Monocytic C-C chemokine receptor 5 expression increases in in vitro intermittent hypoxia condition and in severe obstructive sleep apnea patients

Li-Pang Chuang,Cheng-Ta Yang,Chung-Chi Huang,Jong-Hwei S Pang,Shih-Wei Lin,Li-Fu Li,Kuo-Chin Kao,Ning-Hung Chen,Han-Chung Hu

doi:10.1007/s11325-019-01797-4

Li-Pang Chuang, Cheng-Ta Yang + Show 7 more

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https://doi.org/10.1007/s11325-019-01797-4

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Abstract

PurposeObstructive sleep apnea (OSA) patients have higher risk of cardiovascular disease. C-C chemokine receptor 5 (CCR5), as an important receptor for monocyte recruitment and the initiation of atherosclerosis, was studied under intermittent hypoxia and in OSA patients.MethodsThe expression and function of CCR5 regulated by intermittent hypoxia in monocytic THP-1 cells were investigated in an in vitro intermittent hypoxia culture system. The expression levels of protein and mRNA were analyzed by western blot and RT/real-time PCR analysis. Cell adhesion assay and transwell filter migration assay were carried out to investigate the adhesion and chemotaxis of monocytes. In addition, the mRNA expression of CCR5 in monocytes isolated from peripheral blood of 72 adults was analyzed.ResultsIntermittent hypoxia upregulated the expression of CCR5 in THP-1 cells and enhanced the adhesion and chemotaxis of monocytes to vascular endothelial cells mediated by RANTES. The CCR5 expression induced by intermittent hypoxia was inhibited by inhibitor for p42/44 MAPK. Besides, the expression of CCR5 in monocytes increased along the AHI value especially in severe OSA patients that was statistically significant compared with mild and moderate OSA groups.ConclusionsThis study demonstrated the increased monocytic CCR5 gene expression in patients with severe OSA. Intermittent hypoxia, the characteristic of OSA, induced monocytic CCR5 gene expression and the enhanced RANTES-mediated chemotaxis and adhesion through p42/44 MAPK signal pathways.

Highlights

Obstructive sleep apnea (OSA), which affects more than 5% of the adult population, is an increasing prevalent disease [1]
Intermittent hypoxia upregulated the expression of chemokine receptor 5 (CCR5) in THP-1 cells and enhanced the adhesion and chemotaxis of monocytes to vascular endothelial cells mediated by RANTES
The result obtained by western blot analysis further demonstrated that the membrane CCR5 proteins isolated from THP-1 cells were significantly amplified by intermittent hypoxia (Fig. 1b)

Summary

Introduction

Obstructive sleep apnea (OSA), which affects more than 5% of the adult population, is an increasing prevalent disease [1]. It is characterized by repetitive episodes of complete or partial. Among these cardiovascular diseases, coronary heart disease is the result of the accumulation of atheromatous plaques within the coronary artery walls [5]. The activation of leukocyte and endothelial cell and the adhesion of leukocyte to endothelium are known to result in the inflammation and the development of atherosclerosis [9]. The transmigration of circulating monocytes into vascular intimal space initially attracted by various chemokines secreted by vascular endothelial cells is an important tread in the progression of atherosclerosis [10]

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