Journal of Inflammation Research (Nov 2021)
Regulation of the Immune Microenvironment by an NLRP3 Inhibitor Contributes to Attenuation of Acute Right Ventricular Failure in Rats with Pulmonary Arterial Hypertension
Abstract
Lizhe Guo,1 Gang Qin,1 Yanan Cao,1 Yue Yang,1 Sisi Dai,1 Lu Wang,1 E Wang1,2 1Department of Anesthesiology, Xiangya Hospital Central South University, Changsha, People’s Republic of China; 2National Clinical Research Center for Geriatric Disorders (Xiangya Hospital), Changsha, People’s Republic of ChinaCorrespondence: E WangDepartment of Anesthesiology, Xiangya Hospital Central South University, Xiangya Road #87, Changsha, Hunan, 410008, People’s Republic of ChinaTel/Fax +86-731-84327413Email [email protected]: Right heart failure is the terminal stage of PAH. When PAH patients suffer from pulmonary infection or puerperal infection heart failure often rapidly develops. Low dose of lipopolysaccharide induces rapid right ventricular failure in rats with pulmonary arterial hypertension.Purpose: The objective of this study was to investigate whether the NLRP3 inflammasome mediates disturbance of the ventricular immune microenvironment of PAH rats and promotes right ventricular failure.Methods: Intraperitoneal injection of monocrotaline was used to induce PAH in rats. Right ventricular function was measured via echocardiography before and after the rats were treated with lipopolysaccharide and MCC950. The degree of immune microenvironment disturbance in right ventricular tissue was measured with a rat chemokine and cytokine antibody array, Western blot, flow cytometry and quantitative real-time PCR analysis.Results: After the rats were injected with LPS, they exhibited right ventricular dysfunction and a significant increase in right ventricular tissue inflammation with elevated M1 macrophage proportion. Administration of MCC950 suppressed inflammation and improved right ventricular function. The number of M1 macrophages was decreased after MCC950 treatment. NLRP3 inflammasome inhibition ameliorated LPS-induced changes in the immune microenvironment in the right heart and right ventricular dysfunction in rats with PAH.Conclusion: Selective inhibition of NLRP3 pathway interfered the interaction between hypertrophic cardiomyocytes and macrophages in the initial stage of inflammation and maintained the immune microenvironment balance, eventually contributing to attenuation of LPS-induced acute heart failure in PAH rats.Keywords: pulmonary arterial hypertension, right ventricular failure, NLRP3 inflammasome, inflammation, immune microenvironment
