Abstract
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.
Highlights
Obstructive sleep apnoea (OSA) is characterized by recurrent episodes of airway collapse leading to intermittent hypoxia (IH) during nocturnal sleep
The protective effect of IH-induced haeme oxygenase-1 (HO-1) was not observed in heart tissue as we previously found that the compensated HO-1 up-regulation induced by IH was not sufficiently able to attenuate the cardiomyocyte apoptosis and cardiac injury in rats.[17]
We found that the IH treatment resembling a moderate OSA condition led to left ventricular cardiac hypertrophy and contractile dysfunction, and the functional compromise was accompanied by structural impairment, that is interstitial fibrosis
Summary
Obstructive sleep apnoea (OSA) is characterized by recurrent episodes of airway collapse leading to intermittent hypoxia (IH) during nocturnal sleep. Mitochondrial fission outweighs fusion and leads to cardiomyocyte apoptosis and subsequent heart failure.[13] It has not been determined whether IH induced cardiac injury via regulating mitochondrial dynamics, that is fusion and fission. It was reported that HO-1 overexpression protects doxorubicin-induced dilated cardiomyopathy via inhibiting Fis[1] and increasing Mfn1/Mfn[2] expression, suggesting that HO-1 plays a critical role in mediating mitochondrial dynamics to regulate heart function.[20]. Based on these findings, we have been suggested that IH could disturb mitochondrial dynamics via inducing mitochondrial fission, thereby leading to cardiomyocyte apoptosis and cardiac dysfunction. An HO-1 inducer, could attenuate IH-induced cardiac dysfunction through the inhibition of mitochondrial fragmentation and cardiomyocyte apoptosis
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
