Heparanase expression upregulates platelet adhesion activity and thrombogenicity.
Heparanase is an endo-glucuronidase that specifically cleaves heparan sulfate (HS) and heparin polysaccharides. The enzyme is expressed at low levels in normal tissues, but is often upregulated under pathological conditions such as cancer and inflammation. Normal human platelets express exceptionally high levels of heparanase, but the functional consequences of this feature remain unknown. We investigated functional roles of heparanase by comparing the properties of platelets expressing high (Hpa-tg) or low (Ctr) levels of heparanase. Upon activation, Hpa-tg platelets exhibited a much stronger adhesion activity as compared to Ctr platelets, likely contributing to a higher thrombotic activity in a carotid thrombosis model. Furthermore, we found concomitant upregulated expression of both heparanase and CD62P (P-selectin) upon activation of mouse and human platelets. As platelets play important roles in tumor metastasis, these findings indicate contribution of the platelet heparanase to hyper-thrombotic conditions often seen in patients with metastatic cancer.
['Cui|Hao|H|', 'Tan|Ying-Xia|YX|', 'Österholm|Cecilia|C|', 'Zhang|Xiao|X|', 'Hedin|Ulf|U|', 'Vlodavsky|Israel|I|', 'Li|Jin-Ping|JP|']
D000818:Animals D001792:Blood Platelets D002339:Carotid Arteries D002469:Cell Separation D002712:Chlorides D003433:Crosses, Genetic D004912:Erythrocytes D005260:Female D005290:Ferric Compounds D005434:Flow Cytometry D005786:Gene Expression Regulation D005966:Glucuronidase D006025:Glycosaminoglycans D006497:Heparitin Sulfate D006801:Humans D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D008822:Mice, Transgenic D019007:P-Selectin D015539:Platelet Activation D010973:Platelet Adhesiveness D051149:Selenoprotein P D013927:Thrombosis D015854:Up-Regulation
heparanase platelet platelet adhesion heparan sulfate thrombosis