Platelets in Diabetes: The Role in the Hemostatic Regulation in Atherosclerosis

Abstract

Vascular diseases and related complications still represent the main cause of death in diabetic patients. Neuropathy, nephropathy, retinopathy, and disturbed nutritive tissue perfusion may result from reduced capillary microcirculation. These disturbances are diabetes specific. Macroangiopathy does not differ structurally from atherosclerotic lesions of nondiabetic subjects, but leads to accelerated cerebral, coronary, and peripheral artery disease. Occurrence of life-terminating thrombotic events, which are superimposed on those vascular lesions, are increased. Thus, morbidity and mortality of diabetics depend mainly on vascular complications. Normal blood flow is a prerequisite of adequate organ perfusion and results from vasomotion, plasma components, corpuscular blood elements, vascular architecture, and the undisturbed interaction of these components at the endothelial interface. Functional thromboresistance of the endothelial layer is reduced in the diabetic state. Increased intravascular thrombin generation, reduced fibrinolytic potential, and hyperactive platelets lead to a prethrombotic state. This thrombotic diathesis increases the permanent danger of acute flow interruption. Activated platelets operate by three mechanisms: (1) Microembolization of the capillaries; (2) local progression of preexisting vascular lesions by secretion of constrictive, mitogenic, and oxidative substances; (3) trigger of the prognosis-limiting arterial thrombotic event. We were able to show that the increased functional properties of diabetic platelets result from the primary release of larger platelets with enhanced thromboxane formation capacity and increased numbers of functional glycoprotein receptors GPIb and GPIIb/IIIa, which are synthesized in the megakaryocytes. The megakaryocyte-platelet system is turned on in diabetes mellitus. It could be demonstrated with the Duesseldorf III method of flow cytometric activation marker testing (CD62, CD63, thrombospondin) that predominantly large platelets circulate in an activated state in diabetes mellitus.(ABSTRACT TRUNCATED AT 250 WORDS)

Defects of the Heart, Eye, and Megakaryocytes in Peroxisome Proliferator Activator Receptor-binding Protein (PBP) Null Embryos Implicate GATA Family of Transcription Factors

“…Zinc finger protein GATA-1 is highly expressed in erythroid and megakaryocytic cells and is critical in the maturation of megakaryocytes, as precursor cells lacking GATA-1 exhibit a developmental arrest (21,59). Although megakaryocytes have not been implicated in the PPAR-signaling pathway, platelets are known to play an important role in the vascular complications associated with diabetes and atherosclerosis, two PPAR␥-related diseases (60). It seems likely that some of the hematopoietic abnormalities in PBP null embryos involve GATA factors; however, whether these abnormalities arise from an arrest in differentiation remains to be determined.…”

Activated platelets induce Weibel-Palade–body secretion and leukocyte rolling in vivo: role of P-selectin

“…Excessive platelet activation occurs in coronary bypass surgery and may result in thrombotic emboli and neurologic complications. 1 Furthermore, many inflammatory diseases including sepsis, 2,3 psoriasis, 4,5 diabetes, [6][7][8] and cystic fibrosis 9 are associated with circulating activated platelets. These pathologies are also associated with endothelial inflammation.…”

Platelet Degranulation Is Associated With Progression of Intima-Media Thickness of the Common Carotid Artery in Patients With Diabetes Mellitus Type 2

“…1,2 Diabetes has a number of effects on platelet function that may predispose to atherosclerosis. 3,4 These include increased primary and secondary platelet aggregation, 5,6 increased platelet activation with release of the contents of ␣-granules, 7,8 including ␤-thromboglobulin and platelet factor 4, and enhanced surface expression and activation of platelet glycoprotein IIb-IIIa (GPIIb-IIIa) complex. 9,10 Moreover, platelet NO synthase activity is reduced in diabetes.…”