Modulators of intraplatelet calcium concentration affect the binding of thrombospondin to blood platelets in healthy donors and patients with type 2 diabetes mellitus

Więcławska, Bogusława; Różalski, Marcin; Trojanowski, Zygmunt; Watała, Cezary

doi:10.1034/j.1600-0609.2001.066006396.x

Cited by 6 publications

(6 citation statements)

References 34 publications

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“…These results are also in agreement with the studies by others [9]. CD36 is expressed in resting cells and its amount significantly increased after agonist stimulation [11], which was also observed in this study. We demonstrated that the 5-min incubation of whole blood with simvastatin and pravastatin significantly decreased CD36 expression in collagen-or ADP-agonized platelets in healthy volunteers.…”

Section: Discussionsupporting

confidence: 94%

Pravastatin and simvastatin improves acetylsalicylic acid‐mediated in vitro blood platelet inhibition

Luzak

Rywaniak

Stanczyk

et al. 2012

Eur J Clin Investigation

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Our results suggested that statins may directly interact with platelet membranes or may modulate a signalling pathway in platelets (the pleiotropic effects of statins). It is possible that the statin effect on CD36 and ASA-mediated protein acetylation can be reached by the modulation of a distribution or a function of membrane-associated proteins. Further studies are certainly needed to better elucidate the mechanism(s) underlying the statins' effects on platelet sensitivity to ASA.

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Section: Discussionsupporting

confidence: 94%

Pravastatin and simvastatin improves acetylsalicylic acid‐mediated in vitro blood platelet inhibition

Luzak

Rywaniak

Stanczyk

et al. 2012

Eur J Clin Investigation

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“…Due to enhanced Ca +2 mobilisation in platelets of diabetic patients, TSP release and binding is likely to be augmented in diabetes. The altered release and binding of TSP to platelets from diabetic patients and its relevance to the impaired platelet calcium mobilisation in the presence of calcium modulators has been suggested [124,141,149,167,170,171]. The incidental reports have suggested that level of TSP bound to circulating platelets is elevated not only in IDDM patients with diabetic cardiovascular microangiopathy, but also those with newly diagnosed diabetes [170,171].…”

Section: Thrombospondinmentioning

confidence: 94%

“…In the course of platelet activation TSP becomes released from intraplatelet granules and the ongoing Ca 2+ mobilisation and its traffic outside platelets facilitates TSP binding to platelet surface membranes. Thus, Ca 2+ mobilisation and release in diabetic platelets support TSP binding in a double way: indirectly, via enhancing Ca 2+ -depended cellular signaling, and directly -via promoting the interaction of TSP with its receptor(s) [167].…”

Section: Thrombospondinmentioning

confidence: 99%

“…This functional association between the fluctuations in a concentration of intraplatelet calcium and platelet membrane dynamics has further implications for the impaired platelet functioning in diabetes. Diabetic platelets have been shown to be more vulnerable to stimuli facilitating cytosolic [Ca 2+ ] mobilisation, and, on the other hand, less susceptible to to preventive effects of the agents hampering calcium release from intraplatelet storage pools [167].…”

Section: Enhanced Calcium Mobilisationmentioning

confidence: 99%

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Blood Platelet Reactivity and its Pharmacological Modulation in (People with) Diabetes Mellitus

Watała

2005

CPD

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Blood platelets play a crucial role in physiological haemostasis and in pathology of prothrombotic states, including atherosclerosis. In this paper, we review major factors underlying altered platelet reactivity, with special attention paid to abnormalities in platelet function in people with diabetes mellitus (DM). The overall picture of platelet abnormalities in DM, including altered adhesion and aggregation, is hypersensitivity of diabetic platelets to agonists. "Primed" diabetic platelets respond more frequently even to subthreshold stimuli, sooner become exhausted, consumed and finally hyposensitive, thus contributing to accelerated thrombopoiesis and release of 'fresh' hyperreactive platelets. In diabetes disturbed carbohydrate and lipid metabolism may lead to physicochemical changes in cell membrane dynamics, and consequently result in altered exposure of surface membrane receptors. These phenomena, together with increased fibrinogen binding, prostanoid metabolism, phosphoinositide turnover and calcium mobilisation often present in diabetic patients, contribute to enhanced risk of small vessel occlusions and accelerated development of atherothrombotic disease of coronary, cerebral and other vessels in diabetes. As platelet hypersensitivity in DM makes a major contribution to enhanced risk of thromboembolic macroangiopathy, and consequently enhanced morbidity and mortality, it validates use of antiplatelet agents in diabetic individuals. Platelet hyperreactivity may be cured with various antiplatelet drugs to a considerably large extent notwithstanding, evidence gathered from clinical and experimental surveys shows that this approach may not always be equally efficient in people with diabetes. Observations from clinical studies rather support the use of multifactorial strategy under such circumstances, like a combined therapy of aspirin plus either purinoreceptor blocker or GPIIb-IIIa antagonist.

