The role and mechanism of P2X7R in cirrhotic cardiomyopathy

Zhenhao Shao; Xu Ding; Yiting Zhou; Jiabin Zhou; Yu Luo; Dan Wu; Yufei Dai; Lingling Qian; Ruxing Wang; Zhiming Yu

doi:10.1016/j.molimm.2024.11.007

The role and mechanism of P2X7R in cirrhotic cardiomyopathy

Mol Immunol. 2024 Nov 20:176:49-59. doi: 10.1016/j.molimm.2024.11.007. Online ahead of print.

Authors

Zhenhao Shao¹, Xu Ding¹, Yiting Zhou¹, Jiabin Zhou¹, Yu Luo¹, Dan Wu¹, Yufei Dai¹, Lingling Qian¹, Ruxing Wang¹, Zhiming Yu²

Affiliations

¹ Wuxi Medical Center, Nanjing Medical University, Wuxi, China; The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China; Wuxi People's Hospital, Wuxi, China.
² Wuxi Medical Center, Nanjing Medical University, Wuxi, China; The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China; Wuxi People's Hospital, Wuxi, China. Electronic address: yuzhimi8660@sina.com.

PMID: 39577339
DOI: 10.1016/j.molimm.2024.11.007

Abstract

In the context of liver cirrhosis, the incidence of myocardial inflammation and apoptosis escalates, contributing to the development and progression of cirrhotic cardiomyopathy. The P2X7 receptor, a purinergic receptor linked to inflammatory processes, has been identified in the etiology of a range of autoinflammatory, autoimmune, chronic inflammatory, and metabolic disorders. Despite this, the specific role of the P2X7 receptor in the etiology of cirrhotic cardiomyopathy remains to be elucidated. In our research, a cirrhotic cardiomyopathy animal model was established using mice subjected to bile duct ligation. The expression of the P2X7 receptor was suppressed via intraperitoneal administration of Brilliant Blue G. Cardiac function was evaluated using echocardiographic techniques, while histopathological examination and enzyme-linked immunosorbent assays were employed to assess the presence of inflammation and apoptosis in liver and cardiac tissues. The expression of key proteins, including P2X7, NLRP3, and IL-1β, in the myocardial tissue was quantified by Western blot analysis. Our research has unveiled significant findings in a murine model of liver fibrosis induced by two weeks of bile duct ligation. Notably, we detected escalated levels of liver fibrosis coupled with disruptions in liver blood flow dynamics. Concurrently, there was a marked increase in myocardial inflammation and apoptosis, which adversely affected heart function. Intriguingly, the expression of P2X7 receptors (P2X7R) in cardiac and hepatic tissues was found to be significantly elevated. Targeting and inhibiting the expression of P2X7R not only alleviated myocardial inflammation and apoptosis but also enhanced cardiac performance. Furthermore, this intervention resulted in a noticeable reduction in liver fibrosis. The interplay between the P2X7 and NLRP3 pathways emerges as a pivotal mechanism in the etiology and progression of cirrhotic cardiomyopathy. Our findings suggest that modulating the P2X7-NLRP3 axis could offer promising therapeutic avenues for managing cirrhotic cardiomyopathy.

Keywords: Cirrhotic cardiomyopathy; Inflammation; NLRP3; P2X7R.