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Influence of Low Density Lipoprotein from Insulin-Dependent Diabetic Patients on Platelet Functions

Department of Diabetology, INRCA Hospital; Institute of Biochemistry, University of Ancona School of Medicine (D.M., G.C., L.M.); and the Department of Clinical Chemistry, Torrette Hospital (F.R.), 60131 Ancona, Italy; and the Institute of Biochemistry, University of Rangueil (N.D.), Toulouse, France

Address all correspondence and requests for reprints to: Prof. L. Mazzanti, Institute of Biochemistry, Via Ranieri 65, 60131 Ancona, Italy.

In the present work we studied in vitro the action of low density lipoproteins (LDL) isolated from normolipemic insulin-dependent diabetic (IDDM) patients on transmembrane cation transport, nitric oxide synthase (NOS) activity, and aggregating response to stimuli of platelets from healthy subjects to elucidate whether the modified interaction between circulating lipoproteins and cells might be one of the pathogenetic mechanisms of the increased platelet activation in IDDM. LDL were obtained by discontinuous gradient ultracentrifugation from 15 IDDM out-patients and 15 sex- and age-matched healthy subjects and used for incubation experiments with control platelets. Lipid composition and hydroperoxide concentrations were studied in LDL. Platelet aggregation responses to ADP, NOS activity, cytosolic Ca²⁺ concentrations, and platelet membrane Na⁺/K⁺-adenosine triphosphatase (Na⁺/K⁺-ATPase) and Ca²⁺-ATPase activities were measured after incubation. IDDM LDL showed an increased lysophosphatidylcholine content compared with that of control LDL. IDDM LDL significantly increased the platelet aggregating response to ADP, cytosolic Ca²⁺ concentrations, and plasma membrane Ca²⁺-ATPase activity and significantly reduced NOS activity and platelet membrane Na⁺/K⁺-ATPase activity compared with those of platelets incubated in buffer or cells incubated with control LDL. The effects exerted by IDDM LDL on platelet suspensions from healthy subjects mimic the alterations observed in platelets from diabetic subjects in basal conditions Both the decreased activity of NOS and the higher cytoplasmic concentrations of Ca²⁺ might cause increased platelet activation, as observed in IDDM. In conclusion, the present study suggests a new mechanism with a potential role in the early development of atherosclerosis in diabetic patients, i.e. an altered interaction between circulating lipoproteins and platelets.

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