Singla Dinender K, Singla Reetu, Wang Jing
Division of Metabolic and Cardiovascular Sciences, Biomolecular Science Center, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, United States of America.
PLoS One. 2016 Jan 29;11(1):e0147897. doi: 10.1371/journal.pone.0147897. eCollection 2016.
Inflammation plays a fundamental role in the inception and development of atherosclerosis (ATH). Mechanisms of inflammation include the infiltration of monocytes into the injured area and subsequent differentiation into either pro-inflammatory M1 macrophages or anti-inflammatory M2 macrophages. We have previously published data suggesting bone morphogenetic protein-7 (BMP-7) enhances M2 macrophage differentiation and anti-inflammatory cytokine secretion in vitro. In this regard, we hypothesized BMP-7 would inhibit plaque formation in an animal model of ATH through monocytic plasticity mediation. ATH was generated in male and female Apo E(-/-) mice via partial left carotid artery (PLCA) ligation and mice were divided into 3 groups: Sham, PLCA, and PLCA+BMP-7 (200 ug/kg; i.v.). Our data suggest that BMP-7 inhibits plaque formation and increases arterial systolic velocity. Furthermore, we report inhibition of monocyte infiltration and a decrease in associated pro-inflammatory cytokines (MCP-1, TNF-α, and IL-6) in the PLCA+BMP-7 mice. In contrast, our data suggest a significant (p<0.05) increase in M2 macrophage populations with consequential enhanced anti-inflammatory cytokine (IL-1RA, IL-10, and Arginase 1) expression following BMP-7 treatment. We have also observed that mechanisms promoting monocyte into M2 macrophage differentiation by BMP-7 involve the upregulation and activation of the BMP-7 receptor (BMP-7RII). In conclusion, we report that BMP-7 has the potential to mediate cellular plasticity and mitigate the inflammatory immune response, which results in decreased plaque formation and improved blood velocity.
炎症在动脉粥样硬化（ATH）的发生和发展中起重要作用。炎症机制包括单核细胞浸润到损伤区域并随后分化为促炎性M1巨噬细胞或抗炎性M2巨噬细胞。我们之前发表的数据表明骨形态发生蛋白-7（BMP-7）在体外可增强M2巨噬细胞分化和抗炎细胞因子分泌。在这方面，我们假设BMP-7会通过单核细胞可塑性介导抑制ATH动物模型中的斑块形成。通过部分左颈动脉（PLCA）结扎在雄性和雌性Apo E（-/-）小鼠中诱导产生ATH，并将小鼠分为3组：假手术组、PLCA组和PLCA + BMP-7组（200μg / kg；静脉注射）。我们的数据表明BMP-7可抑制斑块形成并增加动脉收缩期速度。此外，我们报告PLCA + BMP-7组小鼠中单核细胞浸润受到抑制且相关促炎细胞因子（MCP-1、TNF-α和IL-6）减少。相比之下，我们的数据表明BMP-7治疗后M2巨噬细胞群体显著增加（p<0.05），随之抗炎细胞因子（IL-1RA、IL-10和精氨酸酶1）表达增强。我们还观察到BMP-7促进单核细胞向M2巨噬细胞分化的机制涉及BMP-7受体（BMP-7RII）的上调和激活。总之，我们报告BMP-7有潜力介导细胞可塑性并减轻炎症免疫反应，从而减少斑块形成并改善血流速度。
