Shear-Induced Platelet Adhesion and Aggregation on Subendothelium Are Increased in Diabetic Patients

Knobler, Hilla; Savion, Naphtali; Шенкман, Борис; Kotev-Emeth, Shlomo; Varon, David

doi:10.1016/s0049-3848(98)00050-4

Cited by 93 publications

(54 citation statements)

References 36 publications

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“…42 Furthermore, patients with diabetes exhibit an enhanced adhesion and aggregation of platelets on extracellular matrix. 43 Patients with exaggerated platelet aggregation have an increased risk for restenosis after percutaneous transluminal coronary angioplasty. 44 Prolonged hyperglycemia induces abnormal Ca 2ϩ homeostasis similar to changes observed in platelets from diabetic patients.…”

Section: Discussionmentioning

confidence: 99%

Reduced Vascular NO Bioavailability in Diabetes Increases Platelet Activation In Vivo

Schäfer

Nicholas

Cai

et al. 2004

ATVB

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Objective-Platelet activation is a feature of cardiovascular disease that is also characterized by endothelial dysfunction.The direct relationship between impaired endothelium-derived NO bioavailability and platelet activation remains unclear. We investigated whether acute inhibition of NO production modulates platelet activation in mice and whether specific rescue of endothelial function in diabetes modifies platelet activation. Methods and Results-Intravenous injection of the NO synthase inhibitor N G -nitro-L-arginine methyl ester in wild-type (WT) mice significantly reduced platelet vasodilator-stimulated phosphoprotein (VASP) phosphorylation and increased platelet surface expression of P-selectin, CD40 ligand, and fibrinogen platelet binding, demonstrating that NO production exerts tonic inhibition of platelet activation in mice. Diabetes was induced by streptozotocin injection in WT or endothelial-targeted guanosine 5Ј-triphosphate cyclohydrolase I (GCH)-transgenic (GCH-Tg) mice protected from endothelial dysfunction in diabetes by sustained levels of tetrahydrobiopterin in vascular endothelium. Platelet VASP phosphorylation was significantly reduced in diabetic WT but not in diabetic GCH-Tg mice. P-selectin, CD40 ligand expression, and fibrinogen binding were increased in diabetic WT mice but remained unchanged compared with controls in endothelial-targeted GCH-Tg mice. Key Words: diabetes Ⅲ endothelial nitric oxide synthase Ⅲ platelets Ⅲ endothelial dysfunction T he endothelium plays a crucial role in control of vascular tone by releasing endothelium-derived autocoids, the most important of which is NO, 1 generated by endothelial NO synthase (eNOS). NO also inhibits platelet activation, adhesion and aggregation; reduced NO bioactivity is associated with arterial thrombosis in animal models and in individuals with endothelial dysfunction. 2 The importance of NO in platelet function was shown by in vitro experiments such as inhibition of platelet aggregation by endothelial cells 3 or NO donors. 4,5 NO formation inhibition causes platelet activation, 6 and exogenous NO can even reverse agonist-induced activation of platelet glycoprotein (GP) IIb/IIIa. 7 The finding that platelets adhere to dysfunctional endothelium and that expression of potential adhesion molecules is enhanced under these conditions suggests that NO may modulate platelet activation in vascular disease states. 8 We demonstrated recently that inhibition of systemic NO formation in healthy humans rapidly induces platelet activation, an effect that could be reversed by exogenous NO. 6 Indeed, increased platelet activation is observed in diseases characterized by chronic endothelial dysfunction such as acute coronary syndromes, 9 congestive heart failure, 10,11 diabetes, 12,13 and hypercholesterolemia. 14 In patients with advanced atherosclerosis, impaired endotheliumdependent release of NO leads to reduced platelet cGMP formation. 15 It remains uncertain whether endothelial-derived NO has a more important role in tonic suppression of platelet ...

