Burtenshaw Denise, Kitching Michael, Redmond Eileen M, Megson Ian L, Cahill Paul A
Vascular Biology & Therapeutics, School of Biotechnology, Dublin City University, Dublin, Ireland.
School of Chemistry, Dublin City University, Dublin, Ireland.
Front Cardiovasc Med. 2019 Aug 2;6:89. doi: 10.3389/fcvm.2019.00089. eCollection 2019.
Arteriosclerosis causes significant morbidity and mortality worldwide. Central to this process is the development of subclinical non-atherosclerotic intimal lesions before the appearance of pathologic intimal thickening and advanced atherosclerotic plaques. Intimal thickening is associated with several risk factors, including oxidative stress due to reactive oxygen species (ROS), inflammatory cytokines and lipid. The main ROS producing systems are reduced nicotinamide dinucleotide phosphate (NADPH) oxidase (NOX). ROS effects are context specific. Exogenous ROS induces apoptosis and senescence, whereas intracellular ROS promotes stem cell differentiation, proliferation, and migration. Lineage tracing studies using murine models of subclinical atherosclerosis have revealed the contributory role of medial smooth muscle cells (SMCs), resident vascular stem cells, circulating bone-marrow progenitors and endothelial cells that undergo endothelial-mesenchymal-transition (EndMT). This review will address the putative physiological and patho-physiological roles of ROS in controlling vascular cell fate and ROS contribution to vascular regeneration and disease progression.
动脉硬化在全球范围内导致了严重的发病率和死亡率。这一过程的核心是在病理性内膜增厚和晚期动脉粥样硬化斑块出现之前，亚临床非动脉粥样硬化内膜病变的发展。内膜增厚与多种危险因素有关，包括活性氧（ROS）引起的氧化应激、炎性细胞因子和脂质。主要的ROS产生系统是还原型烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶（NOX）。ROS的作用具有背景特异性。外源性ROS诱导细胞凋亡和衰老，而细胞内ROS促进干细胞分化、增殖和迁移。使用亚临床动脉粥样硬化小鼠模型的谱系追踪研究揭示了中层平滑肌细胞（SMC）、驻留血管干细胞、循环骨髓祖细胞和经历内皮-间充质转化（EndMT）的内皮细胞的作用。本文将探讨ROS在控制血管细胞命运中的假定生理和病理生理作用，以及ROS对血管再生和疾病进展的影响。
