Monocyte/macrophage β2-AR as a target of antisympathetic excitation-induced atherosclerotic progression

Abstract

ABSTRACT. The aim of this study was to determine whether monocyte/macrophage β2-AR could act as the therapeutic target of antisympathetic excitation-induced atherosclerotic progression. Cultivated human THP-1 cells were divided into different groups and incubated with isoprenaline, metoprolol, propranolol or β2-AR blocker for 24 h, together with oxidized low-density lipoprotein (ox-LDL). Afterwards, each group was analyzed for C-C chemokine receptor type 2 (CCR2) expression, monocyte chemotactic protein 1 (MCP-1) release into medium and cell migration ability. In the isoprenaline group, CCR2 protein level was increased, as well as the secretion of MCP-1, and cell motility was enhanced, in a concentration-dependent manner. Propranolol and ICI 118,551 significantly reversed the stimulatory effect of isoprenaline on THP-1 cells induced by ox-LDL, but only high concentrations of metoprolol interfered significantly with the action of isoprenaline (P < 0.05). Isoprenaline or a β-AR blocker could mediate through β2-AR, affecting MCP-1 secretion, CCR2 protein expression and cell migration capacity of THP-1 cells. Therefore, monocytemacrophage β2-AR may act as a target of antisympathetic excitation- Monocyte-macrophage β2-AR induced atherosclerotic progression.

Propranolol Promotes Monocyte-to-Macrophage Differentiation and Enhances Macrophage Anti-Inflammatory and Antioxidant Activities by NRF2 Activation

“…Here, we showed that propranolol downregulated HLA-DR in M1 conditions, an event that supports the M2-like profile generated by the β-AR signaling antagonism. Our results on the ability of propranolol to affect the M1 pro-inflammatory phenotype are consistent with finding by Guo et al, who found that propranolol inhibits the pro-inflammatory MCP-1 and CCR2 protein expression of macrophages [37].…”

β2-Adrenergic receptor-dependent chemokine receptor 2 expression regulates leukocyte recruitment to the heart following acute injury

“…These differences may be due to the lack of specificity of norepinephrine and epinephrine treatment and activation of multiple adrenergic receptor subtypes. Further, β2AR stimulation was previously shown in THP-1 human monocytic cells to increase CCR2 expression and migration through an undefined mechanism (30), whereas another study demonstrated that treatment of THP-1 cells with cAMP-elevating agents, including PDE3 inhibitors and dibutyryl cAMP, decreased both CCR2 expression and CCL2-mediated migration (31). These results may suggest that Gα s protein-dependent β2AR signaling acts to repress CCR2 expression.…”

Oxidized low-density lipoprotein induces M2-type differentiation of macrophages to promote the protracted progression of atherosclerotic inflammation in high-fat diet-fed ApoE -/- mice

“…Therefore, reducing the number of M2-type macrophages in plaques or the degree of M2-type polarization and preventing nonapoptotic death (such AS focal death) including cell membrane rupture induced by excessive lipid phagocytosis of M2-type macrophages may be the important mechanism of the above-mentioned β-AR blocker inhibiting the progression of AS. Previous studies (42) and other studies (40)(41)(42) of this research group showed that β-AR blockers with different degrees of blocking effect on β2-AR: including metoprolol (43,44), propranolol (44)(45)(46), carvedilol (47) and nebivolol (48,49) had significant anti-AS effects. Therefore, reducing the number of M2-type macrophages in plaques or the degree of M2-type polarization and preventing non-apoptotic death (such AS pyroptosis) including cell membrane rupture induced by excessive lipid phagocytosis of M2-type macrophages may be the important mechanism of the above-mentioned β-AR blocker inhibiting the progression of AS.…”