Endothelium, aging and vascular diseases

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Abstract

Aging of the organism is inextricably linked with endothelial dysfunction and the development of vascular diseases. However, age per se is only one of the factors of vascular aging. Reactive oxygen species (ROS) play an important role in the mechanisms of aging and death of endothelial cells (EC). Senescence of EC can be associated with endothelial reprogramming, when cells acquire an immunological phenotype or are transformed into myofibroblasts (endothelial-immune or endothelial-mesenchymal transition, respectively). Atherosclerosis is perhaps the most well-known vascular pathology that initiates other diseases. Atherosclerosis is one of the most well-known vascular diseases, which initiates other, more severe diseases. The mechanisms of atherosclerosis development are associated not only with an increased level of "bad" cholesterol, but also with the desialylation of lipoproteins and the simultaneous desialylation of EC. Many factors related to heredity, lifestyle, frequency and intensity of infectious diseases cause damage to the EC and early aging of blood vessels, which leads to secondary vascular diseases, accelerated aging of the body, cognitive impairment and the development of neurodegenerative diseases. The review highlights some of these processes, their chronological and functional relationships.

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About the authors

N. V. Goncharov

Research Institute of Hygiene, Occupational Pathology and Human Ecology; Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences

Author for correspondence.
Email: ngoncharov@gmail.com
Russian Federation, Leningradsky Region; St. Petersburg

P. I. Popova

City Polyclinic No. 112

Email: ngoncharov@gmail.com
Russian Federation, St. Petersburg

А. D. Nadeev

Institute of Cell Biophysics of the Russian Academy of Sciences

Email: ngoncharov@gmail.com
Russian Federation, Pushchino

D. A. Belinskaia

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences

Email: ngoncharov@gmail.com
Russian Federation, St. Petersburg

E. A. Korf

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences

Email: ngoncharov@gmail.com
Russian Federation, St. Petersburg

P. V. Avdonin

Koltsov Institute of Development Biology, Russian Academy of Sciences

Email: ngoncharov@gmail.com
Russian Federation, Moscow

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3. Fig. 1. Cholesterol and excess ROS generation are key factors in atherogenesis. The process is enhanced by desialylation of LDL and EC by neuraminidase 1 (NEU1). Attachment of monocytes to the endothelium is facilitated by VCAM-1 expression and selectins. Oxidation and other modifications of LDL induce secretion of MCP-1 (macrophage chemotactic protein-1). In the arterial intima, monocytes mature into macrophages. Macrophages express scavenger receptors such as SRA and CD36, which facilitate the uptake of modified LDL and transformation into foamy macrophages, which are rich in cholesterol esters and free fatty acids. Monocytes/macrophages proliferate in the presence of MCP-1 and macrophage colony-stimulating factor (MCSF). Following antigen-specific activation, T cells infiltrate the intima, secreting interferon-γ, which sends signals that help amplify and sustain the inflammatory response. Macrophages secrete MMPs (matrix metalloproteinases), which promote collagen breakdown, allowing cells to migrate within the plaque. Accumulation and aggregation of oxLDL and macrophage infiltration cause the lipid pool to be converted into a necrotic core.

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4. Fig. 2. Diagram of cause-and-effect relationships that determine the development of vascular diseases, accelerated aging of the body and impairment of cognitive functions.

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