Effects of three‐month streptozotocin‐induced diabetes in mice on blood platelet reactivity, COX‐1 expression and adhesion potential

Abstract

Diabetes is associated with an increased risk of cardiovascular disease. This is partially attributed to an altered activation status of blood platelets in this disease. Previously, alterations have been shown in COX-1 and protease activated receptor (PAR)-3 receptor expression in platelets in two animal models of diabetes, there have not been studies which address expression of these proteins in mice with long-term streptozotocin (STZ)-induced diabetes. We have also addressed the effect of diabetes on platelet adhesion under flow conditions. With the use of flow cytometry, we have shown that certain markers of platelet basal activation, such as active form of α IIb β 3 and of CD40L were increased in STZ-induced diabetic mice. Platelets from STZ-induced diabetic mice were also more reactive when stimulated with PAR-4 activating peptide as revealed by higher expression of active form of α IIb β 3 , membrane-bound on vWillebrand Factor and binding of exogenous fluorescein isothyanate-labelled fibrinogen.Expression of COX-1 and production of thromboxane A 2 in platelets of STZ-induced diabetic mice were higher than in control animals. We observed no effect of diabetes on ability of platelets to form stable adhesions with fibrinogen in flow conditions. We conclude that although certain similarities exist between patterns of activation of platelets in animal models of diabetes, the differences should also be taken into account. K E Y W O R D Scell adhesion, diabetes, platelets, prostanoids 42 | PRZYGODZKI et al.

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

“…At the same time, there are conflicting reports on platelet adhesion under flow conditions in vitro in animal models of diabetes. No such increased interactions were observed in our previous in vitro studies in mice with 3-month STZ-induced diabetes [28]. However, it was recently shown that platelets from STZ diabetic mice adhered to a higher extent to fibrinogen in flow conditions in vitro [29].…”

Duration of the diabetic state altered platelet indices from baseline values in a streptozotocin‐induced rat model for type 1 diabetes mellitus

“…According to Przygodzki et al, 14 platelets of mice with 3 months of STZ‐induced diabetes show increased COX‐1 expression and TXA1 production, like other diabetic animal models. However, they differ from the deb/deb mouse model of diabetes, in terms of the simultaneous basal activation and reactivity.…”

“…These two phenomena lead to proaggregatory prostanoids being more prevalent than antiaggregatory prostanoids. Additionally, platelet reactivity increases their ability to adhere to blood vessel walls, which contributes to atherosclerosis 13,14 …”

“…Additionally, platelet reactivity increases their ability to adhere to blood vessel walls, which contributes to atherosclerosis. 13,14 Although higher platelet reactivity is widely accepted among diabetics, findings from research studies on their function are inconsistent, especially in those with T1DM. 15,16 Furthermore, platelet aggregation in murine models of STZ-induced DM has also not been shown to be greater in diabetic than nondiabetic animals.…”

Platelet Glycoprotein-Ib (GPIb) May Serve as a Bridge between Type 2 Diabetes Mellitus (T2DM) and Atherosclerosis, Making It a Potential Target for Antiplatelet Agents in T2DM Patients

“…A study shows that in mice with streptozosocin-induced diabetes, platelets have more frequent interactions with endothelial vessels. This interaction is due to increased expression of vWF in endothelial cells and is mediated by platelet GPIb-IX-V [71].…”