Activation of the monocytic alpha 7 nicotinic acetylcholine receptor modulates oxidative stress and inflammation-associated development of coronary artery spasm via a p38 MAP-kinase signaling-dependent pathway

作者：Hung, Ming-Yow; Wu, Yi-Hong; Bamodu, Oluwaseun Adebayo; Chen, Xi; Lin, Yen-Kuang; Hu, Patrick; Chang, Nen-Chung; Pang, Jong-Hwei Su^*; Yeh, Chi-Tai^*

来源：Free Radical Biology and Medicine, 2018, 120: 266-276.

DOI：10.1016/j.freeradbiomed.2018.03.050

• Coronary artery spasm
• Acute coronary syndrome
• Inflammation
• alpha 7-nAChR
• Nicotine acetylcholine receptor
• Monocytes
• Monocyte-derived macrophages
• p38-MAPK

Objective: Smoking and high-sensitivity C-reactive protein (hs-CRP) are risk factors for coronary artery spasm (CAS), which is characterized by the increased interleukin-6 (IL-6) level and monocyte counts; however, limited data are available regarding the role of cigarette-embedded nicotine in the modulation of monocytic inflammatory activity in CAS.
Approach: We investigated and elucidated the putative roles and associations of nicotine, monocytic IL-6, alpha 7 nicotinic acetylcholine receptor (alpha 7-nAChR), and CRP in CAS development.
Results: We demonstrated that a significantly increased alpha 7-nAChR (p=0.001) and IL-6 (p=0.0036) messenger RNA (mRNA) expression in the serum of patients with CAS. Serum hs-CRP levels exhibited a strong positive correlation with the monocytic mRNA expression of alpha 7-nAChR (r=0.71, p < 0.001) and IL-6 (r=0.49, p=0.006). The alpha 7-nAChR and IL-6 expression levels of the CAS group were also positively correlated (r=0.63, p < 0.001). Compared with the untreated controls, THP-1 cells and patient-derived monocytes treated with different concentrations of CRP displayed significantly increased expression levels of alpha 7-nAChR mRNA and protein (p=0.0054), in a dose-dependent manner. We also demonstrated that compared with the IL-6 expression elicited by CRP alone (p=0.0489), the CRP-induced rise in monocytic IL-6 mRNA and protein expression in the presence of nicotine (p=0.0002), is mediated by alpha 7-nAChR activation and the deregulation of the human p38 mitogen-activated protein kinases (MAPK) signaling pathway.
Conclusions: Our data demonstrate that the elevated monocytic IL-6 and alpha 7-nAChR mRNA and protein expression levels are associated with the interaction between nicotine and CRP positively modulates CAS development. Our study suggests the potential role of alpha 7-nAChR mRNA and/or protein expression as a diagnostic biomarker for CAS.

• 出版日期2018-5-20
• 单位长春大学; 浙江省人民医院