Proatherogenic proteomic profile of LDL isolated from plasma of patients with diabetes mellitus: immunological aspects

Abstract

Atherosclerosis is a vascular disease, which is based on a chronic inflammatory process, including complex interactions between blood components, as well as the cells that form the vessel wall, and lipid metabolism in general. Low-density lipoproteins (LDL) play a key role in pathogenesis of atherosclerosis. When the permeability of the endothelial layer of the vessel is impaired, LDL can penetrate into the intramural space and lead to excessive cholesterol accumulation by the cells from the intima subendothelial layer, leading to the onset of the inflammatory process and to the formation of foam cells, the main morphological component of the atherosclerotic plaque. However, the level of LDL in the patient’s blood plasma alone is not a key indicator of the development of atherosclerosis. Numerous studies point out the role of oxidized modifications of LDL (oxLDL) in the increased local accumulation of cholesterol in vascular wall cells, however, recent works have shown conflicting results regarding the role of oxLDL in the development of atherosclerosis. We hypothesize that other components of LDL may also influence the progression of atherosclerosis. It is a well-known fact that patients with diabetes mellitus (DM) suffer from cardiovascular diseases, in particular atherosclerosis, more often than patients without diagnosed DM and other autoimmune diseases, and the disease progresses faster. The purpose of this study was to identify risk biomarkers in LDL groups that indicate the relationship of the immune system with the development of atherosclerosis in such patients. LDL was isolated from patients and healthy donors using continuous ultracentrifugation with solutions of different densities, and LDL protein profile samples were measured using gas chromatography-mass spectrometry. We found 9 proteins that had a statistically significant difference between the samples (DM and control). In the diabetes group, the content of the antimicrobial peptide cathelicidin and lipopolysaccharide-binding protein was almost 2 times higher compared to the control. These proteins may be involved in the development of inflammation, leading to the progression of atherosclerosis. At the same time, a decrease in immunoglobulins and complement components (C9 and Complement C1s subcomponent) associated with LDL may contribute to the development of atherosclerosis.