Abstract 360: Genetic Deletion of IL-6 Ameliorates Left Ventricular Dysfunction and Remodeling after a Reperfused Myocardial Infarction
Although myocardial expression of interleukin (IL)-6 increases after acute myocardial infarction (MI), its role in left ventricular (LV) remodeling remains controversial. We subjected IL-6 knockout (IL-6−/−, n=8) and wild-type (WT, n=8) mice to a 30-min coronary occlusion followed by reperfusion. Echocardiography was performed before (BSL1) and at 48 h (BSL2), 4 wks, and 8 wks after MI. Mice were sacrificed after 8 wks of follow-up. Histologic infarct size was similar in both groups. Compared with infarcted WT mice, infarcted IL-6−/− mice exhibited improved global and regional LV systolic function as evidenced by improved LV ejection fraction (39.6±1.3% vs. 47.6±3.5% in WT and IL-6−/− mice, respectively, P<0.05, Fig⇓) and infarct wall (30±3% vs. 47±3% in WT and IL-6−/− mice, respectively, P<0.05) and posterior wall (48±4% vs. 65±3% in WT and IL-6−/− mice, respectively, P<0.05) systolic thickening fraction. IL-6−/− mice also exhibited improved remodeling as evidenced by lower LV posterior wall thickness in diastole (0.90±0.05 mm vs. 0.72±0.02 mm in WT and IL-6−/− mice, respectively, P<0.05, Fig⇓), lower LV mass by echocardiography (127±1.6 mg vs. 108±2.5 mg in WT and IL-6−/− mice, respectively, P<0.05, Fig⇓), and lower heart weight at necropsy. Myocyte hypertrophy in the noninfarcted zone was attenuated in IL-6−/− mice compared with WT mice (Fig⇓). The amelioration of postinfarct LV dysfunction and remodeling in IL-6−/− mice indicates that IL-6 plays a deleterious role in LV remodeling after a reperfused MI. These findings may have potential therapeutic implications for the management of patients with acute MI.