Carbohydrate composition of circulating multiple-modified low-density lipoprotein

Emile R Zakiev,¹ Igor A Sobenin,^1,2 Vasily N Sukhorukov,¹ Veronika A Myasoedova,¹ Ekaterina A Ivanova,³ Alexander N Orekhov<sup>1,4

1</sup>Laboratory of Angiopathology, Institute for General Pathology and Pathophysiology, ²Laboratory of Medical Genetics, Russian Cardiology Research and Production Complex, Moscow, Russia; ³Department of Development and Regeneration, KU Leuven, Leuven, Belgium; ⁴Skolkovo Innovative Center, Institute for Atherosclerosis Research, Moscow, Russia

Abstract: Atherogenic modification of low-density lipoprotein (LDL) plays a crucial role in the pathogenesis of atherosclerosis, as modified LDL, but not native LDL, induces pronounced accumulation of cholesterol and lipids in the arterial wall. It is likely that LDL particles undergo multiple modifications in human plasma: desialylation, changes in size and density, acquisition of negative electric charge, oxidation, and complex formation. In a total LDL preparation isolated from pooled plasma of patients with coronary atherosclerosis and from healthy subjects, two subfractions of LDL could be identified: desialylated LDL bound by a lectin affinity column and normally sialylated (native) LDL that passed through the column. The desialylated LDL subfraction therefore represents circulating modified LDL. In this work, we performed a careful analysis of LDL particles to reveal changes in the composition of glycoconjugates associated with proteins and lipids. Protein fraction of LDL from atherosclerotic patients contained similar amounts of glucosamine, galactose, and mannose, but a 1.6-fold lower level of sialic acid as compared to healthy donors. Lipid-bound glycoconjugates of total LDL from patients with coronary atherosclerosis contained 1.5–2-fold less neutral monosaccharides than total LDL from healthy donors. Patient-derived LDL also contained significantly less sialic acid. Our results demonstrate that carbohydrate composition of LDL from atherosclerotic patients was altered in comparison to healthy controls. In particular, prominent decrease in the sialic acid content was observed. This strengthens the hypothesis of multiple modification of LDL particles in the bloodstream and underscores the clinical importance of desialylated LDL as a possible marker of atherosclerosis progression.

Keywords: atherosclerosis, low density lipoprotein, LDL, modified LDL, desialylation