Abstract 5393: Increased C-Reactive Protein Expression Exacerbates Left Ventricular Dysfunction and Remodeling after Myocardial Infarction
We have previously reported that elevated serum C-reactive protein (CRP) level after acute myocardial infarction (MI) is associated with adverse outcomes including cardiac rupture, left ventricular (LV) remodeling and cardiac death. Recent experimental studies have shown that CRP per se has some biological properties including proinflammatory and proapoptotic effects, suggesting a pathogenetic role of CRP in the remodeling process after MI. We tested the hypothesis that increased CRP expression would exacerbate adverse LV remodeling after MI through some deleterious effects of CRP. Transgenic mice with human CRP expression (CRP-Tg) and their nontransgenic littermates (Control) underwent proximal ligation of the left coronary artery. Despite increased serum CRP level and cardiac CRP expression in CRP-Tg mice, there was no difference in phenotype between CRP-Tg and control mice before MI. Mortality at five weeks after MI was not different between groups (CRP-Tg: 49%, n=35; Control: 38%, n=40, P=0.28). Five weeks after MI, echocardiography showed that CRP-Tg mice had more LV dilation (LVEDD, CRP-Tg: 5.8 ± 0.1 mm, n=14; Control: 5.2 ± 0.1 mm, n=17, P=0.002) and worse LV function (EF, CRP-Tg: 13 ± 2%, n=14; Control: 19 ± 1%, n=17, P=0.01). Hemodynamic studies indicated that LV +dP/dt (CRP-Tg: 2,947 ± 480 mmHg/s, n=9; Control: 3,788 ± 656 mmHg/s, n=10, P=0.02) and -dP/dt (CRP-Tg: −2,230 ± 48 mmHg/s, n=9; Control: −2,890 ± 161 mmHg/s, n=10, P=0.003) were lower in the CRP-Tg group than in the Control group, although infarct size was comparable. Histological evaluation at one week after MI showed a higher rate of apoptosis in the border zone of infarcted hearts from CRP-Tg mice (CRP-Tg: 1,434 ± 322 per 105 nuclei; Control: 596 ± 112 per 105 nuclei, n=6 for each, P=0.03). Quantitative RT-PCR showed that angiotensin II type 1a receptor and interleukin-6 were upregulated in viable LV samples from CRP-Tg mice compared with controls. Increased CRP expression exacerbates LV dysfunction and remodeling after MI, associated with increased apoptotic rates, increased angiotensin II receptor expression and exaggerated inflammatory response.