Enhanced P-selectin expression and increased soluble CD40 Ligand in patients with Type 1 diabetes mellitus and microangiopathy: evidence for platelet hyperactivity and chronic inflammation

Abstract

Aims/hypothesis. Platelet activation, endothelial dysfunction and inflammation may be involved in early stages of diabetic microangiopathy. We therefore investigated patients with Type 1 diabetes mellitus, without (n=19) and with (n=20) microangiopathy, matched for glycaemic control and duration of disease, and matched with healthy control subjects (n=27). Methods. Platelet activation was measured as platelet P-selectin expression using whole blood flow cytometry and as soluble P-selectin by immunoassay. Von Willebrand factor antigen in plasma, serum soluble Eselectin, CD40 ligand (sCD40L) and C-reactive protein (CRP) served as markers for endothelial function and inflammation. Results. Thrombin-induced platelet P-selectin expression was enhanced, and soluble P-selectin and sCD40L concentrations were increased in patients with microangiopathy compared with the control subjects (p<0.01 for both) and with patients without microangiopathy (p<0.05 for P-selectin expression and sP-selectin), whereas all three parameters were similar in patients without microangiopathy and in the control subjects. CRP and soluble E-selectin were increased in patients with microangiopathy, compared with the control subjects (p<0.01 and p<0.05), whereas von Willebrand factor did not differ between the groups. Conclusions/interpretation. Microangiopathy in Type 1 diabetes is associated with platelet hyperactivity, endothelial dysfunction and low-grade inflammation, indicating an increased risk for cardiovascular disease. [Diabetologia (2004) 47:537-540]

Soluble CD40 Iigand and Oxidative Response Are Reciprocally Stimulated during Shiga Toxin-Associated Hemolytic Uremic Syndrome

“…The sCD40L plasmatic values showed by HUS patients were similar to those reported in other pathological conditions such as cardiovascular diseases, diabetes, HIV infection or smokers [41,[45][46][47][48][49] and it can be considered as a marker of thrombotic risk [26]. Therefore, and based on the present results, we propose that quantification of sCD40L in plasma could be used as a surrogate and early marker of microvascular dysfunction and/or platelet activation in Stx-associated diarrheas.…”

CD40 Mediates Retinal Inflammation and Neurovascular Degeneration

“…These overlapping features between diabetic and I/R-induced retinopathies raise the possibility that CD40 is a mediator also of diabetic retinopathy. Relevant to this possibility is the evidence that points to activation of the CD40-CD154 pathway in diabetic retinopathy, because CD154 expression is increased in patients with this disease (48,49).…”

CD40–CD40L: Linking pancreatic, adipose tissue and vascular inflammation in type 2 diabetes and its complications

“…Interestingly, T2DM is independently associated with elevated sCD40L levels in patients suffering from acute coronary syndromes and myocardial infarction. 49,50 In T1DM, sCD40L levels have been shown to correlate with endothelial dysfunction, monocyte activation and increased numbers of platelet-leukocyte aggregates. 50,51 Although elevated levels of sCD40L were associated with carotid atherosclerosis in T1DM, elevated levels did not predict cardiovascular mortality.…”

“…49,50 In T1DM, sCD40L levels have been shown to correlate with endothelial dysfunction, monocyte activation and increased numbers of platelet-leukocyte aggregates. 50,51 Although elevated levels of sCD40L were associated with carotid atherosclerosis in T1DM, elevated levels did not predict cardiovascular mortality. 52,53 As discussed above, IR, hyperinsulinemia, hyperglycaemia and obesity are all associated with increased sCD40L levels.…”