the present study shows in a hamster model of carotid artery injury, that combining drugs that prevent SMC migration and proliferation via different modes of action can lead to the effective prevention of neointima formation.
authors.affiliation: Center for Molecular and Vascular Biology, University of Leuven, Belgium.
authors.forename: H
authors.initials: H
authors.lastname: Matsuno
authors.forename: J M
authors.initials: JM
authors.lastname: Stassen
authors.forename: L
authors.initials: L
authors.lastname: Moons
authors.forename: J
authors.initials: J
authors.lastname: Vermylen
authors.forename: M F
authors.initials: MF
authors.lastname: Hoylaerts
mesh_terms: D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects*; D020212:Carotid Artery Injuries; D016893:Carotid Stenosis / Q000517:prevention & control; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D000077583:Quinapril; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors; D012016:Reference Values; D013454:Sulfoxides / Q000494:pharmacology*; D044005:Tetrahydroisoquinolines; D017539:Tunica Intima / Q000187:drug effects*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D007546:Isoquinolines; D010456:Peptides, Cyclic; D010980:Platelet Membrane Glycoproteins; D019030:Receptors, Vitronectin; D013454:Sulfoxides; D044005:Tetrahydroisoquinolines; C074915:G 4120; D000077583:Quinapril