Sunpeng Sheng, Lu Ding, Jinbiao Lai, Zelei Ye, Ru Zhao, Shijia Chen, Jianshe Ma, Junming Fan, Peifeng Jin
{"title":"维替泊芬通过降低心肌成纤维细胞IL-6/STAT3减轻异丙肾上腺素诱导的心肌肥厚","authors":"Sunpeng Sheng, Lu Ding, Jinbiao Lai, Zelei Ye, Ru Zhao, Shijia Chen, Jianshe Ma, Junming Fan, Peifeng Jin","doi":"10.1155/cdr/2852780","DOIUrl":null,"url":null,"abstract":"<p><b>Background:</b> Yes-associated protein (YAP) is a major downstream nuclear coactivator of the Hippo pathway and is activated during myocardial hypertrophy. Verteporfin, a YAP inhibitor, may serve as a potential treatment for myocardial hypertrophy.</p><p><b>Aim:</b> This study was aimed at exploring the role and underlying mechanisms of verteporfin in isoproterenol (ISO)-induced myocardial hypertrophy both in vivo and in vitro.</p><p><b>Methods:</b> GSE18801 directs our focus toward the Hippo pathway role in myocardial hypertrophy. Using an ISO-induced myocardial hypertrophy rat model, YAP expression and localization were observed through Western blot and immunofluorescence. Histopathological analysis was performed to evaluate cardiomyocyte cross-sectional area, and echocardiographic examinations were conducted to assess cardiac function. In vitro, primary neonatal rat cardiomyocytes (NRCMs) were cultured with conditioned medium from cardiac fibroblasts (CF-CM) treated with ISO to observe cell hypertrophy. Mechanistically, GSE203358 dataset analysis, enzyme-linked immunosorbent assay (ELISA), and Western blot were utilized to investigate the effects of ISO and verteporfin on IL-6, STAT3, and p-STAT3 levels in CFs. Subsequently, the changes in the IL-6/STAT3 pathway were evaluated in CFs treated with ISO and verteporfin. Additionally, recombinant IL-6 and IL-6 inhibitor were applied to CMs treated with CF-CM to observe changes in cardiomyocyte size.</p><p><b>Results:</b> Verteporfin improved cardiac performance in rats receiving ISO. In cultured NRCM, both ISO and CF-CM treated with ISO could induce cardiomyocyte hypertrophy. Verteporfin did not attenuate ISO-induced cardiomyocyte hypertrophy. However, it could attenuate hypertrophy induced by the CF-CM treated with ISO. GSE203358 indicated the involvement of the IL-6/STAT3 pathway in the presence of verteporfin in CFs. Additionally, verteporfin reduces IL-6 production in cultured CFs subjected to ISO treatment. Notably, the effects of verteporfin on NRCM were reversed by IL-6.</p><p><b>Conclusions:</b> Verteporfin protects the heart against ISO-induced myocardial hypertrophy by regulating IL-6/STAT3 in cardiac fibroblasts.</p>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2025 1","pages":""},"PeriodicalIF":3.4000,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/cdr/2852780","citationCount":"0","resultStr":"{\"title\":\"Verteporfin Mitigates Isoproterenol-Induced Myocardial Hypertrophy by Attenuating IL-6/STAT3 in Cardiac Fibroblasts\",\"authors\":\"Sunpeng Sheng, Lu Ding, Jinbiao Lai, Zelei Ye, Ru Zhao, Shijia Chen, Jianshe Ma, Junming Fan, Peifeng Jin\",\"doi\":\"10.1155/cdr/2852780\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><b>Background:</b> Yes-associated protein (YAP) is a major downstream nuclear coactivator of the Hippo pathway and is activated during myocardial hypertrophy. Verteporfin, a YAP inhibitor, may serve as a potential treatment for myocardial hypertrophy.</p><p><b>Aim:</b> This study was aimed at exploring the role and underlying mechanisms of verteporfin in isoproterenol (ISO)-induced myocardial hypertrophy both in vivo and in vitro.</p><p><b>Methods:</b> GSE18801 directs our focus toward the Hippo pathway role in myocardial hypertrophy. Using an ISO-induced myocardial hypertrophy rat model, YAP expression and localization were observed through Western blot and immunofluorescence. Histopathological analysis was performed to evaluate cardiomyocyte cross-sectional area, and echocardiographic examinations were conducted to assess cardiac function. In vitro, primary neonatal rat cardiomyocytes (NRCMs) were cultured with conditioned medium from cardiac fibroblasts (CF-CM) treated with ISO to observe cell hypertrophy. Mechanistically, GSE203358 dataset analysis, enzyme-linked immunosorbent assay (ELISA), and Western blot were utilized to investigate the effects of ISO and verteporfin on IL-6, STAT3, and p-STAT3 levels in CFs. Subsequently, the changes in the IL-6/STAT3 pathway were evaluated in CFs treated with ISO and verteporfin. Additionally, recombinant IL-6 and IL-6 inhibitor were applied to CMs treated with CF-CM to observe changes in cardiomyocyte size.