PMID- 35770948 OWN - NLM STAT- MEDLINE DCOM- 20221021 LR - 20230702 IS - 1551-4005 (Electronic) IS - 1538-4101 (Print) IS - 1551-4005 (Linking) VI - 21 IP - 21 DP - 2022 Nov TI - Astragaloside IV attenuate MI-induced myocardial fibrosis and cardiac remodeling by inhibiting ROS/caspase-1/GSDMD signaling pathway. PG - 2309-2322 LID - 10.1080/15384101.2022.2093598 [doi] AB - Astragalus membranaceus is a traditional Chinese medicine and has been widely used in treating cardiovascular diseases (CVDs), such as asthma, edema, and chest tightness. Astragaloside IV (AS-IV), one of the major active components extracted from Astragalus membranaceus, has a series of pharmacological effects, including inhibiting inflammation, regulating energy metabolism, reducing oxidative stress and apoptosis. However, the effect of AS-IV on myocardial infarction (MI) and the underlying molecular mechanism remains unclear. The purpose of our study is to investigate the effects of AS-IV on MI-induced myocardial fibrosis and cardiac remodeling and to elucidate its underlying mechanisms. MI was induced by ligation of the left anterior descending (LAD) coronary artery. Echocardiography was used to evaluate cardiac function in mice. Pathological changes in cardiac tissues were analyzed with hematoxylin and eosin (H&E) staining, Masson staining, and wheat germ agglutinin (WGA) staining. Immunohistochemistry was used to detect the expression of fibrosis and inflammation-related proteins. Immunofluorescence and flow cytometry were used to detect ROS level. The expressions of alpha-SMA, Collagen I, NLRP3, cleaved cas-1, cleaved IL-18, cleaved IL-beta, GSDMD-N, and cleaved caspase-1 were examined using western blot. The results of cardiac ultrasound showed that AS-IV could improve poor ventricular remodeling, myocardial pathological staining showed that AS-IV could significantly reduce the myocardial fibrosis and myocardial hypertrophy, ROS levels were also significantly reduced, and the protein expression of NLRP3/Caspase-1/GSDMD signaling pathway was remarkably decreased in the AS-IV group. Furthermore, immunohistochemical staining results showed that the expression of myocardial macrophages and neutrophils in AS-IV group decreased significantly, to further investigate whether the reduction of myocardial pyroptosis by AS-IV is related to the regulation of macrophages, in vitro, AS-IV was selected to stimulate bone marrow-derived macrophages (BMDMs). Our findings indicated that AS-IV protective effect of the heart might be related to the reduction of macrophage pyroptosis. These results demonstrate that AS-IV alleviated MI-induced myocardial fibrosis and cardiac remodeling by suppressing ROS/Caspase-1/GSDMD signaling pathway, AS-IV should be further studied in the future. FAU - Zhang, Xiaoqing AU - Zhang X AD - Institute of Cardiovascular Disease of Integrated Traditional Chinese and Western Medicine, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China. FAU - Qu, Huiyan AU - Qu H AD - Department of Cardiovascular Disease, ShuGuang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China. FAU - Yang, Tao AU - Yang T AD - Institute of Cardiovascular Disease of Integrated Traditional Chinese and Western Medicine, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China. FAU - Liu, Qian AU - Liu Q AD - Institute of Cardiovascular Disease of Integrated Traditional Chinese and Western Medicine, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China. FAU - Zhou, Hua AU - Zhou H AUID- ORCID: 0000-0001-6508-7942 AD - Institute of Cardiovascular Disease of Integrated Traditional Chinese and Western Medicine, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China. AD - Department of Cardiovascular Disease, ShuGuang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220630 PL - United States TA - Cell Cycle JT - Cell cycle (Georgetown, Tex.) JID - 101137841 RN - 3A592W8XKE (astragaloside A) RN - EC 3.4.22.36 (Caspase 1) RN - 9007-34-5 (Collagen) RN - TDQ283MPCW (Eosine Yellowish-(YS)) RN - YKM8PY2Z55 (Hematoxylin) RN - 0 (Interleukin-18) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (Reactive Oxygen Species) RN - 0 (Saponins) RN - 0 (Triterpenes) RN - 0 (Wheat Germ Agglutinins) RN - 0 (Gsdma protein, mouse) SB - IM MH - Animals MH - Mice MH - Caspase 1/metabolism MH - Collagen MH - Eosine Yellowish-(YS)/pharmacology MH - Fibrosis MH - Hematoxylin/pharmacology MH - Inflammation MH - Interleukin-18 MH - *Myocardial Infarction/metabolism MH - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism MH - Reactive Oxygen Species MH - Saponins MH - Signal Transduction MH - Triterpenes MH - *Ventricular Remodeling MH - Wheat Germ Agglutinins/metabolism/pharmacology PMC - PMC9586672 OTO - NOTNLM OT - Astragaloside IV OT - cardiac remolding OT - pyroptosis COIS- No potential conflict of interest was reported by the author(s). EDAT- 2022/07/01 06:00 MHDA- 2022/10/20 06:00 PMCR- 2023/06/30 CRDT- 2022/06/30 08:32 PHST- 2022/07/01 06:00 [pubmed] PHST- 2022/10/20 06:00 [medline] PHST- 2022/06/30 08:32 [entrez] PHST- 2023/06/30 00:00 [pmc-release] AID - 2093598 [pii] AID - 10.1080/15384101.2022.2093598 [doi] PST - ppublish SO - Cell Cycle. 2022 Nov;21(21):2309-2322. doi: 10.1080/15384101.2022.2093598. Epub 2022 Jun 30.