Systolic overload-induced pulmonary inflammation, fibrosis, oxidative stress and heart failure progression through interleukin-1β. (September 2020)

• Record Type: Journal Article
• Authors: Shang, Linlin; Yue, Wenhui; Wang, Dongzhi; Weng, Xinyu; Hall, Michael E.; Xu, Yawei; Hou, Mingxiao; Chen, Yingjie
• Is Part Of: Journal of molecular and cellular cardiology. Volume 146(2020)
• Page Start: 84
• Page End: 94
• Publication Date: 2020-09
• Subjects: Heart failure -- Inflammation -- Fibrosis -- WHO class-2 pulmonary hypertension -- Inflammasome; Cardiology -- Periodicals; Heart Diseases -- Periodicals; Molecular Biology -- Periodicals; Cardiologie -- Périodiques; Cardiology; Electronic journals; Periodicals; 616.12
• DOI: 10.1016/j.yjmcc.2020.07.008
• Languages: English
• ISSNs: 0022-2828

Abstract

Abstract: Chronic heart failure is associated with increased interleukin-1β (IL-1β), leukocyte infiltration, and fibrosis in the heart and lungs. Here we further studied the role of IL-1β in the transition from left heart failure to pulmonary hypertension and right ventricular hypertrophy in mice with existing left heart failure produced by transverse aortic constriction. We demonstrated that transverse aortic constriction-induced heart failure was associated with increased lung inflammation and cleaved IL-1β, and inhibition of IL-1β signaling using blocking antibodies of clone B122 effectively attenuated further decrease of left ventricular systolic function in mice with existing heart failure. We found that inhibition of IL-1β attenuated lung inflammation, inflammasome activation, fibrosis, oxidative stress, and right ventricular hypertrophy. IL-1β blocking antibodies of clone B122 also significantly attenuated lung T cell activation. Together, these data indicate that IL-1β signaling exerts a causal role for heart failure progression, or the transition from left heart failure to lung remodeling and right heart hypertrophy. Graphical abstract: A diagram shows left ventricle pressure overload-induced heart failure causes profound lung leukocyte infiltration, T cell activation, fibrosis, oxidative stress and inflammasome activation and selective inhibition of IL-1β signaling effectively attenuated above changes and the associated right ventricle hypertrophy/fibrosis in mice with existing heart failure. Unlabelled Image Highlights: IL-1β blocking attenuates lung inflammation, fibrosis, as well as RV hypertrophy in mice with existing LV failure. IL-1β blocking antibodies could effectively attenuate heart failure-induced lung T cell activation. Inhibition of IL-1β signaling effectively suppressed lung inflammasome activation.