Abstract

BACKGROUND: Obstructive sleep apnea (OSA) is associated with many cardiovascular disorders. Intermittent hypoxia (IH) is a key pathological hallmark of OSA. This study was conducted to evaluate the potential therapeutic effects and the associated mechanisms of adiponectin (APN) on IH induced human adult cardiac myocytes (HACMs) injury.

MATERIAL AND METHODS: HACMs were exposed to normoxia or IH (1% to 21% O₂) using a novel cell culture bio-reactor with gas-permeable membranes. Cell viability was detected by Cell Counting Kit-8 assay. Cell membrane integrity was assessed by the detection of lactate dehydrogenase (LDH) release. Cell apoptosis was analyzed by flow cytometry. Malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) levels were determined using specific assay kits. P-AMPK (AMP-activated protein kinase), p-LKB1, and p-p65 protein levels were measured by western blotting. Pro-inflammatory factors including interleukin (IL)-1β, IL-6, IL-8 expressions were detected by enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction.

RESULTS: The results showed that APN had no cytotoxic to HACMs. Compared with the control group, HACMs cell viability significantly decreased, LDH release increased and cell apoptosis increased in the IH group. The levels of IL-1β, IL-6, IL-8, MDA, and p-p65 were higher, while the levels of SOD, GSH-Px, p-AMPK, and p-LKB1 were lower in HACMs cells in the IH group than that in the control group. However, APN treatment significantly rescued these effects compared with the IH group in a dose-dependent manner.

CONCLUSIONS: In conclusion, these results indicated that APN protected against IH induced HACMs injury possibly mediated by AMPK and NF-κB pathway.

Keywords: Adiponectin, Apoptosis, Inflammation, Myocytes, Cardiac, Sleep apnea, obstructive, Adult, Blotting, Western, Cell Hypoxia, Glutathione Peroxidase, Heart Injuries, Interleukin-1beta, Interleukin-6, Interleukin-8, L-Lactate Dehydrogenase, Malondialdehyde, primary cell culture, Superoxide Dismutase