Apolipoprotein (a)/Lipoprotein(a)-Induced Oxidative-Inflammatory α7-nAChR/p38 MAPK/IL-6/RhoA-GTP Signaling Axis and M1 Macrophage Polarization Modulate Inflammation-Associated Development of Coronary Artery Spasm

Figure 2

The apolipoprotein (a) component of Lp(a) interacts with and induces α7-nAChR expression in the monocyte-derived macrophages of patients with CAS. Graphical representation of the effect of 500 nM LDL or Lp(a) on the (a) relative expression of CHRNA7 mRNA or (b) relative luciferase reporter activity of α7-nAChR in the patient monocyte-derived macrophages. Histograms showing the effect of 100 nM–1000 nM Lp(a) on the (c) relative expression of CHRNA7 mRNA or (d) relative luciferase reporter activity of α7-nAChR in the patient monocyte-derived macrophages. (e) Methyllycaconitine (MLA) dose dependently inhibited the Lp(a)-induced activation of α7-nAChR. (f) Visualization of the direct molecular interaction between Lp(a) and α7-nAChR using the PyMoL molecular docking and visualization software. Complex formation criteria are indicated. (g) Immunofluorescence demonstrated induced expression of α7-nAChR after Lp(a) treatment and fluorescent-protein tagging showed a high correlation for protein localization with α-BTX. Original magnification ×200. DAPI (blue) served as a nuclear marker. , , and . Lp(a): lipoprotein(a); CHRNA7: gene encoding α7-nAChR.

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