期刊
FRONTIERS IN PHARMACOLOGY
卷 13, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2022.919202
关键词
coronary artery disease; cardiac hypertrophy; high-fat diet; metformin; HIF-1 alpha; PPAR-gamma
资金
- National Natural Science Foundation of China [82172170, 81971887, 32071263, 31971194, 82072187]
- Natural Science Foundation of Tianjin [20JCYBJC01260, 20JCYBJC01230, 20JCQNJC01850]
- Tianjin Key Medical Discipline (Specialty) Construction Project
- Key Laboratory of Emergency and Trauma (Hainan Medical University), Ministry of Education [KLET-202018, KLET-201906]
- Fundamental Research Funds for the Central Universities [63211140]
- Undergraduate Innovative Research Program of Nankai University [202010055090]
Metformin attenuates cardiac hypertrophy via the HIF-1 alpha/PPAR-gamma signaling pathway.
Coronary artery disease (CAD) and cardiac hypertrophy (CH) are two main causes of ischemic heart disease. Acute CAD may lead to left ventricular hypertrophy (LVH). Long-term and sustained CH is harmful and can gradually develop into cardiac insufficiency and heart failure. It is known that metformin (Met) can alleviate CH; however, the molecular mechanism is not fully understood. Herein, we used high-fat diet (HFD) rats and H9c2 cells to induce CH and clarify the potential mechanism of Met on CH. We found that Met treatment significantly decreased the cardiomyocyte size, reduced lactate dehydrogenase (LDH) release, and downregulated the expressions of hypertrophy markers ANP, VEGF-A, and GLUT1 either in vivo or in vitro. Meanwhile, the protein levels of HIF-1 alpha and PPAR-gamma were both decreased after Met treatment, and administrations of their agonists, deferoxamine (DFO) or rosiglitazone (Ros), markedly abolished the protective effect of Met on CH. In addition, DFO treatment upregulated the expression of PPAR-gamma, whereas Ros treatment did not affect the expression of HIF-1 alpha. In conclusion, Met attenuates CH via the HIF-1 alpha/PPAR-gamma signaling pathway.
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