title: Increased C-reactive protein expression exacerbates left ventricular dysfunction and remodeling after myocardial infarction.
abstract: We previously reported serum C-reactive protein (CRP) elevation after acute myocardial infarction (MI) to be associated with adverse outcomes including cardiac rupture, left ventricular (LV) remodeling, and cardiac death. Experimental studies have indicated that CRP per se has various biological actions including proinflammatory and proapoptotic effects, suggesting a pathogenic role of CRP in the post-MI remodeling process. We tested the hypothesis that increased CRP expression would exacerbate adverse LV remodeling after MI via deleterious effects of CRP. Transgenic mice with human CRP expression (CRP-Tg) and their transgene-negative littermates (control) underwent left coronary artery ligation. There was no apparent difference in phenotypic features between CRP-Tg and control mice before MI. Although mortality and infarct size were similar in the two groups, CRP-Tg mice showed more LV dilation and worse LV function with more prominent cardiomyocyte hypertrophy and fibrosis in the noninfarcted regions after MI than controls. Histological evaluation conducted 1 wk post-MI revealed a higher rate of apoptosis and more macrophage infiltration in the border zones of infarcted hearts from CRP-Tg mice in relation to increased monocyte chemotactic protein (MCP)-1 expression and matrix metalloproteinase (MMP)-9 activity. Increased CRP expression exacerbates LV dysfunction and promotes adverse LV remodeling after MI in mice. The deleterious effect of CRP on post-MI LV remodeling may be associated with increased apoptotic rates, macrophage infiltration, MCP-1 expression, and MMP-9 activity in the border zone.
authors.affiliation: Division of Cardiology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takahashi
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Anzai
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Kaneko
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Mano
authors.forename: Atsushi
authors.initials: A
authors.lastname: Anzai
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Nagai
authors.forename: Takashi
authors.initials: T
authors.lastname: Kohno
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Maekawa
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fukuda
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ogawa
mesh_terms: D000818:Animals; D056988:Anterior Wall Myocardial Infarction / Q000150:complications* / Q000000981:diagnostic imaging / Q000503:physiopathology; D017209:Apoptosis; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism*; D006332:Cardiomegaly / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D018932:Chemokine CCL2 / Q000378:metabolism; D004195:Disease Models, Animal; D005355:Fibrosis; D005838:Genotype; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D013997:Time Factors; D014463:Ultrasonography; D015854:Up-Regulation; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D002097:C-Reactive Protein; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse