Open AccessHaemin attenuates intermittent hypoxia‐induced cardiac injury via inhibiting mitochondrial fission
Author(s) -
Han Qian,
Li Guihua,
Ip Mary SiuMan,
Zhang Yuelin,
Zhen Zhe,
Mak Judith ChoiWo,
Zhang Nuofu
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13560
Subject(s) - mitochondrial fission , apoptosis , tunel assay , mfn2 , mitochondrion , cardiac function curve , mitochondrial fusion , medicine , microbiology and biotechnology , endocrinology , pharmacology , chemistry , biology , mitochondrial dna , biochemistry , heart failure , gene
Obstructive sleep apnoea ( OSA ) characterized by intermittent hypoxia ( IH ) is closely associated with cardiovascular diseases. IH confers cardiac injury via accelerating cardiomyocyte apoptosis, whereas the underlying mechanism has remained largely enigmatic. This study aimed to explore the potential mechanisms involved in the IH ‐induced cardiac damage performed with the IH ‐exposed cell and animal models and to investigate the protective effects of haemin, a potent haeme oxygenase‐1 ( HO ‐1) activator, on the cardiac injury induced by IH . Neonatal rat cardiomyocyte ( NRC ) was treated with or without haemin before IH exposure. Eighteen male Sprague‐Dawley ( SD ) rats were randomized into three groups: control group, IH group ( PBS , ip) and IH + haemin group (haemin, 4 mg/kg, ip). The cardiac function was determined by echocardiography. Mitochondrial fission was evaluated by Mitotracker staining. The mitochondrial dynamics‐related proteins (mitochondrial fusion protein, Mfn2; mitochondrial fission protein, Drp1) were determined by Western blot. The apoptosis of cardiomyocytes and heart sections was examined by TUNEL . IH regulated mitochondrial dynamics‐related proteins (decreased Mfn2 and increased Drp1 expressions, respectively), thereby leading to mitochondrial fragmentation and cell apoptosis in cardiomyocytes in vitro and in vivo, while haemin‐induced HO ‐1 up‐regulation attenuated IH ‐induced mitochondrial fragmentation and cell apoptosis. Moreover, IH resulted in left ventricular hypertrophy and impaired contractile function in vivo, while haemin ameliorated IH ‐induced cardiac dysfunction. This study demonstrates that pharmacological activation of HO ‐1 pathway protects against IH ‐induced cardiac dysfunction and myocardial fibrosis through the inhibition of mitochondrial fission and cell apoptosis.