P-selectin antagonism in inflammatory disease.
Inflammation plays a fundamental role in many chronic diseases, including atherosclerosis associated cardiovascular disease. Adhesion of immune cells plays a critical role in the inflammatory response and indeed the pathophysiology of inflammatory related diseases. P-selectin is an inflammatory adhesion molecule, enabling the recruitment of leukocytes to the endothelium and to activated platelets involved with the growing thrombus. P-selectin is critical in the progression of atherosclerosis as evidenced by knockout animal models where P-selectin knockout mice crossed with apoE deficient mice exhibit significantly reduced atherosclerosis and leukocyte recruitment in the plaque. A soluble form of P-selectin also exists, which may have pro-atherogenic and pro-thrombotic effects. Thus targeting of P-selectin remains a strong clinical candidate for developing novel therapeutic strategies in inflammatory diseases. This review will discuss the role of P-selectin and describe the function of P-selectin antagonists as clinical targets.
Baker IDI Heart and Diabetes Institute, Commercial Rd, Melbourne 3004, Australia. Kevin.woollard@bakeridi.edu.au
Kevin J
KJ
Woollard
Jaye
J
Chin-Dusting
D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D018450:Disease Progression; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D007962:Leukocytes / Q000276:immunology / Q000502:physiology; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D058990:Molecular Targeted Therapy; D019007:P-Selectin / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology*; D015539:Platelet Activation; D013927:Thrombosis / Q000276:immunology / Q000503:physiopathology
D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein