| Title | Glibenclamide alleviates beta adrenergic receptor activation-induced cardiac inflammation |
| Authors | Cao, Ning Wang, Jing-jing Wu, Ji-min Xu, Wen-li Wang, Rui Chen, Xian-da Feng, Ye-nan Cong, Wen-wen Zhang, You-yi Xiao, Han Dong, Er-dan |
| Affiliation | Peking Univ Third Hosp, Dept Cardiol, Beijing 100191, Peoples R China Peking Univ Third Hosp, Inst Vasc Med, Beijing 100191, Peoples R China NHC Key Lab Cardiovasc Mol Biol & Regulatory Pept, Beijing 100191, Peoples R China Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing 100191, Peoples R China Beijing Key Lab Cardiovasc Receptors Res, Beijing 100191, Peoples R China Tianjin First Ctr Hosp, Emergency Med Res Inst, Intens Care Unit, Tianjin 300192, Peoples R China Shihezi Univ, Dept Physiol, Minist Of Educ, Key Lab Xinjiang Endem & Ethn Dis, Shihezi 832000, Peoples R China |
| Keywords | SULFONYLUREAS STIMULATION |
| Issue Date | Aug-2021 |
| Publisher | ACTA PHARMACOLOGICA SINICA |
| Abstract | beta-Adrenergic receptor (beta-AR) overactivation is a major pathological factor associated with cardiac diseases and mediates cardiac inflammatory injury. Glibenclamide has shown anti-inflammatory effects in previous research. However, it is unclear whether and how glibenclamide can alleviate cardiac inflammatory injury induced by beta-AR overactivation. In the present study, male C57BL/6J mice were treated with or without the beta-AR agonist isoprenaline (ISO) with or without glibenclamide pretreatment. The results indicated that glibenclamide alleviated ISO-induced macrophage infiltration in the heart, as determined by Mac-3 staining. Consistent with this finding, glibenclamide also inhibited ISO-induced chemokines and proinflammatory cytokines expression in the heart. Moreover, glibenclamide inhibited ISO-induced cardiac fibrosis and dysfunction in mice. To reveal the protective mechanism of glibenclamide, the NLRP3 inflammasome was further analysed. ISO activated the NLRP3 inflammasome in both cardiomyocytes and mouse hearts, but this effect was alleviated by glibenclamide pretreatment. Furthermore, in cardiomyocytes, ISO increased the efflux of potassium and the generation of ROS, which are recognized as activators of the NLRP3 inflammasome. The ISO-induced increases in these processes were inhibited by glibenclamide pretreatment. Moreover, glibenclamide inhibited the cAMP/PKA signalling pathway, which is downstream of beta-AR, by increasing phosphodiesterase activity in mouse hearts and cardiomyocytes. In conclusion, glibenclamide alleviates beta-AR overactivation-induced cardiac inflammation by inhibiting the NLRP3 inflammasome. The underlying mechanism involves glibenclamide-mediated suppression of potassium efflux and ROS generation by inhibiting the cAMP/PKA pathway. |
| URI | http://hdl.handle.net/20.500.11897/623177 |
| ISSN | 1671-4083 |
| DOI | 10.1038/s41401-021-00734-0 |
| Indexed | SCI(E) |
| Appears in Collections: | 第三医院 |
