Sphingosine-1-phosphate-induced release of TIMP-2 from vascular smooth muscle cells inhibits angiogenesis

Journal of Cell Science
Keith S MascallGraeme F Nixon

Abstract

Following myocardial infarction, angiogenesis occurs as a result of thrombus formation, which permits reperfusion of damaged myocardium. Sphingosine 1-phosphate (S1P) is a naturally occurring lipid mediator released from platelets and is found in high concentrations at sites of thrombosis. S1P might therefore be involved in regulating angiogenesis following myocardial infarction and might influence reperfusion. The aims of this study were to determine the effects of S1P in human coronary arterial cell angiogenesis and delineate the subsequent mechanisms. An in vitro model of angiogenesis was developed using a co-culture of human coronary artery endothelial cells, human coronary smooth muscle cells and human fibroblasts. In this model, S1P inhibited angiogenesis and this was dependent on the presence of smooth muscle cells. The mechanism of the inhibitory effect was through S1P-induced release of a soluble mediator from smooth muscle cells. This mediator was identified as tissue inhibitor of metalloproteinase-2 (TIMP-2). Release of TIMP-2 was dependent on S1P-induced activation of Rho kinase and directly contributed to incomplete formation of endothelial cell adherens junctions. This was observed as a diffuse localisation of VE-...Continue Reading

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Citations

Jul 8, 2015·Proceedings of the National Academy of Sciences of the United States of America·Kelly M SchultzKristi S Anseth
Apr 29, 2014·Aquatic Toxicology·Catherine W McCollumMaria Bondesson
May 27, 2014·Biochemical and Biophysical Research Communications·Hyung Joon JooDo-Sun Lim
Jul 13, 2016·Biochemical Pharmacology·Christiane WirrigGraeme F Nixon
May 14, 2020·Environmental Toxicology·Sung-Lin HuChih-Hsin Tang
Nov 22, 2015·American Journal of Physiology. Heart and Circulatory Physiology·Fuyang ZhangLing Tao
Jul 25, 2021·International Journal of Molecular Sciences·Nerea Méndez-BarberoLuis Miguel Blanco-Colio

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