Division of Vascular Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of General Surgery, Hangzhou First People's Hospital Affiliated to Nanjing Medical University, Hangzhou, China.
Biomed Res Int. 2018 May 23;2018:4019814. doi: 10.1155/2018/4019814. eCollection 2018.
Atherosclerosis is considered as a multifactorial disease in terms of the pathogenic mechanisms. Oxidative stress has been implicated in atherogenesis, and the putative mechanisms of its action include oxidative modification of redox-sensitive signaling factors. High mobility group box 1 (HMGB1) is a key inflammatory mediator in atherosclerosis, but if oxidized it loses its activity. Thus, whether and how it participates in oxidative stress-induced atherosclerosis are not clear. The current study found that exogenous HMGB1 dose-dependently inhibited the proliferation of multipotent vascular stem cells and their differentiation to smooth muscle cells induced by platelet-derived growth factor. But oxidative modification impaired the activity of HMGB1 to produce the effect. The stem cells were regarded as the source of smooth muscle cells in vascular remodeling and neointimal hyperplasia. Therefore, the findings suggested that HMGB1 participated in oxidative stress-induced atherosclerosis presumably by targeting multipotent vascular stem cells.
动脉粥样硬化被认为是一种多因素疾病，其发病机制涉及多个方面。氧化应激与动脉粥样硬化的发生有关，其作用的潜在机制包括氧化修饰易受氧化还原信号因子的影响。高迁移率族蛋白 B1（HMGB1）是动脉粥样硬化中的一种关键炎症介质，但如果发生氧化，其活性就会丧失。因此，它是否以及如何参与氧化应激诱导的动脉粥样硬化尚不清楚。本研究发现，外源性 HMGB1 可剂量依赖性地抑制血小板衍生生长因子诱导的多能血管干细胞增殖及其向平滑肌细胞的分化。但氧化修饰会损害 HMGB1 的活性，从而产生这种作用。干细胞被认为是血管重塑和新生内膜增生中平滑肌细胞的来源。因此，这些发现表明，HMGB1 可能通过靶向多能血管干细胞参与氧化应激诱导的动脉粥样硬化。
