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Role of Serotonin, Membrane Transporter, and 5-HT2 Receptors in Pathogenesis of Atherosclerotic Plaque Formation in Immature Heterozygous Low-Density Lipoprotein-Receptor-Deficient Mice

Dinara Sadykova,R. Nigmatullina,K. Salakhova,E. Slastnikova,Liliya Galimova,C. Khaliullina,Elena Gafurova,Dmitry E. Tsyplakov

Published 2025 in International Journal of Molecular Sciences

ABSTRACT

Familial hypercholesterolemia leads to the early development of cardiovascular diseases at a young age due to the prolonged exposure of the arterial vessel wall to high concentrations of atherogenic lipids. Serotonin plays a significant role in the development and progression of atherosclerotic processes. Monoamine has a damaging effect on the vascular wall, stimulates the proliferation of vascular smooth muscle cells and fibroblasts, and participates in platelet activation and aggregation. The aim of the work was the demonstration of the importance of serotonin, transporters, and receptors in the pathogenesis of atherosclerotic plaque formation. The study was performed on immature mice of the C57BL/6JGpt-Ldlrem1Cd82/Gpt (Ldlr+/−) line (main group) and C57BL/6 mice of comparable age and sex demographics (control group). Morphological manifestations of early signs of atherosclerosis (pre-lipid stage and lipoidosis stage, which were confirmed by Sudan III staining) in the gene-modified mice’s aorta were determined. Morphological changes in the aorta correlated with changes in the left ventricle of the heart, where lipid content also increased. No atherosclerotic changes in the control-group mice were detected. A statistically significant increase in the expression of the membrane serotonin transporter and 5HT2A and 5HT2B receptors in both the aorta and left ventricle was also found in the animals of the main group. Serotonin and its receptors and transporter may become new therapeutic targets for the treatment and prevention of atherosclerotic vascular lesion progression in children and adults.

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