An engineered S1P chaperone attenuates hypertension and ischemic injury

作者：Steven Swendeman, Yuquan Xiong, Anna Cantalupo, Hui Yuan, Nathalie Burg, Yu Hisano, Andréane Cartier, Catherine H. Liu, Eric Engelbrecht, Victoria A. Blaho, Yi Zhang, K. Yanagida, Sylvain Galvani, Hideru Obinata, Jane E. Salmon, Teresa Sánchez, Annarita Di Lorenzo, Timothy Hla · 发表于：Science Signaling · 年份：2017 · DOI：10.1126/scisignal.aal2722 · 被引用次数：114 · 研究领域：Sphingolipid Metabolism and Signaling、Endoplasmic Reticulum Stress and Disease、Cholesterol and Lipid Metabolism

HDL), which carries the bioactive lipid sphingosine 1-phosphate (S1P), promotes endothelial function by activating G protein-coupled S1P receptors. Moreover, HDL-bound S1P is limiting in several inflammatory, metabolic, and vascular diseases. We report the development of a soluble carrier for S1P, ApoM-Fc, which activated S1P receptors in a sustained manner and promoted endothelial function. In contrast, ApoM-Fc did not modulate circulating lymphocyte numbers, suggesting that it specifically activated endothelial S1P receptors. ApoM-Fc administration reduced blood pressure in hypertensive mice, attenuated myocardial damage after ischemia/reperfusion injury, and reduced brain infarct volume in the middle cerebral artery occlusion model of stroke. Our proof-of-concept study suggests that selective and sustained targeting of endothelial S1P receptors by ApoM-Fc could be a viable therapeutic strategy in vascular diseases.