Hong Fang, Omer Cavdar, Zhiping Yao, Xuewei Zhu, Yi Shen, Chi Liu
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引用次数: 0
Abstract
Previous studies suggest that ferroptosis is involved in cardiovascular diseases. The aim of the present study is to investigate the causal relationship between angiotensin II type 1 and type 2 receptors (AT1/2R) activities and mitochondrial dysfunction in induction of cardiomyocyte ferroptosis. Human AC16 cardiomyocytes were first pre-treated with an AT1/2R blockers, before stimulated with angiotensin II (Ang II) for 24 h. The redox status of the cardiomyocytes were assessed by measuring the cellular malondialdehyde (MDA), superoxide dismutase (SOD), and Nicotinamide-adenine dinucleotide phosphate, (NADPH) levels using biochemical methods. Mitochondrial reactive oxygen specifics (mitROS), mitochondrial memebrane potential, and Fe2+ levels were determined using flow cytometry. The signaling pathways, including the glutathione peroxidase 4 (GPX4), heme oxygenase-1 (HO-1), sirtuin1, and ferroptosis suppressor protein 1 (FSP1)-coenzyme Q10 (CoQ10) pathways, were evaluated using western blotting. Our results demonstrated that Ang II significantly elevated the levels of MDA, Fe2+, mitoROS, and FtMt and markedly reduced SOD, NADPH, mitochondrial membrane potential, GPX4, HO-1, Sirt1, SFXN1, Nrf2, and FSP1 levels in cardiomyocyte, which were reversed by blockade of AT1/2R. Our results suggest that AT1/2R signaling can induce myocardial ferroptosis by impairing mitochondrial function via multiple signaling pathways, including the cyst (e)ine /GSH/GPX4 axis and FSP1/coenzyme Q10 (CoQ10) axis.
期刊介绍：
Journal of Human Hypertension is published monthly and is of interest to health care professionals who deal with hypertension (specialists, internists, primary care physicians) and public health workers. We believe that our patients benefit from robust scientific data that are based on well conducted clinical trials. We also believe that basic sciences are the foundations on which we build our knowledge of clinical conditions and their management. Towards this end, although we are primarily a clinical based journal, we also welcome suitable basic sciences studies that promote our understanding of human hypertension.
The journal aims to perform the dual role of increasing knowledge in the field of high blood pressure as well as improving the standard of care of patients. The editors will consider for publication all suitable papers dealing directly or indirectly with clinical aspects of hypertension, including but not limited to epidemiology, pathophysiology, therapeutics and basic sciences involving human subjects or tissues. We also consider papers from all specialties such as ophthalmology, cardiology, nephrology, obstetrics and stroke medicine that deal with the various aspects of hypertension and its complications.
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