期刊
JOURNAL OF GERIATRIC CARDIOLOGY
卷 19, 期 11, 页码 853-866出版社
SCIENCE PRESS
DOI: 10.11909/j.issn.1671-5411.2022.11.002
关键词
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资金
- National Natural Science Foundation of China [82070309, 8187 0191, 82073838]
- 333 Project of Jiangsu Province
- Lvyangjinfeng Talent Program of Yangzhou
This study found that 7,8-DHF can inhibit cardiac hypertrophy and mitochondrial dysfunction by activating the AMPK signaling pathway, providing a potential agent for the treatment of pathological cardiac hypertrophy.
BACKGROUND Pathological cardiac hypertrophy is a compensated response to various stimuli and is considered a key risk factor for heart failure. 7,8-Dihydroxyflavone (7,8-DHF) is a flavonoid derivative that acts as a small-molecule brain-derived neurotrophic factor mimetic. The present study aimed to explore the potential role of 7,8-DHF in cardiac hypertrophy. METHODS Kunming mice and H9c2 cells were exposed to transverse aortic constriction or isoproterenol (ISO) with or without 7,8-DHF, respectively. F-actin staining was performed to calculate the cell area. Transcriptional levels of hypertrophic markers, including ANP, BNP, and beta-MHC, were detected. Echocardiography, hematoxylin-eosin staining, and transmission electron microscopy were used to examine the cardiac function, histology, and ultrastructure of ventricles. Protein levels of mitochondria-related factors, such as adenosine monophosphate-activated protein kinase (AMPK), and peroxisome proliterator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha), were detected. RESULTS 7,8-DHF inhibited compensated and decompensated cardiac hypertrophy, diminished the cross-sectional area, and alleviated the mitochondrial disorders of cardiomyocytes. Meanwhile, 7,8-DHF reduced the cell size and repressed the mRNA levels of the hypertrophic markers of ISO-treated cardiomyocytes. In addition, 7,8-DHF activated AMPK and PGC-1 alpha signals without affecting the protein levels of mitochondrial dynamics-related molecules. The effects of 7,8-DHF were eliminanted by Compound C, an AMPK inhibitor. CONCLUSIONS These findings suggest that 7,8-DHF inhibited cardiac hypertrophy and mitochondrial dysfunction by activating AMPK signaling, providing a potential agent for the treatment of pathological cardiac hypertrophy.
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