Platelet Adhesion and Aggregate Formation in Type I Diabetes Under Flow Conditions

Nievelstein, P F; Sixma, Jan J.; Ottenhof-Rovers, Mieke; Wynne, Harold; Groot, Philip G. de; Banga, Jan Dirk

doi:10.2337/diab.40.11.1410

Cited by 15 publications

(5 citation statements)

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“…To our knowledge, these studies were the first to evaluate firm platelet adhesion from diabetic patients under flow conditions to fibrinogen and vWF. A previous report on platelets adhesion under flow conditions to matrices formed by endothelial cells or fibroblasts showed no difference between the adhesion of platelets from diabetic patients and non-diabetic individuals [27]. At the same time, there are conflicting reports on platelet adhesion under flow conditions in vitro in animal models of diabetes.…”

Section: Evaluation Of Adhesion Potential Of Platelets From Diabetic Patientsmentioning

confidence: 93%

Diabetes and Hyperglycemia Affect Platelet GPIIIa Expression: Effects on Adhesion Potential of Blood Platelets from Diabetic Patients under In Vitro Flow Conditions

Przygodzki

Luzak

Kassassir

et al. 2020

IJMS

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Blood platelets play a crucial role in the early stages of atherosclerosis development. The process is believed to require firm adhesion of platelets to atherosclerosis-prone sites of the artery. However, little evidence exists regarding whether the blood platelets of individuals with pathological conditions associated with atherosclerosis have higher potential for adhesion. This process is to a large extent dependent on receptors present on the platelet membrane. Therefore, the aim of the presented study was to determine whether blood platelets from diabetic patients have higher capacity of adhesion under flow conditions and how diabetes affects one of the crucial platelet receptors involved in the process of adhesion—GPIIIa. The study compares the ability of platelets from non-diabetic and diabetic humans to interact with fibrinogen and von Willebrand factor, two proteins found in abundance on an inflamed endothelium, under flow conditions. The activation and reactivity of the blood platelets were also characterized by flow cytometry. Platelets from diabetic patients did not demonstrate enhanced adhesion to either studied protein, although they presented increased basal activation and responsiveness towards low concentrations of agonists. Platelets from diabetic patients were characterized by lower expression of GPIIIa, most likely due to an enhanced formation of platelet-derived microparticles PMPs, as supported by the observation of elevated concentration of this integrin and of GPIIIa-positive PMPs in plasma. We conclude that altered functionality of blood platelets in diabetes does not increase their adhesive potential. Increased glycation and decrease in the amount of GPIIIa on platelets may be partially responsible for this effect. Therefore, higher frequency of interactions of platelets with the endothelium, which is observed in animal models of diabetes, is caused by other factors. A primary cause may be a dysfunctional vascular wall.

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Section: Evaluation Of Adhesion Potential Of Platelets From Diabetic Patientsmentioning

confidence: 93%

Diabetes and Hyperglycemia Affect Platelet GPIIIa Expression: Effects on Adhesion Potential of Blood Platelets from Diabetic Patients under In Vitro Flow Conditions

Przygodzki

Luzak

Kassassir

et al. 2020

IJMS

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“…Adherence of platelets from poorlycontrolled diabetic subjects to glass surfaces coated with glycated or unglycated collagen is not different from platelets from control subjects [14]. Also, ac-cumulation of platelets from diabetic subjects on extracellular matrix from control endothelial cells in vitro is similar to control platelets [15]. · In response to single injury to the aorta with a balloon catheter in vivo, the number of platelets which initially accumulates on the injured surface is similar in control and diabetic rats.…”

