The Role of SPHK￣S1P Axis in Angiogenesis￣related Diseases / 中国生物化学与分子生物学报

ABSTRACT

Angiogenesis refers to the process of forming new blood vessels based on original blood vessels. Pathological angiogenesis is a sign of a series of diseases such as cancer, cardiovascular diseases, and retinopathy. Sphingosine 1-phosphate (S1P) is a signaling lipid synthesized by sphingosine kinase (SPHK) that exerts its diverse biological and pathophysiological roles through five G protein-coupled receptors (S1PR1-5) and initiates various signaling cascades by activating receptors that affect cell fate, vascular tension, endothelial function and integrity, and lymphocyte transport. The imbalance ofproduction and signal is closely related to pathological processes such as endothelial dysfunction and abnormal angiogenesis. Accumulating evidence suggests that the SPHK-S1P axis plays an important role in angiogenesis, especially in the development of tumors, diabetes retinopathy, atherosclerosis, myocardial infarction and other cardiovascular diseases. Studies on its roles and functions can provide new insights and drug therapeutic targets for the treatment of angiogenesis-related diseases. This review describes the molecular mechanisms by which the SPHK-S1P axis affects endothelial cell and smooth muscle cellproliferation, endothelial cell migration and the formation of lumen by endothelial cells, pericytes and smooth muscle cells through SPHK and S1PR1-5. The review also elaborates how the SPHK-S1P axis affects angiogenesis in tumors, cardiovascular diseases, diabetes and retinopathy through SPHK and S1PR1-5, and aims to provide new therapeutic strategy for related diseases by understanding the molecular mechanism of the SPHK-S1P axis in angiogenesis.