| Title | alpha(1)-AR overactivation induces cardiac inflammation through NLRP3 inflammasome activation |
| Authors | Xin, Jun-zhou Wu, Ji-min Hu, Guo-min Gu, Hui-jun Feng, Ye-nan Wang, Shuai-xing Cong, Wen-wen Li, Ming-zhe Xu, Wen-li Song, Yao Xiao, Han Zhang, You-yi Wang, Li |
| Affiliation | Shihezi Univ, Med Coll, Affiliated Hosp 1, Dept Cardiol 3, Shihezi 832008, Peoples R China Dept Cardiol, Beijing 100191, Peoples R China Peking Univ, NHC Key Lab Cardiovasc Mol Biol & Regulatory Pept, Beijing Key Lab Cardiovasc Receptors Res, Minist Educ,Hosp 3,Inst Vasc Med,Key Lab Mol Card, Beijing 100191, Peoples R China Peking Univ, Acad Adv Interdisciplinary Studies, Beijing 100871, Peoples R China Shihezi Univ, Dept Physiol, Key Lab Xinjiang Endem & Ethn Dis, Sch Med, Shihezi 832000, Peoples R China |
| Keywords | HEART INHIBITION FIBROSIS |
| Issue Date | Mar-2020 |
| Publisher | ACTA PHARMACOLOGICA SINICA |
| Abstract | Acute sympathetic stress causes excessive secretion of catecholamines and induces cardiac injuries, which are mainly mediated by beta-adrenergic receptors (beta-ARs). However, alpha(1)-adrenergic receptors (alpha(1)-ARs) are also expressed in the heart and are activated upon acute sympathetic stress. In the present study, we investigated whether alpha(1)-AR activation induced cardiac inflammation and the underlying mechanisms. Male C57BL/6 mice were injected with a single dose of alpha(1)-AR agonist phenylephrine (PE, 5 or 10 mg/kg, s.c.) with or without pretreatment with alpha-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 mu M). Moreover, PE-induced NLRP3 inflammasome activation and cardiac inflammation was blocked in Nlrp3(-/-) mice compared with wild-type mice. In conclusion, alpha(1)-AR overactivation induces cardiac inflammation by activating NLRP3 inflammasomes. |
| URI | http://hdl.handle.net/20.500.11897/586185 |
| ISSN | 1671-4083 |
| DOI | 10.1038/s41401-019-0305-x |
| Indexed | SCI(E) Scopus |
| Appears in Collections: | 第三医院 前沿交叉学科研究院 |
