The role of collagen gene polymorphisms in the development of cardiovascular diseases

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Abstract

Background. Collagen fibers are the main component of most types of connective tissue; collagen is the most abundant protein in the human body. The most common types of collagen that provide elasticity and stiffness of the tissue under regular mechanical stress are collagen types I and III. Congenital or acquired changes in collagen are the substrate basis for changes in the vascular wall.

Objective. Characteristics of the current understanding of the role of collagen gene polymorphisms in the development of cardiovascular diseases.

Methods. Articles were selected in PubMed, Google Scholar search engines from February to May 2022. The following keywords were used for the search: polymorphism, collagen, vascular diseases, single nucleotide polymorphism (SNP).

Results. Single nucleotide polymorphisms rs2621215 in the promoter regions of the 7q22.1 genes can affect the collagen expression level, increasing the risk of developing vascular aneurysms. Polymorphism of the α-1-chain type I collagen gene COL1A1 (17q21.31 – q22) leads to the development of cardiovascular diseases associated with an increase in arterial stiffness. Increased vascular stiffness is associated with endothelial dysfunction, increased activity of angiotensin-converting enzyme (ACE). This leads to increased synthesis of angiotensin II and activation of the renin-angiotensin-aldosterone system (RAAS). The endothelial dysfunction may result not only in a decrease in NO production, but also in its accelerated degradation and vascular remodeling. Drugs that increase NO formation, such as nebivolol, can reduce the stiffness of large arteries, reduce central blood pressure, and also have a beneficial effect on the elastic properties of the arteries, which in turn can lead to a decrease in cardiovascular risk.

The tissue effects of ACE inhibitors restore endothelial function, inhibit the proliferation and migration of smooth muscle cells, neutrophils and mononuclear cells, and reduce free radical oxidation. The effect on endothelial dysfunction is probably related to the restoration of bradykinin metabolism. The COL1A2 gene encodes pro-alpha-2 collagen type I chains, whose triple helix also consists of two alpha-1 chains and one alpha-2 chain. Mutations in this gene are associated with cardiovascular type Ehlers-Danlos syndrome. Mutations in the COL3A1 gene cause the vascular type Ehlers–Danlos syndrome. With this type, patients often die suddenly due to rupture of large arteries, vascular aneurysms as a consequence of a decrease in the normal type III collagen level in the vessel wall. Polymorphism of the COL3A1 gene can affect the strength and extensibility of collagen fibers and thereby change the quality of connective tissue.

Conclusion. Violation of collagen synthesis and the structure and mechanical properties of the vascular wall can be the main cause of vascular accidents and occur regardless of the presence of traditional risk factors.

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About the authors

Nadezhda V. Izmozherova

Ural State Medical University

Author for correspondence.
Email: nadezhda_izm@mail.ru

Dr. Sci. (Med.), Associate Professor, Head of the Department of Pharmacology and Clinical Pharmacology, Chief External Expert in Clinical Pharmacology of the Ministry of Health of the Sverdlovsk Region

Russian Federation, Yekaterinburg

A. A. Popov

Ural State Medical University

Email: nadezhda_izm@mail.ru
ORCID iD: 0000-0001-6216-2468
Russian Federation, Yekaterinburg

M. A. Shambatov

Ural State Medical University

Email: nadezhda_izm@mail.ru
ORCID iD: 0000-0001-7312-415X
Russian Federation, Yekaterinburg

E. M. Tarasova

Ural State Medical University

Email: nadezhda_izm@mail.ru
ORCID iD: 0000-0001-9068-0924
Russian Federation, Yekaterinburg

V. M. Bakhtin

Ural State Medical University

Email: nadezhda_izm@mail.ru
ORCID iD: 0000-0001-7907-2629
Russian Federation, Yekaterinburg

L. I. Kadnikov

Ural State Medical University

Email: nadezhda_izm@mail.ru
ORCID iD: 0000-0002-2623-2657
Russian Federation, Yekaterinburg

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