Interleukin‐10 Protects against Oxidative Stress and Endothelial Dysfunction in Mice with Heart Failure

Abstract

Background Inflammation and oxidative stress may contribute to endothelial dysfunction in heart failure. Interleukin-10 (IL-10) inhibits activation of proinflammatory cytokines and reduces oxidative stress. Elevated levels of IL-10 are associated with better endothelial function in patients with coronary artery disease. The purpose of this study was to test the hypothesis that IL-10 protects against endothelial dysfunction in mice with heart failure. Methods and Results IL-10 −/− (IL-10 KO) and wild type mice (WT) underwent coronary artery ligation to produce heart failure (HF). Two weeks after coronary ligation, ventricular function was assessed by echocardiography, and HF mice were defined by >30% left ventricular akinetic zone. Vasomotor function and levels of superoxide (lucigenin chemiluminescence) were examined in aorta. Left ventricular ejection fraction (LVEF) was reduced and left ventricular end-diastolic volume (LVEDV) was greater in HF than sham mice. Lung/ body weight was increased more in HF-IL-10 KO than HF-WT (table). Levels of superoxide were increased in HF, and increased more in HF-IL-10 KO than HF-WT (table). Responses to acetylcholine were modestly impaired in HF, and impaired more in HF-IL-10 KO than HF-WT (table). Responses to nitroprusside were not different between the groups. Conclusion This study suggests that IL-10 protects against development of oxidative stress and endothelial dysfunction during heart failure in mice.