Circulating Immune Complexes and Platelet Thromboxane Synthesis in Patients with Insulin-dependent (Type I) Diabetes Mellitus

Triolo, Giovanni; Davı̀, Giovanni; Giardina, E; Cardella, Francesca; Meli, Francesco; Grutta, A La; Strano, A; Bompiani, G

doi:10.2337/diab.33.8.728

Cited by 7 publications

(2 citation statements)

References 10 publications

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“…In particular, in the last years, immunological factors such as circulating immune complexes [34,35], and antibodies with antiproteoglycan [36] and antiendothelial cell reactivity [4] have been detected in diabetes and considered to play an important part in complement activation and in the pathogenesis or progression of diabetic angiopathy. Moreover, although this was not the object of the present study, it is interesting to note the observation that the distinguishing feature that decides whether cells or certain particles will or will not activate complement could be the amount of sialic acid or sulphated mucopolysaccharides present on the surfaces [37,38].…”

Section: Discussionmentioning

confidence: 99%

Glucose-induced loss of glycosyl-phosphatidylinositol-anchored membrane regulators of complement activation (CD59, CD55) by in vitro cultured human umbilical vein endothelial cells

et al. 2000

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Several lines of evidence suggest that one of the primary events in the course of diabetic vascular pathology is an alteration affecting the endothelial cell function, including abnormalities of vessel tone and permeability, coagulation, blood flow, basement membrane synthesis and turnover and the appearance of specific adhesive glycoproteins promoting the binding and migration of mononuclear cells [1,2]. Hyperglycaemia and immunological factors could trigger the development of these abnormalities [3,4].Many findings show that activation of a complement system occurs in diabetic patients. Complement Diabetologia (2000) 43: 1039±1047Glucose-induced loss of glycosyl-phosphatidylinositol-anchored membrane regulators of complement activation (CD59, CD55) by in vitro cultured human umbilical vein endothelial cells Abstract Aims/hypothesis. This study examines whether increased glucose concentrations are responsible for a decreased expression of membrane regulators of complement activation molecules. The effect of high glucose in determining an increase in membrane attack complex deposition on endothelial cells was also investigated. Methods. Endothelial cells were isolated from umbilical cord tissue, cultured in the presence of increased concentrations of glucose, and the expression of CD46, CD55, and CD59 was detected by ELISA (enzyme-linked immunosorbent assay) and by flow cytometry. Glucose-treated endothelial cells were also incubated with antiendothelial cell antibodies and fresh complement to assess the amount of membrane attack complex formation. Results. High concentrations of glucose decreased the expression of CD59 and CD55 by endothelial cells in a time-dependent and glucose concentration-dependent manner without affecting CD46 expression. High concentrations of soluble CD59 were found in the supernatants of cells treated with high glucose. The decrease in CD59 expression induced by high glucose concentrations was reversed by coincubation of cells with a calcium channel blocking agent (Verapamil). All of these effects were not reproduced by osmotic control media. Cells treated with concentrations of high glucose were more susceptible to complement activation and membrane attack complex formation after exposure to antiendothelial cell antibodies. Conclusion/Interpretation. We speculate that hyperglycaemia could directly contribute to a loss of CD59 and CD55 molecules through a calcium-dependent phosphoinositol-specific phospholipase C activation and subsequent regulation of cell wall expression of GPI-anchored proteins. This phenomenon could facilitate the activation of a complement pathway and could play a part in the aetiology of endothelial dysfunction in diabetes. [Diabetologia (2000

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Section: Discussionmentioning

confidence: 99%

Glucose-induced loss of glycosyl-phosphatidylinositol-anchored membrane regulators of complement activation (CD59, CD55) by in vitro cultured human umbilical vein endothelial cells

et al. 2000

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“…Although there has been an expanding pool of literature on the enhanced platelet sensitivity to a variety of aggregating agents in vitro in T2DM [26], it is not clear at this time whether these abnormalities are intrinsic to the platelet or are a consequence of circulating factors that affect platelet function, as has been demonstrated for insulin immunocomplexes [26,27]. Recent studies indicate that the altered platelet function characteristic of DM may be related to several mechanisms, among which metabolic alterations, oxidative stress and endothelial dysfunction seems to play a pivotal role.…”

Section: Determinants Of In Vivo Platelet Activation In Diabetes Mellmentioning

confidence: 99%

Platelet activation in type 2 diabetes mellitus

Ferroni¹,

Basili

Falco

et al. 2004

Journal of Thrombosis and Haemostasis

396

288

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The abnormal metabolic state that accompanies diabetes renders arteries susceptible to atherosclerosis, being capable of altering the functional properties of multiple cell types, including endothelium and platelets. In particular, an altered platelet metabolism and changes in intraplatelet signaling pathways may contribute to the pathogenesis of atherothrombotic complications of diabetes. A variety of mechanisms may be responsible for enhanced platelet aggregation. Among them, hyperglycemia may represent a causal factor for in vivo platelet activation, and may be responsible for nonenzymatic glycation of platelet glycoproteins, causing changes in their structure and conformation, as well as alterations of membrane lipid dynamics. Furthermore, hyperglycemia-induced oxidative stress is responsible for enhanced peroxidation of arachidonic acid to form biologically active isoprostanes, which represents an important biochemical link between impaired glycemic control and persistent platelet activation. Finally, increased oxidative stress is responsible for activation of transcription factors and expression of redox-sensitive genes leading to a phenotypic switch of endothelium toward an adhesive, prothrombotic condition, initial platelet activation, adhesion and subsequent platelet aggregate formation. All this evidence is strengthened by the results of clinical trials documenting the beneficial effects of metabolic control on platelet function, and by the finding that aspirin treatment may even be more beneficial in diabetic than in high-risk non-diabetic patients. Attention to appropriate medical management of diabetic patients will have great impact on long-term outcome in this high-risk population. © 2004 International Society on Thrombosis and Haemostasis

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Are the vascular complications of diabetes mellitus preceded by an altered thromboxane/prostacyclin plasmatic ratio?

et al. 1986

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Circulating Immune Complexes and Platelet Thromboxane Synthesis in Patients with Insulin-dependent (Type I) Diabetes Mellitus

Cited by 7 publications

References 10 publications

Glucose-induced loss of glycosyl-phosphatidylinositol-anchored membrane regulators of complement activation (CD59, CD55) by in vitro cultured human umbilical vein endothelial cells

Glucose-induced loss of glycosyl-phosphatidylinositol-anchored membrane regulators of complement activation (CD59, CD55) by in vitro cultured human umbilical vein endothelial cells

Platelet activation in type 2 diabetes mellitus

Are the vascular complications of diabetes mellitus preceded by an altered thromboxane/prostacyclin plasmatic ratio?

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