Expression of Adhesion Molecules on the Surface of Activated Platelets is Diminished by PGI(2)-analogues and an NO (EDRF)-Donor: A Comparison Between Platelets of Healthy and Diabetic Subjects
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Adhesion molecules such as P-selectin (CD 62), glycoprotein (CP) 53 (CD63) and thrombospondin play a decisive role in the thrombogenic transformation of platelets. Here we present evidence obtained using flow cytometric analysis that the PGI(2)-mimetics iloprost and taprostene, and an NO (EDRF)donor (SIN-1) are able to inhibit the expression of P-selectin, GP 53 and thrombospondin on human platelets activated by submaximal concentrations of thrombin. Since the half-maximal concentrations for inhibition of antigen expression (0.15 nM for iloprost, 3.0-5.3 nM for taprostene) are much lower than for activation of adenylate cyclase (1.4 nM for iloprost and 29.4 nM for taprostene) our data suggest that the occupation of a small number of PGI(2)-receptors is sufficient to inhibit the thrombogenic transformation and that spare PGI(2)-receptors are present on human platelets. In diabetes, the EC(50) for inhibition of expression of platelet antigens is shifted to higher concentrations suggesting that platelets from type 1 diabetic patients are partly resistant to PGI(2). Since the dose dependent increase in c-AMP by iloprost is not changed and intraplatelet c-AMP is elevated in platelets of diabetic patients, we assume that steps in the activation cascade subsequent to activation of adenylate cyclase are disturbed in diabetes.
Kreutz R, Nystrom P, Kreutz Y, Miao J, Kovacs R, Desta Z Platelets. 2012; 24(2):145-50.
PMID: 22385219 PMC: 4028123. DOI: 10.3109/09537104.2012.661107.
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Fleming I, Bauersachs J, Busse R Mol Cell Biochem. 1996; 157(1-2):137-45.
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