Abstract 15693: Genetic Deletion of Interleukin-6 Attenuates Left Ventricular Dysfunction and Remodeling After a Reperfused Myocardial Infarction
Introduction: Interleukin-6 (IL-6) is a proinflammatory cytokine, which is known to have a close association with cardiovascular diseases. Although myocardial expression of interleukin (IL)-6 increases after acute myocardial infarction (MI), its role in left ventricular (LV) remodeling and pathogenesis of heart failure remains unclear.
Hypothesis: We hypothesized that the absence of IL-6 will have a favorable impact on LV remodeling after a reperfused MI.
Methods: Because most heart attacks in humans are followed by spontaneous or interventional reperfusion, we used a model of reperfused MI. Age-matched male C57BL/6 control mice and IL-6 knockout (KO) mice were subjected to a 30-min occlusion of the LAD coronary artery followed by reperfusion. Cardiac structure and function were serially assessed by echocardiography at baseline (4 d before MI) and at 48 h and 35 d after MI. Mice were sacrificed after 35 days for histological and biochemical assessments.
Results: At 48 h post-MI, ejection fraction (EF) was similarly and significantly reduced in both groups compared with baseline (Figure), indicating that the ischemic injury was comparable between groups. However, 35 d after MI, IL-6 KO mice exhibited significantly greater EF compared with control mice. Moreover, LV end-diastolic volume was significantly smaller in IL-6 KO mice (Figure), indicating superior remodeling.
Conclusions: The amelioration of postinfarct LV dysfunction and remodeling in IL-6 KO mice indicates that IL-6 plays a deleterious role in myocardial healing after a reperfused MI. Modulation of IL-6 signaling may therefore have therapeutic potential for patients after MI at risk for adverse remodeling and development of heart failure.
Author Disclosures: A. Samanta: None. G. Cheng: None. A. Davani: None. M. Girgis: None. L. Chen: None. K. Choksi: None. L. Zhao: None. R.J. Vincent: None. J. Hauptman: None. B. Dawn: None.
- © 2014 by American Heart Association, Inc.