Exercise Training Attenuates Acute β-Adrenergic Receptor Activation-Induced Cardiac Inflammation via the Activation of AMP-Activated Protein Kinase

• Published in: International journal of molecular sciences Vol. 24; no. 11; p. 9263
• Main Authors: Zhang, Mi, Alemasi, Akehu, Zhao, Mingming, Xu, Wenli, Zhang, Youyi, Gao, Wei, Yu, Haiyi, Xiao, Han
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 25.05.2023; MDPI
• Subjects: acute sympathetic stress; Adrenergic receptors; AMP-activated protein kinase; Apoptosis; Attenuation; Blood pressure; Cardiomyocytes; Cardiovascular diseases; Catecholamines; Chemokines; Cytokines; Enzyme-linked immunosorbent assay; Exercise; exercise training; Fitness training programs; Heart; Heart failure; Heart rate; Histology; Inflammasomes; Inflammation; Kinases; Macrophages; Metformin; Mortality; NLR family, pyrin domain-containing 3; Phosphorylation; Physical fitness; Physical training; Protein kinases; Proteins; Pyrin protein; Receptor mechanisms; Receptors (physiology); Risk factors; Western blotting; Japan; China; NLR family, pyrin domain-containing 3; AMP-activated protein kinase; acute sympathetic stress; exercise training
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24119263

Exercise has proven cardiac benefits, but the underlying mechanisms of exercise that protect the heart from acute sympathetic stress injuries remain unknown. In this study, adult C57BL/6J mice and their AMP-activated protein kinase α2 knockout (AMPKα2 ) littermates were either subjected to 6 weeks of exercise training or housed under sedentary conditions and then treated with or without a single subcutaneous injection of the β-adrenergic receptor (β-AR) agonist isoprenaline (ISO). We investigated the differences in the protective effects of exercise training on ISO-induced cardiac inflammation in wild-type (WT) and AMPKα2 mice using histology, enzyme-linked immunosorbent assay (ELISA) and Western blotting analyses. The results indicated that exercise training alleviated ISO-induced cardiac macrophage infiltration, chemokines and the expression of proinflammatory cytokines in wild-type mice. A mechanism study showed that exercise training attenuated the ISO-induced production of reactive oxygen species (ROS) and the activation of NLR Family, pyrin domain-containing 3 (NLRP3) inflammasomes. In cardiomyocytes, the ISO-induced effects on these processes were inhibited by AMP-activated protein kinase (AMPK) activator (metformin) pretreatment and reversed by the AMPK inhibitor (compound C). AMPKα2 mice showed more extensive cardiac inflammation following ISO exposure than their wild-type littermates. These results indicated that exercise training could attenuate ISO-induced cardiac inflammation by inhibiting the ROS-NLRP3 inflammasome pathway in an AMPK-dependent manner. Our findings suggested the identification of a novel mechanism for the cardioprotective effects of exercise.