Section: Effect Of Diabetes On Platelet Accumulation and Turnover On mentioning

confidence: 99%

Platelet turnover in advanced diabetes

1994

Eur J Clin Investigation

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There is considerable information to indicate that when there is vessel injury, platelets can play a major role in the development of atherosclerosis and its thromboembolic complications in the non-diabetic population. Diabetes is a disease associated with an increased risk of vascular complications, but the nature of this association is unclear. Platelets from diabetic humans and animals are hypersensitive to agonists in vitro, but it is unclear if this hypersensitivity persists in vivo. Platelets survival and turnover in the circulation have been used as indicators of platelet behaviour in vivo, but platelet survival measurements do not necessarily correlate with platelet sensitivity in vitro and these measurements may be too insensitive to reflect platelet turnover on injured vessels or in thrombi, unless there is extensive vascular disease. Studies in rats and rabbits indicate that diabetes causes increased platelet interaction with experimentally-injured vessels and accumulation in thrombi. It is unclear, however, whether this altered behaviour of platelets at the injured vessel surface reflects changes in the platelets or in the vessel wall and whether it contributes to the increased risk for vascular complications in diabetic patients.

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“…prostacyclin, ADPase, and NO, among others), anticoagulant substances (thrombomodulin and heparin-like substances, among others), and fibrinolysis stimulators (tissue plasminogen activator, or tPA) [57]. These functions are impaired in diabetes mellitus, and many studies have reported increased platelet activation in the plasma phase of coagulation, along with deficient fibrinolytic activity [8,29,54,[57][58][59]. These changes tend to favor a prothrombotic state in patients with diabetes, a situation that leads in turn to a higher risk of myocardial infarction, stroke, amputation, and vascular death [60].…”

Section: Altered Antithrombotic Functionmentioning

confidence: 99%

“…These changes lead to the prothrombotic state, which can favor the appearance of retinal ischemia [8,29,54,[57][58][59]. Therefore, one of the preventive measures that can be used for diabetic retinopathy is based on drugs that inhibit platelet activity while sparing or even enhancing endothelial antithrombotic function [8].…”

Section: Modulation Of the Antithrombotic Function Of The Endotheliummentioning

confidence: 99%

Pharmacological approach to diabetic retinopathy

Cruz

González-Correa

Guerrero

et al. 2004

Diabetes Metabolism Res

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Diabetic retinopathy is the most frequent cause of legal blindness in the population of 30-to-70-year olds. Whether retinopathy appears or not depends mainly on the duration of the disease and the degree of metabolic control the patient maintains. High blood glucose values lead to important changes in cellular metabolism and the main effects of these alterations are endothelial dysfunction that sets in motion the morphological process of diabetic retinopathy. The biochemical lesions caused by prolonged hyperglycemia can be positively influenced, but usually not normalized, pharmacologically with some groups of drugs, which are now under development. This makes tight control of glycemia a key measure in preventing the onset or progression of diabetic retinopathy, together with an effective program of ophthalmologic detection and follow-up in patients with diabetes. Regarding the role of endothelial dysfunction, antiplatelet drugs have been shown to slow some aspects of the evolution of diabetic retinopathy in its initial stages, mainly a lower degree of microaneurysms. However, a new approach to controlling endothelial dysfunction shows promise, mainly through the vascular endothelial growth factor (VEGF) inhibitors. These agents may prove to be especially useful in the treatment of proliferative diabetic retinopathy. Other encouraging results have been obtained in studies of antioxidant drugs and inhibitors of the formation of advanced glycation end products. Once retinal lesions appear, preventive measures need to be redoubled, with special attention to controlling glycemia; however, it is also necessary to resort to laser photocoagulation. This intervention aims to eliminate areas of ischemia and to diminish the formation of retinal exudates. If this measure fails or if vitreous hemorrhage appears, the only remaining therapeutic measure is vitrectomy.

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Platelet Adhesion and Aggregate Formation in Type I Diabetes Under Flow Conditions

Cited by 15 publications

References 0 publications

Diabetes and Hyperglycemia Affect Platelet GPIIIa Expression: Effects on Adhesion Potential of Blood Platelets from Diabetic Patients under In Vitro Flow Conditions

Diabetes and Hyperglycemia Affect Platelet GPIIIa Expression: Effects on Adhesion Potential of Blood Platelets from Diabetic Patients under In Vitro Flow Conditions

Platelet turnover in advanced diabetes

Pharmacological approach to diabetic retinopathy

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