</p><p><b>Results:</b> Verteporfin improved cardiac performance in rats receiving ISO. In cultured NRCM, both ISO and CF-CM treated with ISO could induce cardiomyocyte hypertrophy. Verteporfin did not attenuate ISO-induced cardiomyocyte hypertrophy. However, it could attenuate hypertrophy induced by the CF-CM treated with ISO. GSE203358 indicated the involvement of the IL-6/STAT3 pathway in the presence of verteporfin in CFs. Additionally, verteporfin reduces IL-6 production in cultured CFs subjected to ISO treatment. 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Verteporfin Mitigates Isoproterenol-Induced Myocardial Hypertrophy by Attenuating IL-6/STAT3 in Cardiac Fibroblasts
Background: Yes-associated protein (YAP) is a major downstream nuclear coactivator of the Hippo pathway and is activated during myocardial hypertrophy. Verteporfin, a YAP inhibitor, may serve as a potential treatment for myocardial hypertrophy.
Aim: This study was aimed at exploring the role and underlying mechanisms of verteporfin in isoproterenol (ISO)-induced myocardial hypertrophy both in vivo and in vitro.
Methods: GSE18801 directs our focus toward the Hippo pathway role in myocardial hypertrophy. Using an ISO-induced myocardial hypertrophy rat model, YAP expression and localization were observed through Western blot and immunofluorescence. Histopathological analysis was performed to evaluate cardiomyocyte cross-sectional area, and echocardiographic examinations were conducted to assess cardiac function. In vitro, primary neonatal rat cardiomyocytes (NRCMs) were cultured with conditioned medium from cardiac fibroblasts (CF-CM) treated with ISO to observe cell hypertrophy. Mechanistically, GSE203358 dataset analysis, enzyme-linked immunosorbent assay (ELISA), and Western blot were utilized to investigate the effects of ISO and verteporfin on IL-6, STAT3, and p-STAT3 levels in CFs. Subsequently, the changes in the IL-6/STAT3 pathway were evaluated in CFs treated with ISO and verteporfin. Additionally, recombinant IL-6 and IL-6 inhibitor were applied to CMs treated with CF-CM to observe changes in cardiomyocyte size.
Results: Verteporfin improved cardiac performance in rats receiving ISO. In cultured NRCM, both ISO and CF-CM treated with ISO could induce cardiomyocyte hypertrophy. Verteporfin did not attenuate ISO-induced cardiomyocyte hypertrophy. However, it could attenuate hypertrophy induced by the CF-CM treated with ISO. GSE203358 indicated the involvement of the IL-6/STAT3 pathway in the presence of verteporfin in CFs. Additionally, verteporfin reduces IL-6 production in cultured CFs subjected to ISO treatment. Notably, the effects of verteporfin on NRCM were reversed by IL-6.
Conclusions: Verteporfin protects the heart against ISO-induced myocardial hypertrophy by regulating IL-6/STAT3 in cardiac fibroblasts.
期刊介绍：
Cardiovascular Therapeutics (formerly Cardiovascular Drug Reviews) is a peer-reviewed, Open Access journal that publishes original research and review articles focusing on cardiovascular and clinical pharmacology, as well as clinical trials of new cardiovascular therapies. Articles on translational research, pharmacogenomics and personalized medicine, device, gene and cell therapies, and pharmacoepidemiology are also encouraged.
Subject areas include (but are by no means limited to):
Acute coronary syndrome
Arrhythmias
Atherosclerosis
Basic cardiac electrophysiology
Cardiac catheterization
Cardiac remodeling
Coagulation and thrombosis
Diabetic cardiovascular disease
Heart failure (systolic HF, HFrEF, diastolic HF, HFpEF)
Hyperlipidemia
Hypertension
Ischemic heart disease
Vascular biology
Ventricular assist devices
Molecular cardio-biology
Myocardial regeneration
Lipoprotein metabolism
Radial artery access
Percutaneous coronary intervention
Transcatheter aortic and mitral valve replacement.
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