Health & Environmental Research Online (HERO)


Print Feedback Export to File
193775 
Journal Article 
Heme oxygenase 1 determines atherosclerotic lesion progression into a vulnerable plaque 
Cheng, C; Noordeloos, AM; Jeney, V; Soares, MP; Moll, F; Pasterkamp, G; Serruys, PW; Duckers, HJ 
2009 
Yes 
Circulation
ISSN: 0009-7322
EISSN: 1524-4539 
119 
23 
3017-3027 
English 
19487598 
WOS:000267016900009 
BACKGROUND: The molecular regulation for the transition from stable to vulnerable plaque remains to be elucidated. Heme oxygenase 1 (HO-1) and its metabolites have been implicated in the cytoprotective defense against oxidative injury in atherogenesis. In this study, we sought to assess the role of HO-1 in the progression toward plaque instability in carotid artery disease in patients and in a murine model of vulnerable plaque development. METHODS AND RESULTS: Atherectomy biopsy from 112 patients with clinical carotid artery disease was collected and stratified according to characteristics of plaque vulnerability. HO-1 expression correlated closely with features of vulnerable human atheromatous plaque (P<0.005), including macrophage and lipid accumulation, and was inversely correlated with intraplaque vascular smooth muscle cells and collagen deposition. HO-1 expression levels correlated with the plaque destabilizing factors matrix metalloproteinase-9, interleukin-8, and interleukin-6. Likewise, in a vulnerable plaque model using apolipoprotein E(-/-) mice, HO-1 expression was upregulated in vulnerable versus stable lesions. HO-1 induction by cobalt protoporphyrin impeded lesion progression into vulnerable plaques, indicated by a reduction in necrotic core size and intraplaque lipid accumulation, whereas cap thickness and vascular smooth muscle cells were increased. In contrast, inhibition of HO-1 by zinc protoporphyrin augmented plaque vulnerability. Plaque stabilizing was prominent after adenoviral transduction of HO-1 compared with sham virus-treated animals, providing proof that the observed effects on plaque vulnerability were HO-1 specific. CONCLUSIONS: Here we demonstrate in a well-defined patient group and a murine vulnerable plaque model that HO-1 induction reverses plaque progression from a vulnerable plaque to a more stable phenotype as part of a compensatory atheroprotective response. 
Atherosclerosis; Coronary disease; Inflammation; Genes; Vasculature 
NAAQS
• ISA-CO (2010 Final Project Page)
     2010 Final