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 4

Lp(a) promotes inflammation in PMDMs and HCASMCs by inducing α7-nAChR-dependent activation of p38 MAPK signaling. (a) Representative western blot photo images showing the effect of treating patient monocyte-derived macrophages with 0.5 μM–2 μM Lp(a) for 60 min (upper panel) or with 1 μM Lp(a) at 15, 30, and 60 min time points (lower panel), on α7-nAChR, IL-6, p-p38 MAPK, and p38 MAPK protein expression levels. (b) Representative western blot photo images showing the effect of treating HCASMCs with 0.5 μM–2 μM Lp(a) for 60 min (upper panel) or with 1 μM Lp(a) at 15, 30, and 60 min time points (lower panel), on RhoA-GTP, RhoA, p-p38 MAPK, and p38 MAPK protein expression levels. (c) Representative western blot photo images showing that treating HCASMCs with 0.5 μM–2 μM Lp(a) for 60 min increases ROCK activity dose dependently. (d) Representative western blot images showing how shCHRNA7 affects the expression of RhoA-GTP, RhoA, α7-nAChR, p-p38 MAPK, and p38 MAPK in HCASMCs in the presence or absence of 1 μM Lp(a). Histograms show the effect of shCHRNA7 on CD80 MFI in HCASMCs in the presence or absence of 1 μM Lp(a). (e) PMDMs were treated with different concentrations of Lp(a) (0-2 μM) and the nitric oxide production was measured. (f) Lp(a) treatment dose dependently reduced the iNOS expression level in PMDMs. HCASMC: human coronary artery smooth muscle cell; MFI: median fluorescence intensity; PMDM: patient monocyte-derived macrophage; RhoA: Ras-homologous A; ROCK: Rho-kinase; shCHRNA7: α7-nAChR-targeting short hairpin RNA. , , and ; GAPDH served as loading control.

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