Lipid composition of circulating multiple-modified low density lipoprotein

Abstract

Atherogenic modified low- density lipoprotein (LDL) induces pronounced accumulation of cholesterol and lipids in the arterial wall, while native LDL seems to lack such capability. Therefore, modified LDL appears to be a major causative agent in the pathogenesis of atherosclerosis. Possible modifications of LDL particles include changes in size and density, desialylation, oxidation and acquisition of negative charge. Total LDL isolated from pooled plasma of patients with coronary atherosclerosis, as well as from healthy subjects contains two distinct subfractions: normally sialylated LDL and desialylated LDL, which can be isolated by binding to a lectin affinity column. We called the desialylated LDL subfraction circulating modified LDL (cmLDL). In this study, we focused on lipid composition of LDL particles, analysing the total LDL preparation and two LDL subfractions: cmLDL and native LDL. The composition of LDL was studied using thin-layer chromatography. We found that cmLDL subfraction had decreased levels of free and esterified cholesterol, triglycerides, phospholipids (except for lysophosphatidylcholine) and sphingomyelin in comparison to native LDL. On the other hand, levels of mono-, and diglycerides, lysophosphatidylcholine and free fatty acids were higher in cmLDL than in native LDL. Our study demonstrated that lipid composition of cmLDL from atherosclerotic patients was altered in comparison to healthy subjects. In particular, phospholipid content was decreased, and free fatty acids levels were increased in cmLDL. 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.

Small dense and desialylated low density lipoprotein in diabetic patients

“…[12,13,23,32] We have found previously that LDL atherogenicity in CAD patients and diabetic patients correlates negatively with sialic acid levels. [13] Indeed, in vitro studies have shown that desialylated LDL treated with neuraminidase, which removes the sialic acid residues, results in a significant increase in LDL potency to induce lipid accumulation in cultured monocyte-macrophages or intimal cells.…”

“…Such separation is possible by using a column with RCA 120 immobilized on CNBractivated agarose. [12,21] Compared with sialylated LDL, desialylated LDL particles are smaller in size and contain more oxysterols, and less phospholipids and antioxidants. [12] In terms of the ability to induce intracellular deposition of lipids, the desialylated LDL fraction is atherogenic.…”

“…[12,21] Compared with sialylated LDL, desialylated LDL particles are smaller in size and contain more oxysterols, and less phospholipids and antioxidants. [12] In terms of the ability to induce intracellular deposition of lipids, the desialylated LDL fraction is atherogenic. [12,23,32] Several studies have reported an elevation of sialic acid serum levels in CHD patients, and also on its correlation with the severity of the coronary lesions.…”

“…[12] In terms of the ability to induce intracellular deposition of lipids, the desialylated LDL fraction is atherogenic. [12,23,32] Several studies have reported an elevation of sialic acid serum levels in CHD patients, and also on its correlation with the severity of the coronary lesions. [33] Diabetic patients' LDL, by the first approach, appeared to have a decreased level of sialic acid, and further investigations have shown that this was due to an increased proportion of desialylated LDL fraction in patients' blood and a greater extent of its desialylation.…”

“…[10,11] It was hence accepted that LDL is required to undergo structural alterations or chemical modifications to become atherogenic. [12] However, modified LDL particles are still not considered as clinical biomarkers or therapeutic targets because of insufficient evidence. Therefore, additional studies, both basic and clinical, are necessary to fill the existing gap in the knowledge.…”