Kanter Jenny E, Hsu Cheng-Chieh, Bornfeldt Karin E
Department of Medicine, University of Washington Medicine Diabetes Institute, University of Washington School of Medicine, Seattle, WA, United States.
Department of Pathology, University of Washington Medicine Diabetes Institute, University of Washington School of Medicine, Seattle, WA, United States.
Front Cardiovasc Med. 2020 Feb 14;7:10. doi: 10.3389/fcvm.2020.00010. eCollection 2020.
With the increasing prevalence of diabetes worldwide, vascular complications of diabetes are also on the rise. Diabetes results in an increased risk of macrovascular complications, with atherosclerotic cardiovascular disease (CVD) being the leading cause of death in adults with diabetes. The exact mechanisms for how diabetes promotes CVD risk are still unclear, although it is evident that monocytes and macrophages are key players in all stages of atherosclerosis both in the absence and presence of diabetes, and that phenotypes of these cells are altered by the diabetic environment. Evidence suggests that at least five pro-atherogenic mechanisms involving monocytes and macrophages contribute to the accelerated atherosclerotic lesion progression and hampered lesion regression associated with diabetes. These changes include (1) increased monocyte recruitment to lesions; (2) increased inflammatory activation; (3) altered macrophage lipid accumulation and metabolism; (4) increased macrophage cell death; and (5) reduced efferocytosis. Monocyte and macrophage phenotypes and mechanisms have been revealed mostly by different animal models of diabetes. The roles of specific changes in monocytes and macrophages in humans with diabetes remain largely unknown. There is an ongoing debate on whether the changes in monocytes and macrophages are caused by altered glucose levels, insulin deficiency or insulin resistance, lipid abnormalities, or combinations of these factors. Current research in humans and mouse models suggests that reduced clearance of triglyceride-rich lipoproteins and their remnants is one important mechanism whereby diabetes adversely affects macrophages and promotes atherosclerosis and CVD risk. Although monocytes and macrophages readily respond to the diabetic environment and can be seen as protagonists in diabetes-accelerated atherosclerosis, they are likely not instigators of the increased CVD risk.
随着全球糖尿病患病率的不断上升，糖尿病的血管并发症也在增加。糖尿病会增加大血管并发症的风险，动脉粥样硬化性心血管疾病（CVD）是糖尿病成年人死亡的主要原因。尽管很明显，无论是否存在糖尿病，单核细胞和巨噬细胞在动脉粥样硬化的各个阶段都是关键参与者，并且这些细胞的表型会因糖尿病环境而改变，但糖尿病如何促进心血管疾病风险的确切机制仍不清楚。有证据表明，至少有五种涉及单核细胞和巨噬细胞的促动脉粥样硬化机制导致了与糖尿病相关的动脉粥样硬化病变进展加速和病变消退受阻。这些变化包括：（1）单核细胞向病变部位的募集增加；（2）炎症激活增加；（3）巨噬细胞脂质蓄积和代谢改变；（4）巨噬细胞死亡增加；（5）吞噬作用降低。单核细胞和巨噬细胞的表型及机制大多是通过不同的糖尿病动物模型揭示的。在糖尿病患者中，单核细胞和巨噬细胞的特定变化所起的作用在很大程度上仍不清楚。关于单核细胞和巨噬细胞的变化是由血糖水平改变、胰岛素缺乏或胰岛素抵抗、脂质异常，还是这些因素的组合引起的，目前仍存在争议。目前在人类和小鼠模型中的研究表明，富含甘油三酯的脂蛋白及其残粒清除减少是糖尿病对巨噬细胞产生不利影响并促进动脉粥样硬化和心血管疾病风险的一个重要机制。尽管单核细胞和巨噬细胞很容易对糖尿病环境做出反应，并且可以被视为糖尿病加速动脉粥样硬化的主要因素，但它们可能不是心血管疾病风险增加的煽动者。