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“…In addition, the importance of CD36 in atherogenesis has been demonstrated, since transgenic mice with a deletion of both Cd36 and apoE develop 77% less lesion area than control apoE knockout mice (21). Given that CD36 expression has been reported to be similar in platelets from humans with type 2 diabetes and controls (36), it is plausible that the high levels of markers of platelet activation in type 2 diabetes (3-5) result from triglyceride-enhanced platelet activation via CD36 rather than changes in platelet CD36 expression per se.…”

Section: Cd36 Vldl and Platelet Activationmentioning

confidence: 99%

A Novel Role for CD36 in VLDL-Enhanced Platelet Activation

et al. 2003

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Type 2 diabetes is characterized by increased plasma triglyceride levels and a fourfold increase in ischemic heart disease, but the mechanism is unclear. CD36 is a receptor/transporter that binds fatty acids of lipoproteins. CD36 deficiency has been linked with insulin resistance. There is strong evidence of in vivo interaction between platelets and atherogenic lipoproteins suggesting that atherogenic triglyceride-rich lipoproteins, such as VLDL, that are increased in diabetic dyslipidemia are important in this process. This study demonstrates that VLDL binds to the platelet receptor CD36, enhances platelet thromboxane A2 production, and causes increased collagen-mediated platelet aggregation. VLDL enhanced collagen-induced platelet aggregation by 1) shortening the time taken for aggregation to begin (lag time) to 70% of control (P ‫؍‬ 0.001); 2) increasing maximum aggregation to 170% of control (P ‫؍‬ 0.008); and 3) increasing thromboxane production to 3,318% of control (P ‫؍‬ 0.004), where control represents platelets stimulated with collagen (100%). A monoclonal antibody against CD36 attenuated VLDLenhanced collagen-induced platelet aggregation by 1) inhibiting binding of VLDL to platelets by 75% (P ‫؍‬ 0.041); 2) lengthening lag time to 190% (P < 0.001); and 3) decreasing thromboxane production to 8% of control (P < 0.001). In support of this finding, platelets from Cd36-deficient rats showed no increase in aggregation, thromboxane production, and VLDL binding in contrast to platelets from rats expressing CD36. These data suggest that platelet Cd36 has a key role in VLDLinduced collagen-mediated platelet aggregation, possibly contributing to atherothrombosis associated with increased VLDL levels. Diabetes 52:1248 -1255, 2003 I ndividuals with type 2 diabetes have at least four times greater risk of developing ischemic heart disease (IHD) than the general population. Type 2 diabetes and the metabolic syndrome are also associated with the atherogenic lipoprotein phenotype (1), characterized by elevated plasma triglyceride, increased VLDL production, increased small dense LDL levels, as well as decreased HDL. Recent data provide convincing evidence that increased plasma triglyceride levels are an independent risk factor for IHD (2), but the mechanism linking increased plasma triglyceride-rich lipoproteins, such as VLDL, to IHD remains uncertain.Type 2 diabetes is associated with increased plasma markers of platelet activation (3-5), and pharmacological intervention to reduce plasma triglycerides results in reduction in markers of platelet activation (6). Platelet activation plays an integral role in atherothrombosis (7), since platelet aggregation forms the scaffolding for the initiation of a platelet plug after damage to the vascular wall or rupture of atherosclerotic plaque. It is increasingly apparent that atherogenic lipoproteins and platelets interact both in vivo and in vitro, producing a procoagulant phenotype (8 -11), but the molecular interaction between triglycerides and platelets has not been elucida...

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Modulators of intraplatelet calcium concentration affect the binding of thrombospondin to blood platelets in healthy donors and patients with type 2 diabetes mellitus

Abstract: Both the release of TSP and CD36 presentation are under the influence of agents modulating intracellular Ca2+. Diabetic platelets seem more vulnerable to the releasers of cytosolic [Ca2+] and more resistant to the blockers of cytosolic [Ca2+] mobilisation.

Cited by 6 publications

References 34 publications

Pravastatin and simvastatin improves acetylsalicylic acid‐mediated in vitro blood platelet inhibition

Pravastatin and simvastatin improves acetylsalicylic acid‐mediated in vitro blood platelet inhibition

Blood Platelet Reactivity and its Pharmacological Modulation in (People with) Diabetes Mellitus

A Novel Role for CD36 in VLDL-Enhanced Platelet Activation

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