?1-AR overactivation induces cardiac inflammation through NLRP3 inflammasome activation.

ABSTRACT: Acute sympathetic stress causes excessive secretion of catecholamines and induces cardiac injuries, which are mainly mediated by ?-adrenergic receptors (?-ARs). However, ?1-adrenergic receptors (?1-ARs) are also expressed in the heart and are activated upon acute sympathetic stress. In the present study, we investigated whether ?1-AR activation induced cardiac inflammation and the underlying mechanisms. Male C57BL/6 mice were injected with a single dose of ?1-AR agonist phenylephrine (PE, 5 or 10?mg/kg, s.c.) with or without pretreatment with ?-AR antagonist prazosin (5?mg/kg, s.c.). PE injection caused cardiac dysfunction and cardiac inflammation, evidenced by the increased expression of inflammatory cytokine IL-6 and chemokines MCP-1 and MCP-5, as well as macrophage infiltration in myocardium. These effects were blocked by prazosin pretreatment. Furthermore, PE injection significantly increased the expression of NOD-like receptor protein 3 (NLRP3) and the cleavage of caspase-1 (p20) and interleukin-18 in the heart; similar results were observed in both Langendorff-perfused hearts and cultured cardiomyocytes following the treatment with PE (10??M). Moreover, PE-induced NLRP3 inflammasome activation and cardiac inflammation was blocked in Nlrp3-/- mice compared with wild-type mice. In conclusion, ?1-AR overactivation induces cardiac inflammation by activating NLRP3 inflammasomes.

SUBMITTER: Xin JZ 

PROVIDER: S-EPMC7468364 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature