CaMKIIγ advances chronic intermittent hypoxia-induced cardiomyocyte apoptosis via HIF-1 signaling pathway.

Background: Our previous study have demonstrated chronic intermittent hypoxia (CIH) induced cardiomyocyte apoptosis and cardiac dysfunction. However, the molecular mechanisms are complicated and varied. In this study, we first investigated the CaMKIIγ expression and signaling pathway in the pathogenesis of cardiomyocyte apoptosis after CIH.

Methods: Rats were separated into CIH and Normoxia groups, and H9c2 cells were divided into Control and CIH + 8 h groups. Rat body weight (BW) was markedly gained from two to six weeks. Furthermore, CIH decreased cardiac dysfunction, damaged cellular structure, induced myocardial fibrosis, and promoted cardiomyocyte apoptosis by HE, masson, sirius-red, and TUNEL staining. Western blot, immunohistochemical, immunofluorescence, double immunofluorescence staining were performed to investigate CaMKIIγ, Bcl-2, Bax, Caspase 3, HIF-1 protein expression.

Results: Heart weight (HW) and HW/BW ratio in CIH group was markedly gained compared with the Normoxia group. CaMKIIγ expression was notably increased after CIH, and mainly expressed in the cytoplasm in vivo and vitro. The results of HIF-1 expression have the same trend of CaMKIIγ expression and cardiomyocyte apoptosis. In addition, the co-localizations of CaMKIIγ with Caspase 3, and CaMKIIγ with HIF-1 were observed by double immunofluorescence staining.

Conclusions: These results indicated increased CaMKIIγ expression advances CIH-induced cardiomyocyte apoptosis via HIF-1 signaling pathway, which afford a new insight and provide a potential therapy for OSA patients.