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Abstract-Serum C-reactive protein (CRP) elevation predicts the development of heart failure in patients with hypertension. CRP activates macrophages and enhances oxidative stress. We hypothesize that CRP itself has a pathogenic role in the development of pressure overload-induced cardiac remodeling. Transgenic mice with human CRP overexpression (CRPtg) and nontransgenic littermates (CON) were subjected to transverse aortic constriction (TAC/CRPtg and TAC/CON) or sham operation (Sham/CRPtg and Sham/CON). One week after operation, in TAC/CRPtg, myocardial mRNA levels of interleukin (IL)-6, CD68, glutathione peroxidase-3 (GPx3), 47-kDa ␣-subunit of nicotinamide adenine dinucleotide phosphate oxidase (p47 phox ), and collagen-I, the number of infiltrating Mac-2-positive macrophages, nuclear localization of phosphorylated NF-B/p65 (p-p65) in cardiomyocytes, nuclear NF-B-DNA-binding activity, and reactive oxygen species (ROS) content were increased compared to those in TAC/CON. Cardiac fibrosis was more prominent in TAC/CRPtg compared to TAC/CON. Four weeks after operation, heart and lung weights, cardiomyocyte cross-sectional area, and the extent of cardiac fibrosis were greater in TAC/CON than in Sham/CON, and these differences were further augmented in TAC/CRPtg compared to TAC/CON. Left ventricular (LV) fractional shortening was less and LV end-diastolic pressure was higher in TAC/CRPtg than in TAC/CON. Myocardial mRNA levels of angiotensin type 1 receptor, atrial natriuretic factor, GPx3, p47 phox , collagen-I, and transforming growth factor (TGF)-␤1, the protein level of TGF-␤1, and the numbers of Mac-2-positive macrophages and p-p65-positive cells were higher in TAC/CRPtg than in TAC/CON. In conclusion, CRP itself may have a pathogenic role in the development of pressure overload-induced cardiac remodeling, possibly through enhanced inflammation and oxidative stress. C -reactive protein (CRP), which is an acute-phase protein, has been regarded as a risk factor or biomarker for cardiovascular disease, including coronary artery disease, hypertension, and heart failure. Elevation of serum CRP is associated with left ventricular (LV) dysfunction and is a predictor of mortality and morbidity in patients with heart failure, independent of ischemic/nonischemic etiology and other established cardiovascular risk factors. 1-3 Laboratory evidence suggests that CRP not only serves as a biomarker but also upregulates the angiotensin type 1 receptor (AT 1 R), 4 stimulates proinflammatory cytokine production, 5 and attenuates nitric oxide (NO) production. 6 In addition, pathological examination of endomyocardial biopsies in patients with dilated cardiomyopathy revealed that CRP is frequently present in the myocardium and colocalizes with complement and macrophages. 7 Furthermore, CRP is reported to promote fibrosis and inflammation in angiotensin II-induced cardiac remodeling. 8 These findings suggest that CRP itself may play some role in the development of LV dysfunction and remodeling.Human CRP is mainly produced in the ...

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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.

A 62-year-old man was admitted to our emergency department owing to prolonged chest pain that had lasted for 3 h. An electrocardiogram showed ST elevation in leads I, aVL, and V1-6, and the patient's laboratory revealed elevated myocardial necrosis marker levels. Emergency coronary angiography showed total occlusion of the proximal left anterior descending coronary artery. Subsequent percutaneous coronary intervention was performed by balloon angioplasty followed by stent implantation, and the patient showed improvement. However, echocardiographic examination 2 weeks after the percutaneous coronary intervention showed a thrombus (40 × 14 mm) in the apex of the left ventricle. In addition to dual antiplatelet therapy, apixaban was administered as anticoagulant therapy for the left ventricular thrombus. The size of the thrombus gradually decreased, and magnetic resonance imaging performed approximately 6 weeks after the initial apixaban administration showed no thrombus without a thromboembolic event. This case demonstrates that left ventricular thrombus can be resolved with apixaban treatment. Apixaban may be an effective alternative to vitamin K antagonist for some patients with acute myocardial infarction complicated by left ventricular thrombus.