{"title":"Intermedin 1-53 Ameliorates Atrial Fibrosis and Reduces Inducibility of\u0000Atrial Fibrillation via TGF-β1/pSmad3 and Nox4 Pathways in a Rat Model\u0000of Heart Failure","authors":"Yinglong Hou, Shenzhou Ma, Ximin Wang, Zhan Li","doi":"10.2174/1574362418666221202152035","DOIUrl":"https://doi.org/10.2174/1574362418666221202152035","url":null,"abstract":"\u0000\u0000Heart failure was induced by MI in rats. Two weeks after MI surgery, rats\u0000with large infarcts (40%) were randomized into control (untreated MI group, n=10) and IMDtreated (n=10) groups. The MI group and Sham group received saline injections. Rats in the IMD\u0000group received IMD1-53, 10nmol/kg/day, intraperitoneally, for four weeks. The AF inducibility\u0000and atrial effective refractory period (AERP) were assessed with the electrophysiology test. Additionally, the left atrial diameter and heart function and hemodynamic test were performed. We detected the area changes of myocardial fibrosis in the left atrium by using Masson staining. To detect the protein expression and mRNA expression of transforming growth factor-β1 (TGF-β1), αSMA, collagen Ⅰ, collagen Ⅲ and NADPH oxidase (Nox4) in myocardial fibroblasts and left atrial,\u0000we used the Western blot method and the SYBR Green I real-time quantitative polymerase chain\u0000reaction (PCR) assay\u0000\u0000\u0000\u0000Compared with the MI group, IMD1-53 treatment decreased left atrial diameter and improved cardiac function, and it also improved the left ventricle end-diastolic pressure (LVEDP).\u0000IMD1-53 treatment attenuated AERP prolongation and reduced atrial fibrillation inducibility in the\u0000IMD group. In vivo, IMD1-53 reduced the left atrial fibrosis content in the heart of MI rats and inhibited mRNA and protein expression of collagen type Ⅰ and Ⅲ. IMD1-53 also inhibited the expression of TGF-β1, α-SMA and Nox4 both in mRNA and protein. In vivo, we found that IMD1-53\u0000inhibited the phosphorylation of Smad3. In vitro, we found that the down-regulation of the expression of Nox4 was partly dependent on the TGF-β1/ALK5 pathway.\u0000\u0000\u0000\u0000IMD1-53 reduced the inducibility and duration of AF and atrial fibrosis in the rats\u0000after the MI operation. The possible mechanisms are associated with the inhibition of TGFβ1/Smad3-related fibrosis and TGF-β1/Nox4 activity. Therefore, IMD1-53 may be a promising\u0000agent as upstream therapy for the prevention of AF.\u0000\u0000\u0000\u0000Compared with the MI group, IMD1-53 treatment decreased left atrial diameter and improved cardiac function, it also improved the left ventrical end diastolic pressure (LVEDP). IMD1-53 treatment attenuated AERP prolongation and reduced atrial fibrillation inducibility in the IMD group. In vivo, the results showed that IMD1-53 reduced the left atrial fibrosis content on the heart of MI rats and inhibited the expression of collagen type Ⅰ and Ⅲ both in mRNA and protein. IMD1-53 also inhibited the expression of TGF-β1, α-SMA and Nox4 both in mRNA and protein. In vivo, the study also showed that IMD1-53 inhibited the phosphorylation of Smad3. In vitro, we found that the down-regulated the expression of Nox4 was partly dependent on TGF-β1/ALK5 pathway.\u0000\u0000\u0000\u0000none.\u0000","PeriodicalId":10868,"journal":{"name":"Current Signal Transduction Therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42431913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}