Intermedin alleviates pathological cardiac remodeling by upregulating klotho

التفاصيل البيبلوغرافية
العنوان: Intermedin alleviates pathological cardiac remodeling by upregulating klotho
المؤلفون: Chaoshu Tang, Jin-Ling Ren, Jie Du, Mo-Zhi Jia, Yong-Fen Qi, Ya-Rong Zhang, Yao Chen, Lin-Shuang Zhang, Yan-Rong Yu, Yan Liu, Zhong-Ping Ning
المصدر: Pharmacological Research. 159:104926
بيانات النشر: Elsevier BV, 2020.
سنة النشر: 2020
مصطلحات موضوعية: 0301 basic medicine, medicine.medical_specialty, Peptide Hormones, Ventricular Function, Left, Rats, Sprague-Dawley, Ventricular Dysfunction, Left, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, Fibrosis, Ca2+/calmodulin-dependent protein kinase, Internal medicine, Animals, Medicine, Myocytes, Cardiac, Aorta, Abdominal, Phosphorylation, Autocrine signalling, Klotho Proteins, Klotho, Cells, Cultured, Glucuronidase, Mice, Knockout, Pharmacology, Ventricular Remodeling, business.industry, Angiotensin II, Calcineurin, Neuropeptides, medicine.disease, Constriction, Mice, Inbred C57BL, PPAR gamma, Disease Models, Animal, 030104 developmental biology, Endocrinology, 030220 oncology & carcinogenesis, Heart failure, cardiovascular system, Hypertrophy, Left Ventricular, Calcium-Calmodulin-Dependent Protein Kinase Type 2, business, Signal Transduction
الوصف: Cardiac remodeling is accompanied by cardiac hypertrophy, fibrosis, dysfunction, and eventually leading to heart failure. Intermedin (IMD), as a paracrine/autocrine peptide, has a protective effect in cardiovascular diseases. In this study, we elucidated the role and the underlying mechanism of IMD in pathological remodeling. Pathological remodeling mouse models were induced by abdominal aorta constriction for 4 weeks or angiotensin II (Ang II) infusion for 2 weeks in wildtype, IMD-overexpression, IMD-knockout and klotho-knockdown mice. Western blot, real-time PCR, histological staining, echocardiography and hemodynamics were used to detect the role of IMD in cardiac remodeling. Cardiac hypertrophy, fibrosis and dysfunction were significantly aggravated in IMD-knockout mice versus wildtype mice, and the expression of klotho was downregulated. Conversely, cardiac remodeling was alleviated in IMD-overexpression mice, and the expression of klotho was upregulated. Hypertension induced by Ang II infusion rather than abdominal aorta constriction was mitigated by IMD. However, the cardioprotective effect of IMD was blocked in klotho-knockdown mice. Similar results were found in cultured neonatal rat cardiomyocytes, which was pretreated with IMD before Ang II stimulation. Mechanistically, IMD inhibited the phosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and the activity of calcineurin to protect against cardiac hypertrophy through upregulating klotho in vivo and in vitro. Furthermore, peroxisome proliferator-activated receptor γ (PPARγ) might mediate IMD upregulating klotho. In conclusion, pathological remodeling may be alleviated by endogenous IMD, which inhibits the expression of calcineurin and p-CaMKII by upregulating klotho via the PPARγ pathway. It suggested that IMD might be a therapeutic target for heart disease.
تدمد: 1043-6618
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5a0f1ae69c6d51141b6683f95b175934
https://doi.org/10.1016/j.phrs.2020.104926
حقوق: CLOSED
رقم الأكسشن: edsair.doi.dedup.....5a0f1ae69c6d51141b6683f95b175934
قاعدة البيانات: OpenAIRE