Accepted_test

Proatherogenic potential of oxidative modifications in LDL
by Diana Kiseleva | Rustam Ziganshin | Vasiliy Kuzmin | Vadim Cherednichenko | Ulyana Khovantseva | Anastasia Bogatyreva | Yulia Markina | Alexander Markin | Laboratory of Cellular and Molecular Pathology of Cardiovascular System, Petrovsky National Research Centre of Surgery, Moscow, Russia; Department of Biophysics, Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia | Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia | Biotechnological Faculty, Lomonosov Moscow State University, Moscow, Russia | Laboratory of Cellular and Molecular Pathology of Cardiovascular System, Petrovsky National Research Centre of Surgery, Moscow, Russia | Laboratory of Cellular and Molecular Pathology of Cardiovascular System, Petrovsky National Research Centre of Surgery, Moscow, Russia | Laboratory of Cellular and Molecular Pathology of Cardiovascular System, Petrovsky National Research Centre of Surgery, Moscow, Russia | Laboratory of Cellular and Molecular Pathology of Cardiovascular System, Petrovsky National Research Centre of Surgery, Moscow, Russia | Laboratory of Cellular and Molecular Pathology of Cardiovascular System, Petrovsky National Research Centre of Surgery, Moscow, Russia; Medical Institute, Peoples’ Friendship University of Russia Named after Patrice Lumumba (RUDN University), Moscow, Russia
Abstract ID: 296
Event: BGRS-abstracts
Sections: [Sym 9] Section “Molecular Pathology, Diagnostics, and Therapeutics”

All currently existing theories that explain the process of the initial atherosclerotic lesion formation underline the important role of low-density lipoprotein (LDL) in the development of this pathology. 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.

The purpose of this study was to analyze the existing protein post-translational modifications (PTM) in native LDL samples, i.e. not modified artificially as it is routinely done to obtain protein oxidation in vitro, and assess their connection with the accumulation of cholesterol by macrophages.

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. The cholesterol accumulation in PMA-induced THP-1 cells was analyzed with a biochemical assay.

We analyzed 38 PTM as well as their combinations in 151 identified proteins. Out of the all detected PTM in LDL proteins that could occur during the oxidation of methionine, lysine, cysteine, tyrosine or other amino acids, none of them affected the increased accumulation of cholesterol by macrophages. The authors suggest that other components of LDL may influence the accumulation and inflammation, which may include the abundance of such proteins as: DAP kinase 1, Myomegalin, Suprabasin, Fibronectin.