Chlorogenic Acid Alleviates Hyperglycemia-Induced Cardiac Fibrosis through Activation of the NO/cGMP/PKG Pathway in Cardiac Fibroblasts
| Autor: | Yingwu Mei, Yan Xu, Yating Wang, Yang Mi, Mingxi Zang, Linhui Qin, RongRong Zhao |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male endocrine system Cardiotonic Agents Nitric Oxide Synthase Type III Cardiac fibrosis Diabetic Cardiomyopathies Pharmacology Nitric Oxide 03 medical and health sciences Western blot In vivo Fibrosis Diabetic cardiomyopathy Gene expression medicine Cyclic GMP-Dependent Protein Kinases Animals Smad3 Protein Cyclic GMP Cell Proliferation 030109 nutrition & dietetics medicine.diagnostic_test business.industry Myocardium Heart Fibroblasts medicine.disease Streptozotocin Mice Inbred C57BL 030104 developmental biology Hyperglycemia cardiovascular system Collagen Chlorogenic Acid business cGMP-dependent protein kinase Food Science Biotechnology medicine.drug |
| Zdroj: | Molecular nutritionfood research. 65(2) |
| ISSN: | 1613-4133 |
| Popis: | Scope Hyperglycemia-induced cardiac fibrosis is one of the main causes of diabetic cardiomyopathy (DM). Chlorogenic acid (CGA) found in many foods has excellent hypoglycemic effectiveness, but it is not known whether CGA can improve DM by inhibiting cardiac fibrosis caused by hyperglycemia. Methods and results Type I diabetic mice were induced by streptozotocin, and after treatment with CGA for 12 weeks, cardiac functions and fibrosis were determined. CGA significantly attenuated hyperglycemia-induced cardiac fibrosis and improved cardiac functions. The mechanism of CGA on fibrotic inhibition was further studied by immunofluorescence, western blot and RNA interference technology in vivo and in vitro. The results showed CGA exerted its anti-fibrotic effects through activating the cyclic GMP/protein kinase G pathway (cGMP/PKG) to block hyperglycemia-induced nuclear translocation of p-Smad2/3, and then inhibiting pro-fibrotic gene expression in cardiac fibroblasts without depending on its hypoglycemic function. Moreover, the data also revealed that CGA increased cGMP level and activated PKG in cardiac fibroblasts by enhancing endothelial nitric oxide synthase activity and NO production. Conclusion Besides lowering blood glucose, CGA also has an independent ability to inhibit cardiac fibrosis. Therefore, long-term consumption of foods rich in CGA for diabetic patients will have great benefits to improve diabetic cardiomyopathy. This article is protected by copyright. All rights reserved. |
| Databáze: | OpenAIRE |
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