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Section: Discussionmentioning

confidence: 99%

Reduced Vascular NO Bioavailability in Diabetes Increases Platelet Activation In Vivo

Schäfer

Nicholas

Cai

et al. 2004

ATVB

View full text Add to dashboard Cite

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“…Platelets from diabetic patients demonstrate abnormal aggregation and enhanced shear-induced adhesion (35). These functional abnormalities of the platelet in diabetic patients have been linked to increased levels of cell surface adhesion molecules, including the GP IIb/IIIa receptor (36).…”

Section: Discussionmentioning

confidence: 99%

Effect of Diabetes on Long-Term Mortality Following Contemporary Percutaneous Coronary Intervention

et al. 2004

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OBJECTIVE -Diabetic patients are known to have reduced long-term survival following percutaneous transluminal coronary angioplasty compared with nondiabetic patients. However, it is unknown whether this survival disadvantage has persisted in the era of contemporary percutaneous coronary intervention (PCI) techniques, which include the widespread use of stents and the availability of platelet glycoprotein (GP) IIb/IIIa inhibitors. RESEARCH DESIGN AND METHODS -Three hospitals in New YorkCity contributed prospectively defined data on 4,284 patients undergoing PCI. The primary end point was all-cause mortality following hospital discharge for PCI.RESULTS -Hypertension, renal insufficiency, and renal failure requiring dialysis were all more common in diabetic patients, whereas active smoking was less frequent. Congestive heart failure on admission was more common in diabetic than nondiabetic patients (7.7 vs. 4.0%, P Ͻ 0.001). Stents were placed in 78% of nondiabetic patients and 75% of diabetic patients (P ϭ 0.045). Platelet GP IIb/IIIa antagonists were administered to 23% of nondiabetic and 24% of diabetic patients (P ϭ NS). At a mean follow-up of 3 years, mortality was 8% among nondiabetic patients and 13% for diabetic patients (P Ͻ 0.001). After adjustment for differences in baseline characteristics between nondiabetic and diabetic patients, diabetes remained a significant independent hazard for late mortality (hazard ratio 1.462, 95% CI 1.169 -1.828; P ϭ 0.001).CONCLUSIONS -Following contemporary PCI, diabetic patients continue to have worse survival than nondiabetic patients.

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“…Уже известно, что тромбоциты больных СД гиперак-тивные [56], и антиагрегантная терапия часто снижает риск сердечно-сосудистых осложнений у таких боль-ных [57]. При ГСД материнская гипергликемия связана с компенсаторной гиперинсулинемией плода, которая приводит к фетальным и неонатальным осложнениям.…”

Section: репродуктивное здоровьеunclassified

Hormonal, electrolyte disturbances and features of hemostasis in term newborn infants of mothers with gestational diabetes mellitus.

et al. 2015

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естационный сахарный диабет (ГСД) -гипер-гликемия, возникшая или впервые выявленная во время беременности, причем не исключается возможность того, что нарушение углеводного обмена могло предшествовать беременности, но оно не было уста-новлено. Распространенность ГСД может варьировать от 1 до 14% (в среднем 7%), что зависит от анализируемой популяции женщин и частоты применения перораль-ного глюкозотолерантного теста (ПГТТ), применяемого для диагностики заболевания [1]. Данное определение ГСД в Российской Федерации существовало до 2012 г., после анализа результатов крупного наблюдательного исследо-вания HAPO подходы к диагностике и определению ГСД во многих странах, в том числе и в России, изменились.Исследование

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Shear-Induced Platelet Adhesion and Aggregation on Subendothelium Are Increased in Diabetic Patients

Cited by 93 publications

References 36 publications

Reduced Vascular NO Bioavailability in Diabetes Increases Platelet Activation In Vivo

Reduced Vascular NO Bioavailability in Diabetes Increases Platelet Activation In Vivo

Effect of Diabetes on Long-Term Mortality Following Contemporary Percutaneous Coronary Intervention

Hormonal, electrolyte disturbances and features of hemostasis in term newborn infants of mothers with gestational diabetes mellitus.

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