Metabolomics analysis of rat blood in atherosclerosis modelling

Introduction. Atherosclerotic changes in blood vessels are one of the main causes of death from cardiovascular diseases worldwide. The use of modern approaches to the study of the disease giving a more detailed description of its pathophysiology may open up additional opportunities for prevention, diagnosis, and treatment. Metabolomics is one of such approaches allows obtaining information on a large number of compounds, the combination of which reflects ongoing metabolic changes. The data presented in this article supplement our previously published study results.

The study aimed to find the relationship between the thickness of the wall of the thoracic aorta in animals on a hyperlipidemic diet and the content of metabolites in the blood.

Materials and methods. The study involved thirty male albino Wistar rats. Atherosclerosis was modelled using a diet consisting of standard feed, simple sugars and fats with the addition of vitamin D3 and Thiamazole. Liquid chromatography with tandem mass spectrometry was used for the metabolomics blood test. Histological sections of rat thoracic aortas were stained with hematoxylin and eosin for the analysis.

Results. Histopathological examination of the thoracic aorta in the animals fed with the atherogenic diet revealed morphological signs of atherosclerosis with severe calcification of the vascular wall. The wall of the thoracic aorta in cases (2.61 ± 0.05 µm) was statistically thicker than in the controls (1.82 ± 0.01 µm) (p < 0.001). Correlation analysis revealed significant negative relationships between thoracic aortic wall thickness and arginine, indole and three of its derivatives, and ketodeoxycholic acid, and positive relationships with glutamate, ophthalmic acid, adenosine diphosphate, two long-chain acylcarnitines, glycocholic acid, oxidized fatty acid, and six lysoglycerophospholipids.

Limitations. The study included only Wistar rats with a limited number of rodents per group.

Conclusion. The relationship between metabolomic alterations in blood and thickness of the wall of the rat thoracic aorta indicates metabolic restructuring typical for atherosclerosis, resulting from oxidative stress, an ongoing inflammatory response, and lipid metabolism disorders characterized by severe calcification, endothelial dysfunction, and increased thrombosis.

Compliance with ethical standards. Study approval was provided by the Local Ethics Committee of the Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers (Protocol No. 1/1 of June 9, 2022).

Contribution:
Unesikhina M.S. — study conception and design, data collection and analysis, draft manuscript preparation;
Chemezov A.I. — study conception and design, data collection and analysis;
Sutunkova M.P. — study conception and design, editing;
Minigalieva I.A. — study conception and design, editing;
Kungurtseva A.K. — data collection and analysis, editing.
All authors are responsible for the integrity of all parts of the manuscript and approval of its final version.

Conflict of interest. The authors declare no conflict of interest.

Acknowledgment. The study had no sponsorship.

Received: October 18, 2024 / Revised: October 29, 2024 / Accepted: November 19, 2024 / Published: December 17, 2024