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Glycated Low Density Lipoproteins Modify Platelet Properties: A Compositional and Functional Study

Institute of Biochemistry, University of Ancona School of Medicine; Department of Diabetology, INRCA Hospital (R.A.R.); and Department of Clinical Chemistry, Torrette Hospital (F.R.), 60131 Ancona, Italy

Address all correspondence and requests for reprints to: Prof. Laura Mazzanti, Institute of Biochemistry, University of Ancona, Via P. Ranieri 65, 60131 Ancona, Italy. E-mail: . mazzanti{at}popcsi.unian.it

Abstract

The interaction between low density lipoproteins (LDL) and platelets might play a central role in the development of atherosclerosis in diabetes. The aim of the present study was to investigate whether the glycation of LDL is associated with modifications of their physico-chemical and functional properties and to study the action of glycated LDL (glycLDL) on platelets. LDL and platelets were isolated from 15 healthy subjects. The content of thiobarbituric acid-reactive substances and the generalized polarization of the fluorescent probe Laurdan were determined in LDL glycated in vitro. Platelets were incubated with native LDL, GlycLDL, and minimally oxidized LDL, and the following parameters were evaluated: platelet aggregation, nitric oxide production, intracellular Ca²⁺ concentrations, Na⁺/K⁺-adenosine triphosphatase (Na⁺/K⁺-ATPase), and Ca²⁺-ATPase activities. GlycLDL showed increased thiobarbituric acid-reactive substance levels, a red shift of the Laurdan emission maximum, and a decrease in generalized polarization, indicating a higher polarity and a reduced molecular order compared with native LDL. GlycLDL caused a significant increase in platelet nitric oxide production, intracellular Ca²⁺ concentration, and aggregating response to ADP; an inhibition of the platelet membrane Na⁺/K⁺-ATPase activity; and a stimulation of Ca²⁺-ATPase activity. Minimally oxidized LDL did not cause statistically significant changes in the parameters studied. The present work demonstrates that glycation induces compositional and structural changes in LDL and suggests that an altered interaction between glycLDL and platelets might play a role in the vascular complications of diabetes.

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