The TIR/BB-loop mimetic AS-1 prevents Ang II-induced hypertensive cardiac hypertrophy via NF-κB dependent downregulation of miRNA-143
Autor: | Ping Yang, Zhongqun Wang, Jinchuan Yan, Peijing Liu, Yi Lu, Lin Wang, Rui Chen, Juan Song, Chen Qiao, Chen Shao, Qifei Xie |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Male medicine.medical_specialty P50 Pyrrolidines MAP Kinase Signaling System lcsh:Medicine Down-Regulation Cardiomegaly 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation In vivo Internal medicine medicine Myocyte Animals Myocytes Cardiac Phosphorylation lcsh:Science Multidisciplinary Chemistry Angiotensin II lcsh:R NF-kappa B NF-κB Valine medicine.disease Rats Mice Inbred C57BL MicroRNAs 030104 developmental biology Endocrinology Blood pressure Animals Newborn Gene Expression Regulation Heart failure Hypertension cardiovascular system lcsh:Q hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery |
Zdroj: | Scientific Reports, Vol 9, Iss 1, Pp 1-10 (2019) |
ISSN: | 2045-2322 |
Popis: | Untreated pathological cardiac hypertrophy, which can be caused by sustained systemic hypertension, may lead to heart failure. In the present study, we investigated whether AS-1 had attenuating effects on hypertension-induced cardiac hypertrophy, and whether this process was mediated by the regulation of miRNA-143. To induce the hypertrophic response in vitro, cardiomyocytes were stimulated with Ang II for 24hs. AS-1 administration strongly attenuated Ang II-induced hypertrophic response of cardiomyocytes. Chronical infusion of Ang II via implanted osmotic mini-pump induced increased blood pressure and cardiac hypertrophy in vivo. AS-1 administration attenuated hypertension-induced cardiac hypertrophy by, at least in part, inhibin of MAPK signaling. We observed, for the first time, upregulated expression of miRNA-143 in Ang II-induced cardiomyocytes, and inhibition of miRNA-143 significantly reduced the Ang II-induced hypertrophic responses. Importantly, AS-1 administration diminished the Ang II-induced upregulation of miRNA-143. Overexpression of miRNA-143 abolished the attenuating effects of AS-1 on Ang II-induced hypertrophic response of cardiomyocytes. Additionally, AS-1 administration abrogates Ang II-induced nuclear translocation of p50 NF-κB subunit in hypertrophic cardiomyocytes. Application of NF-κB inhibitor significantly suppressed Ang II-induced upregulation of miRNA-143. Our data suggest a novel mechanism by which AS-1 attenuates Ang II-induced hypertrophic response through downregulation miRNA-143 expression in a NF-κB-dependent manner. |
Databáze: | OpenAIRE |
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