Dopamine D1-Like Receptors Suppress the Proliferation of Macrophages Induced by Ox-LDL

Background/Aims: Oxidized low-density lipoprotein (Ox-LDL) induces macrophage proliferation, a key physiological process which leads to atherosclerosis. The aim of this study was to determine the effects of dopamine D-1-like receptors on macrophage proliferation induced by Ox-LDL. Methods: The expression of dopamine D-1-like receptors was determined by immunohistochemistry, reverse transcriptase-polymerase chain reaction (RT-PCR) and immunoblotting. The effect of D-1-like receptors on macrophage proliferation induced by OxLDL was measured by (3)[H]-thymidine incorporation and cell number count. Results: Dopamine D-1-like receptors were present in macrophages as determined by immunohistochemistry, RTPCR and immunoblotting. A D-1-like receptor agonist, fenoldopam, which by itself had no effect on macrophage proliferation, inhibited the stimulatory effect of Ox-LDL on macrophage proliferation. This was further confirmed by the D1-like receptor antagonist SCH 23390 blocking the effect of fenoldopam, thereby indicating that the fenoldopam action was receptor specific. Phosphatidylinositol 3-kinase (PI3K/Akt) and mitogen-activated protein kinase (MAPK/ERK) pathways were also involved in the proliferative effect of Ox-LDL because in the presence of PI3K/Akt or MAPK/ERK inhibitors, LY294002 or PD98059, the stimulatory effects of Ox-LDL were blocked. Moreover, the stimulatory effect of Ox-LDL on the phosphorylation of ERK and Akt was significantly reduced by fenoldopam in macrophages. Additional experiments found that both D-1 and D-5 receptor expression was lower in the peritoneal macrophages from Apolipoprotein E-deficient mice compared to the control C57Bl/6J mice. Conclusions: Macrophages express D-1-like receptors. The activation of the D-1-like receptors significantly inhibits Ox-LDL-induced macrophage proliferation, possibly through the inhibition of the PI3K/Akt and MAPK/ERK signaling pathways. Copyright (C) 2016 S. Karger AG, Basel