Zhao Jiawei, Garcia Dante, Gartung Allison, Lee Menq-Jer
Department of Pathology, Cardiovascular Research Institute, Karmanos Cancer Institute, Wayne State University School of Medicine, 540 East Canfield Ave., Scott Hall 9215, Detroit, MI, 48201, USA,
Curr Atheroscler Rep. 2015 May;17(5):504. doi: 10.1007/s11883-015-0504-y.
Endothelial inflammation is an important risk factor in the initiation and development of vascular disease. Therefore, signaling cascades and patho-physiological outcomes of endothelial inflammation are important questions in vascular biology. Recent studies suggest that sphingosine-1-phosphate receptor subtype 2 (S1PR2) signaling in endothelial cells (ECs) play a critical role in endothelial inflammation. For example, ECs present in atherosclerotic plaques exhibit senescence phenotype. Levels of S1PR2 are markedly increased in cultured senescent ECs and in lesion regions of atherosclerotic endothelium. Also, inflammatory cytokines and mechanical flow stress profoundly increase S1PR2 levels in ECs. Inhibition of endothelial S1PR2 signaling diminishes endothelial senescence-associated functional impairments and atherogenic stimuli-induced endothelial activation. In contrast, activation of endothelial S1PR2 stimulates the production of pro-inflammatory chemokines/cytokines and lipid mediators in ECs. In this article, we will review signaling and functions of sphingosine-1-phosphate (S1P) receptors in endothelial biology, with particular focus on endothelial S1PR2 signaling-mediated endothelial inflammation.
内皮炎症是血管疾病发生和发展的重要危险因素。因此，内皮炎症的信号级联反应和病理生理结果是血管生物学中的重要问题。最近的研究表明，内皮细胞（ECs）中的1-磷酸鞘氨醇受体2型（S1PR2）信号在内皮炎症中起关键作用。例如，存在于动脉粥样硬化斑块中的内皮细胞表现出衰老表型。在培养的衰老内皮细胞和动脉粥样硬化内皮的病变区域中，S1PR2的水平显著升高。此外，炎性细胞因子和机械血流应力可显著提高内皮细胞中S1PR2的水平。抑制内皮S1PR2信号可减少内皮衰老相关的功能障碍以及动脉粥样硬化刺激诱导的内皮激活。相反，激活内皮S1PR2可刺激内皮细胞中促炎性趋化因子/细胞因子和脂质介质的产生。在本文中，我们将综述1-磷酸鞘氨醇（S1P）受体在内皮生物学中的信号传导和功能，特别关注内皮S1PR2信号介导的内皮炎症。
