Increased MCP-1 gene expression in monocytes of severe OSA patients and under intermittent hypoxia.
OBJECTIVE
Obstructive sleep apnea (OSA) is known to be a risk factor of coronary artery disease. Monocyte chemoattractant protein-1 (MCP-1), as a critical factor for monocyte infiltration, is known to play a role in the development of atherosclerosis. This study aimed to investigate the effect of intermittent hypoxia, the hallmark of OSA, on the MCP-1 expression of monocytes.


METHODS
Peripheral blood was sampled from 61 adults enrolled for suspected OSA. RNA was prepared from the isolated monocytes for the analysis of MCP-1. The effect of in vitro intermittent hypoxia on the regulation and function of MCP-1 was investigated on THP-1 monocytic cells and human monocytes. The mRNA and secreted protein levels were investigated by RT/real-time PCR and enzyme-linked immunosorbent assay, respectively.


RESULTS
Monocytic MCP-1 gene expression was found to be increased significantly in severe OSA patients. In vitro intermittent hypoxia was demonstrated to increase the mRNA and protein expression levels of MCP-1 dose- and time-dependently in THP-1 monocytic cells. The MCP-1 mRNA expression in monocytes isolated from OSA patient was induced to a much higher level compared to that from normal control. Pre-treatment with inhibitor for p42/44 MAPK or p38 MAPK suppressed the activation of MCP-1 expression by intermittent hypoxia.


CONCLUSIONS
This is the first study to demonstrate the increase of MCP-1 gene expression in monocytes of severe OSA patients. In addition, monocytic MCP-1 gene expression can be induced under intermittent hypoxia.
Graduate Institute of Clinical Medical Sciences, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan, Taiwan.|Sleep Center, Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan.
Li-Pang
LP
Chuang
Sleep Center, Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan.
Ning-Hung
NH
Chen
Graduate Institute of Clinical Medical Sciences, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan, Taiwan.
Yuling
Y
Lin
Graduate Institute of Clinical Medical Sciences, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan, Taiwan.
Wen-Shan
WS
Ko
Graduate Institute of Clinical Medical Sciences, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan, Taiwan. jonghwei@mail.cgu.edu.tw.
Jong-Hwei S
JH
Pang
D000328:Adult; D050197:Atherosclerosis / Q000175:diagnosis / Q000235:genetics; D018932:Chemokine CCL2 / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D000860:Hypoxia / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D017286:Polysomnography; D012333:RNA, Messenger / Q000235:genetics; D012016:Reference Values; D012307:Risk Factors; D020181:Sleep Apnea, Obstructive / Q000175:diagnosis / Q000235:genetics*
D018932:Chemokine CCL2; D012333:RNA, Messenger
Intermittent hypoxia; Monocyte; Monocyte chemoattractant protein-1; Obstructive sleep apnea