Close Relationship between the Platelet Activation Marker CD62 and the Granular Release of Platelet-Derived Growth Factor

Abstract

The expression of CD62 on the surface of platelets is considered to be an indicator of platelet degranulation and secretion. We characterized the relationship between CD62 expression and platelet-derived growth factor (PDGF) AB and PDGF BB secretion in response to thrombin-receptor activating peptide (TRAP). The principal findings were 1) expression of CD62 as a constituent of platelet ␣-granule membrane and secretion of PDGF, an important ingredient of ␣-granules, can be stimulated by TRAP-induced activation in a dose-dependent fashion; 2) the activation marker and secretion product are closely correlated with each other; and 3) changes in the CD62 expression induced by a drug, namely clopidogrel, or by a disease, namely diabetes, are paralleled by changes in PDGF secretion. Although CD62 is perceived as an activation marker of platelets indicating enhanced aggregability and secretion of ␣-granular content, the proof that the CD62 status and its modifications reflect directly the actual secretion of the most important platelet mitogen, PDGF, has so far not been given. This ex vivo-in vitro study shows that at least for the activation pathway provided by the PAR-1 receptor for which TRAP is the selective agonist, CD62 expression on platelets could be a surrogate for their secretory activity.

A Decline in Platelet Activation and Inflammatory Cell Infiltration is Associated with the Phenotypic Redifferentiation of Neointimal Smooth Muscle Cells after Bare-metal Stent Implantation in Acute Coronary Syndrome

“…The present study of ACS patients clearly demonstrated that at the earliest stage after BMS, PDGF is expressed in P-selectin-positive activated platelets. This finding is in agreement with previous studies, which revealed a close relationship between platelet activation and release of PDGF 34) . Our observations in lesions with neointimal proliferation after BMS further showed that the expression of PDGF-B and PDGF-receptor in the neointima decreased markedly in the later stage, 6 months after BMS; at this stage, neointimal SMCs differentiated into a highly differentiated state.…”

Reduced Vascular NO Bioavailability in Diabetes Increases Platelet Activation In Vivo

“…46 In platelets from diabetic patients, agonist-induced release of plateletderived growth factor is enhanced. 47 Even in metabolically stable, islet cell antibody-positive individuals, platelet activation markers (CD62, CD63, thrombospondin) were significantly increased. 48 The impact of activated platelets on morbidity and mortality in diabetes is extremely relevant because enhanced platelet activation is an initial step in atherosclerosis and responsible for lesion progression, 49 and excessive cardiovascular complications are associated with diabetes.…”

Prognostic Impact of Microvasculopathy on Survival After Heart Transplantation

“…Enhanced platelet activation has been described in the development and progression of epicardial vasculopathy 27 and might be involved in our finding of lower risk for microvasculopathy in patients on assist device before transplantation, who are usually on antiplatelet therapy. Clopidogrel is known to have antithrombotic and antagonistic effects on smooth muscle cell proliferation, 28 and we suggest that it may be a novel approach in prevention and treatment of transplant vasculopathy in epicardial and small intramyocardial blood vessels. Our study also supports a known prophylactic approach to transplant vasculopathy, which is the use of statins.…”