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血管间充质干细胞/前体细胞对高脂血症的反应。

Response of vascular mesenchymal stem/progenitor cells to hyperlipidemia.

机构信息

Department of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China.

School of Cardiovascular Medicine and Sciences, King's BHF Centre, 125 Coldharbour Lane, London, SE5 9NU, UK.

出版信息

Cell Mol Life Sci. 2018 Nov;75(22):4079-4091. doi: 10.1007/s00018-018-2859-z. Epub 2018 Jun 26.

Abstract

Hyperlipidemia is a risk factor for atherosclerosis that is characterized by lipid accumulation, inflammatory cell infiltration, and smooth muscle cell proliferation. It is well known that hyperlipidemia is a stimulator for endothelial dysfunction and smooth muscle cell migration during vascular disease development. Recently, it was found that vessel wall contains a variable number of mesenchymal stem cells (MSCs) that are quiescent in physiological conditions, but can be activated by a variety of stimuli, e.g., increased lipid level or hyperlipidemia. Vascular MSCs displayed characteristics of stem cells which can differentiate into several types of cells, e.g., smooth muscle cells, adipocytic, chondrocytic, and osteocytic lineages. In vitro, lipid loading can induce MSC migration and chemokines secretion. After MSC migration into the intima, they play an essential role in inflammatory response and cell accumulation during the initiation and progression of atherosclerosis. In addition, MSC transplantation has been explored as a therapeutic approach to treat atherosclerosis in animal models. In this review, we aim to summarize current progress in characterizing the identity of vascular MSCs and to discuss the mechanisms involved in the response of vascular stem/progenitor cells to lipid loading, as well as to explore therapeutic strategies for vascular diseases and shed new light on regenerative medicine.

摘要

高脂血症是动脉粥样硬化的一个危险因素,其特征是脂质积累、炎症细胞浸润和平滑肌细胞增殖。众所周知,高脂血症是血管疾病发展过程中内皮功能障碍和平滑肌细胞迁移的刺激因素。最近发现,血管壁中含有数量不定的间充质干细胞(MSCs),在生理条件下处于静止状态,但可被多种刺激物激活,如脂质水平升高或高脂血症。血管 MSCs 表现出干细胞的特征,可以分化为多种类型的细胞,如平滑肌细胞、脂肪细胞、软骨细胞和成骨细胞。在体外,脂质负荷可诱导 MSC 迁移和趋化因子分泌。MSC 迁移到内膜后,在动脉粥样硬化的起始和进展过程中,它们在炎症反应和细胞积累中发挥重要作用。此外,MSC 移植已被探索作为治疗动物模型中动脉粥样硬化的一种治疗方法。在这篇综述中,我们旨在总结血管 MSCs 特征的最新进展,并讨论血管干细胞/祖细胞对脂质负荷的反应所涉及的机制,以及探索血管疾病的治疗策略,为再生医学提供新的思路。

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