PROATHEROGENIC PROTEOMIC PROFILE OF LDL ISOLATED FROM PLASMA OF PATIENTS WITH DIABETES MELLITUS: IMMUNOLOGICAL ASPECTS
- Authors: Kiseleva D.G.1,2, Ziganshin R.K.3, Fotin D.P.4, Markin A.M.2,5
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Affiliations:
- Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia
- Petrovsky National Research Center of Surgery, Moscow, Russia
- Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia
- Medical and Biological Faculty, Pirogov Russian National Research Medical University, Moscow, Russia
- Medical Institute, Peoples’ Friendship University of Russia named after Patrice Lumumba (RUDN University), Moscow, Russia
- Section: Joint Immunology Forum 2024
- URL: https://rusimmun.ru/jour/article/view/16674
- DOI: https://doi.org/10.46235//1028-7221-16674-PPP
- ID: 16674
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Abstract
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.
About the authors
Diana G. Kiseleva
Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia;Petrovsky National Research Center of Surgery, Moscow, Russia
Email: trueit1292@gmail.com
ORCID iD: 0000-0001-8149-349X
Scopus Author ID: 58574198100
junior researcher at the Department of Biophysics, Faculty of Biology, Lomonosov Moscow State University; junior researcher, Laboratory of Cellular and Molecular Pathology of the Cardiovascular System, Petrovsky National Research Center of Surgery
Russian FederationRustam Kh. Ziganshin
Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia
Email: ziganshin@mail.ru
Candidate of Chemical Sciences, Senior researcher in the mass spectrometry group, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistr
Russian FederationDenis P. Fotin
Medical and Biological Faculty, Pirogov Russian National Research Medical University, Moscow, Russia
Email: denisiy.fotin@mail.ru
student of the Medical and Biological Faculty, Pirogov Russian National Research Medical University
Russian FederationAlexander M. Markin
Petrovsky National Research Center of Surgery, Moscow, Russia;Medical Institute, Peoples’ Friendship University of Russia named after Patrice Lumumba (RUDN University), Moscow, Russia
Author for correspondence.
Email: alexander.markin.34@gmail.com
ORCID iD: 0000-0002-6649-7924
Scopus Author ID: 57216565313
Candidate of Medical Sciences, Senior researcher at the Laboratory of Cellular and Molecular Pathology of the Cardiovascular System, Petrovsky National Research Center of Surgery
Russian FederationReferences
- Кириченко, Т.В., Бочкарева, Л.А., Недосугова, Л.В., Маркина, Ю.В., Кузина, И.А., Толстик, Т.В., Богатырева, А.И., Маркин, A.M. Взаимосвязь провоспалительной активации моноцитов с факторами риска атеросклероза при сахарном диабете 2 типа // Атеросклероз и Дислипидемиию – 2024. Т. 1, №54. С.45-51 [Kirichenko, T.V., Bochkareva, L.A., Nedosugova, L.V., Markina, Yu.V., Kuzina, I.A., Tolstik, T.V., Bogatyreva, A.I., Markin , A.M. The association of pro-inflammatory monocyte activation and risk factors for atherosclerosis in type 2 diabetes mellitus. Atherosclerosis and dyslipidemias, 2024, Vol. 1, no.54, pp. 45–51]
- Brinkley, T. E., Nicklas, B. J., Kanaya, A. M., Satterfield, S., Lakatta, E. G., Simonsick, E. M., Sutton-Tyrrell, K., Kritchevsky, S. B. Plasma oxidized low-density lipoprotein levels and arterial stiffness in older adults: the health, aging, and body composition study: The Health, aging, and Body Composition Study. Hypertension. 2009, Vol. 53, no. 5, pp. 846–852.
- Cherepanova, O. A., Srikakulapu, P., Greene, E. S., Chaklader, M., Haskins, R. M., McCanna, M. E., Bandyopadhyay, S., Ban, B., Leitinger, N., McNamara, C. A., Owens, G. K. Novel autoimmune IgM antibody attenuates atherosclerosis in IgM deficient low-fat diet–fed, but not Western diet–fedApoe–/–mice. Arteriosclerosis, Thrombosis, and Vascular Biology, 2020, Vol. 40, no. 1, pp. 206–219.
- Höpfinger, A., Karrasch, T., Schäffler, A., & Schmid, A. Circulating levels of cathelicidin antimicrobial peptide (CAMP) are affected by oral lipid ingestion. Nutrients, 2023, Vol. 15, no. 13, pp. 3021.
- Kiss, M. G., Binder, C. J. The multifaceted impact of complement on atherosclerosis. Atherosclerosis, 2022, Vol. 351, pp. 29–40.
- Sakura, T., Morioka, T., Shioi, A., Kakutani, Y., Miki, Y., Yamazaki, Y., Motoyama, K., Mori, K., Fukumoto, S., Shoji, T., Emoto, M., Inaba, M. Lipopolysaccharide-binding protein is associated with arterial stiffness in patients with type 2 diabetes: a cross-sectional study. Cardiovascular Diabetology, 2017, Vol. 16, no. 1.
- Singh, P., Goncalves, I., Tengryd, C., Nitulescu, M., Persson, A. F., To, F., Bengtsson, E., Volkov, P., Orho-Melander, M., Nilson, J., Edsfeldt, A. Reduced oxidized LDL in T2D plaques is associated with a greater statin usage but not with future cardiovascular events. Cardiovasc. Diabetol. 2020, Vol. 19, no. 1, pp. 214.
- Steinberg, D. Atherogenesis in perspective: hypercholesterolemia and inflammation as partners in crime. Nat. Med. 2002, Vol. 8, no. 11, pp. 1211–1217.
- Taylor, J. A., Hutchinson, M. A., Gearhart, P. J., Maul, R. W. Antibodies in action: the role of humoral immunity in the fight against atherosclerosis. Immunity & Ageing: I & A, 2022, Vol. 19, no. 1.
- Tyanova, S., Temu, T., Cox, J. The MaxQuant computational platform for mass spectrometry-based shotgun proteomics. Nature protocols, 2016, Vol. 11, pp. 2301-2319
- Tyanova, S., Temu, T., Sinitcyn, P., Carlson, A., Hein, M. Y., Geiger, T., Mann, M., Cox, J. The Perseus computational platform for comprehensive analysis of (prote)omics data. Nature methods, 2016, Vol. 13, pp. 731-740
- Vreugdenhil, A. C. E., Snoek, A. M. P., van ‘t Veer, C., Greve, J.-W. M., Buurman, W. A. LPS-binding protein circulates in association with apoB-containing lipoproteins and enhances endotoxin-LDL/VLDL interaction. The Journal of Clinical Investigation, 2001, Vol. 107, no. 2, pp. 225–234.
- Xin, Y., Hertle, E., van der Kallen, C. J. H., Vogelzangs, N., Arts, I. C. W., Schalkwijk, C. G., Stehouwer, C. D. A., van Greevenbroek, M. M. J. C3 and alternative pathway components are associated with an adverse lipoprotein subclass profile: The CODAM study. Journal of Clinical Lipidology, 2021, Vol. 15, no. 2, pp. 311–319
- Ye, J., Yang, P., Yang, Y., Xia, S. Complement C1s as a diagnostic marker and therapeutic target: Progress and propective. Frontiers in Immunology, 2022, Vol. 13.