title: ACE inhibitor quinapril reduces the arterial expression of NF-kappaB-dependent proinflammatory factors but not of collagen I in a rabbit model of atherosclerosis.
abstract: Increasing evidence supports an association between inflammation and plaque rupture. Macrophages and vascular smooth muscle cells are a source of cytokines and growth factors, which contribute to ongoing inflammation during atherogenesis. In a rabbit model of atherosclerosis, we evaluated the effect of the ACE inhibitor quinapril on different parameters implicated in the pathogenesis of the plaque, such as the presence of chemokines (interleukin-8, monocyte chemoattractant protein-1), collagen I, and vascular smooth muscle cell proliferation (PDGF-B). Since nuclear factor kappaB (NF-kappaB) has been implicated in the control of chemokine transcription and cell proliferation, we also investigated its activation and localization in the lesion. Quinapril administration for 28 days caused a down-regulation in arterial expression of interleukin-8 and monocyte chemoattractant protein-1 (mRNA and protein). However, collagen I expression (mRNA and protein) was not modified. PDGF-B expression was reduced in both the intima and the media. Active NF-kappaB, found in both macrophages and vascular smooth muscle cells, was also reduced by quinapril. Nevertheless, no significant changes were noted in the mild neointima formation, although a certain trend toward normalization was found in the quinapril-treated group. In conclusion, our results show that quinapril treatment attenuates several parameters associated with inflammation within the atherosclerotic lesions that are controlled by NF-kappaB, although it has no effect on collagen I expression. Both effects could contribute to the stabilization of the atherosclerotic plaque.
authors.affiliation: Research Laboratory, Fundación Jiménez Díaz, Autonoma University, Madrid, Spain.
authors.forename: M A
authors.initials: MA
authors.lastname: Hernández-Presa
authors.forename: C
authors.initials: C
authors.lastname: Bustos
authors.forename: M
authors.initials: M
authors.lastname: Ortego
authors.forename: J
authors.initials: J
authors.lastname: Tuñón
authors.forename: L
authors.initials: L
authors.lastname: Ortega
authors.forename: J
authors.initials: J
authors.lastname: Egido
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000378:metabolism; D001161:Arteriosclerosis / Q000276:immunology / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D003094:Collagen / Q000378:metabolism*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D016209:Interleukin-8 / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology*; D008264:Macrophages / Q000276:immunology; D016328:NF-kappa B / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D000077583:Quinapril; D011817:Rabbits; D044005:Tetrahydroisoquinolines
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D018932:Chemokine CCL2; D016209:Interleukin-8; D007546:Isoquinolines; D016328:NF-kappa B; D010982:Platelet-Derived Growth Factor; D044005:Tetrahydroisoquinolines; D003094:Collagen; D002784:Cholesterol; D000077583:Quinapril