Sphingosine-1-Phosphate Signaling in Endothelial Disorders.
Numerous preclinical studies indicate that sustained endothelial activation significantly contributes to tissue edema, perpetuates the inflammatory response, and exacerbates tissue injury ultimately resulting in organ failure. However, no specific therapies aimed at restoring endothelial function are available as yet. Sphingosine-1-phosphate (S1P) is emerging as a potent modulator of endothelial function and endothelial responses to injury. Recent studies indicate that S1PR are attractive targets to treat not only disorders of the arterial endothelium but also microvascular dysfunction caused by ischemic or inflammatory injury. In this article, we will review the current knowledge of the role of S1P and its receptors in endothelial function in health and disease, and we will discuss the therapeutic potential of targeting S1PR not only for disorders of the arterial endothelium but also the microvasculature. The therapeutic targeting of S1PR in the endothelium could help to bridge the gap between biomedical research in vascular biology and clinical practice.
Department of Pathology and Laboratory Medicine, Center for Vascular Biology, Weill Cornell Medical College, 1300 York Ave, Room A607B/Box 69, New York, NY, 10065, USA. tes2015@med.cornell.edu.
Teresa
T
Sanchez
D004730:Endothelium, Vascular / Q000503:physiopathology; D006801:Humans; D008246:Lysophospholipids / Q000502:physiology*; D055806:Microvessels / Q000503:physiopathology; D015398:Signal Transduction / Q000502:physiology*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000502:physiology; D014652:Vascular Diseases / Q000209:etiology* / Q000628:therapy*
D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D013110:Sphingosine
Atherosclerosis; Blood–brain barrier; Brain edema; Coronary artery disease; Hemorrhagic transformation; Immunosuppression; Malignant middle cerebral artery syndrome; Microcirculation; Microvascular dysfunction; Neurovascular injury; Non-reflow phenomenon; Stroke reperfusion therapies; Translational research; Vasogenic edema