{"title":"Targeting the P-selectin/PSGL-1 pathway: discovery of disease-modifying therapeutics for disorders of thromboinflammation","authors":"Samira Escopy , Elliot L. Chaikof","doi":"10.1016/j.bvth.2024.100015","DOIUrl":null,"url":null,"abstract":"<div><h3>Abstract</h3><p>P-selectin is a membrane glycoprotein and a member of the selectin family of cell adhesion molecules. It is prestored in α-granules of platelets and Weibel-Palade bodies of endothelial cells and is rapidly expressed on their surfaces upon activation during the course of an inflammatory response. Although a critical component of the innate immune system, the interaction of P-selectin with its cognate ligand, P-selectin glycoprotein ligand 1 (PSGL-1) may mediate maladaptive events central to the pathophysiology of venous thromboembolism, cardiovascular disease, stroke, metabolic syndrome, and sickle cell disease, among other disorders. As a consequence, a growing understanding of the significance of P-selectin and PSGL-1 in human disease has motivated the design of inhibitors that target the P-selectin/PSGL-1 pathway. Herein, we review the development and evaluation of both biologic and small-molecule inhibitors, including preclinical studies and clinical trials that have evaluated therapeutic potential of these agents for a variety of diseases linked to dysregulated inflammatory and thrombotic responses.</p></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"1 3","pages":"Article 100015"},"PeriodicalIF":0.0000,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950327224000159/pdfft?md5=62bf22670a3a660320054f729ff7f483&pid=1-s2.0-S2950327224000159-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Blood Vessels, Thrombosis & Hemostasis","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2950327224000159","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
P-selectin is a membrane glycoprotein and a member of the selectin family of cell adhesion molecules. It is prestored in α-granules of platelets and Weibel-Palade bodies of endothelial cells and is rapidly expressed on their surfaces upon activation during the course of an inflammatory response. Although a critical component of the innate immune system, the interaction of P-selectin with its cognate ligand, P-selectin glycoprotein ligand 1 (PSGL-1) may mediate maladaptive events central to the pathophysiology of venous thromboembolism, cardiovascular disease, stroke, metabolic syndrome, and sickle cell disease, among other disorders. As a consequence, a growing understanding of the significance of P-selectin and PSGL-1 in human disease has motivated the design of inhibitors that target the P-selectin/PSGL-1 pathway. Herein, we review the development and evaluation of both biologic and small-molecule inhibitors, including preclinical studies and clinical trials that have evaluated therapeutic potential of these agents for a variety of diseases linked to dysregulated inflammatory and thrombotic responses.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
