Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
Coronary artery spasm (CAS), an intense vasoconstriction of coronary arteries causing vessel occlusion, leads to myocardial ischemia and infarction. Smoking, age and high-sensitivity C-reactive protein (hs-CRP) are risk factors for CAS. In the mid 2000s, inflammation was shown to be associated with CAS, as evidenced by elevated peripheral white blood cell and monocyte counts, hs- CRP, and interleukin-6 (IL-6). In healthy people, rather than CRP, IL-6 is correlated with endothelial dysfunction, predisposing to CAS.
Recently, nicotinic acetylcholine receptors (nAChRs) have gained focus in cardiovascular studies because they mediate the effects of nicotine on the vasculature. Among nAChRs, α7-nAChRs (encoded by gene CHRNA7) are identified in inflammatory cells, such as monocytes and monocyte-derived macrophages, and constitute part of the immunomodulatory circuit termed as the cholinergic antiinflammatory pathway (CAP) upon stimulation. We present a novel evidence for the proinflammatory role of α7-nAChRs in human CAS, and demonstrate that the activation of monocytic α7-nAChRs might modulate the development of CAS.
Furthermore, in inflammatory response to oxidative stress, >85% of oxidizing phospholipids are present on Lipoprotein(a) (Lp[a]). We studied the role of human CHRNA7-p38MAPK inflammatory signaling pathway on Lp(a)- induced macrophage polarization and CAS development. Lp(a) significantly enhanced CHRNA7 expression in macrophages with increased inflammatory cytokine production and M1 surface marker, CD86. In CHRNA7-silenced macrophages, Lp(a)-induced pro-inflammatory cytokine production was remarkably decreased, and CD86 expression suppressed, while M2 marker CD206 expression was not. Collectively, these data suggest an essential role of CHRNA7- p38MAPK inflammatory signaling axis in macrophages in the pathogenesis of CAS.
 Que, X.; Hung, M.Y.; Yeang, C.; Gonen, A.; Prohaska, T.A.; Sun, X.; Diehl, C.; Määttä, A.; Gaddis, D.E.; Bowden, K.; Pattison, J.; MacDonald, J.G.; Ylä-Herttuala, S.; Mellon, P.L.; Hedrick, C.C.; Ley, K.; Miller, Y.I.; Glass, C.K.; Peterson, K.L.; Binder, C.J.; Tsimikas, S.; Witztum, J.L. Oxidized phospholipids are proinflammatory and proatherogenic in hypercholesterolaemic mice. Nature, 2018, 558(7709), 301-306.
 Hung, M.Y.; Wu, Y.H.; Bamodu, O.A.; Chen, X.; Lin, Y.K.; Hu, P.; Chang, N.C.; Pang, J.S.; Yeh, C.T. Activation of the Monocytic α7 Nicotinic Acetylcholine Receptor modulates oxidative stress and inflammation-associated development of CAS via a p38 MAP-Kinase signaling-dependent pathway. Free Radic. Biol. Med., 2018, 120, 266-276,
 Hung, M.Y.; Mao, C.T.; Hung, M.J.; Wang, J.K.; Lee, H.C.; Yeh, C.T.; Hu, P.; Chen, T.H.; Chang, N.C. CAS as related to anxiety and depression: A nationwide population-based study. Psychosom. Med., 2019, 81(3), 237-245.