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血清素、膜转运体和5-羟色胺2受体在未成熟杂合低密度脂蛋白受体缺陷小鼠动脉粥样硬化斑块形成发病机制中的作用

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

作者信息

Sadykova Dinara, Nigmatullina Razina, Salakhova Karina, Slastnikova Evgeniia, Galimova Liliya, Khaliullina Chulpan, Gafurova Elena, Tsyplakov Dmitry

机构信息

Department of Hospital Pediatrics, Kazan State Medical University, 420012 Kazan, Russia.

Department of Normal Physiology, Kazan State Medical University, 420012 Kazan, Russia.

出版信息

Int J Mol Sci. 2025 Jun 26;26(13):6184. doi: 10.3390/ijms26136184.

DOI:10.3390/ijms26136184
PMID:40649961
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12250590/
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-Ldlr/Gpt () 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.

摘要

家族性高胆固醇血症会导致年轻人在年轻时就早早患上心血管疾病,这是由于动脉血管壁长期暴露于高浓度的致动脉粥样硬化脂质中。血清素在动脉粥样硬化过程的发生和发展中起着重要作用。单胺对血管壁有损害作用,刺激血管平滑肌细胞和成纤维细胞的增殖,并参与血小板的激活和聚集。这项工作的目的是证明血清素、转运体和受体在动脉粥样硬化斑块形成发病机制中的重要性。该研究在C57BL/6JGpt-Ldlr/Gpt()品系的未成熟小鼠(主要组)和年龄及性别相当的C57BL/6小鼠(对照组)上进行。确定了基因修饰小鼠主动脉中动脉粥样硬化早期迹象(通过苏丹III染色证实的前脂质阶段和类脂沉积阶段)的形态学表现。主动脉的形态学变化与心脏左心室的变化相关,心脏左心室的脂质含量也增加。对照组小鼠未检测到动脉粥样硬化变化。在主要组的动物中,还发现主动脉和左心室中膜血清素转运体以及5HT2A和5HT2B受体的表达有统计学意义的增加。血清素及其受体和转运体可能成为治疗和预防儿童和成人动脉粥样硬化性血管病变进展的新治疗靶点。

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