Abdulle Amaal E, Diercks Gilles F H, Feelisch Martin, Mulder Douwe J, van Goor Harry
Department of Internal Medicine, Division of Vascular Medicine, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands.
Section Pathology, Department of Pathology and Medical Biology, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands.
Front Physiol. 2018 Aug 24;9:1177. doi: 10.3389/fphys.2018.01177. eCollection 2018.
Systemic sclerosis (SSc) is a rare connective tissue disease characterized by autoimmunity, vasculopathy, and progressive fibrosis typically affecting multiple organs including the skin. SSc often is a lethal disorder, because effective disease-modifying treatment still remains unavailable. Vasculopathy with endothelial dysfunction, perivascular infiltration of mononuclear cells, vascular wall remodeling and rarefaction of capillaries is the hallmark of the disease. Most patients present with vasospastic attacks of the digital arteries referred to as 'Raynaud's phenomenon,' which is often an indication of an underlying widespread vasculopathy. Although autoimmune responses and inflammation are both found to play an important role in the pathogenesis of this vasculopathy, no definite initiating factors have been identified. Recently, several studies have underlined the potential role of oxidative stress in the pathogenesis of SSc vasculopathy thereby proposing a new aspect in the pathogenesis of this disease. For instance, circulating levels of reactive oxygen species (ROS) related markers have been found to correlate with SSc vasculopathy, the formation of fibrosis and the production of autoantibodies. Excess ROS formation is well-known to lead to endothelial cell (EC) injury and vascular complications. Collectively, these findings suggest a potential role of ROS in the initiation and progression of SSc vasculopathy. In this review, we present the background of oxidative stress related processes (e.g., EC injury, autoimmunity, inflammation, and vascular wall remodeling) that may contribute to SSc vasculopathy. Finally, we describe the use of oxidative stress related read-outs as clinical biomarkers of disease activity and evaluate potential anti-oxidative strategies in SSc.
系统性硬化症（SSc）是一种罕见的结缔组织疾病，其特征为自身免疫、血管病变以及通常累及包括皮肤在内的多个器官的进行性纤维化。SSc往往是一种致命性疾病，因为目前仍没有有效的疾病改善治疗方法。血管病变伴内皮功能障碍、单核细胞血管周围浸润、血管壁重塑和毛细血管稀疏是该疾病的标志。大多数患者会出现指动脉血管痉挛发作，即所谓的“雷诺现象”，这通常是潜在广泛性血管病变的一个迹象。尽管自身免疫反应和炎症在这种血管病变的发病机制中都起着重要作用，但尚未确定明确的起始因素。最近，多项研究强调了氧化应激在SSc血管病变发病机制中的潜在作用，从而为该疾病的发病机制提出了一个新的方面。例如，已发现活性氧（ROS）相关标志物的循环水平与SSc血管病变、纤维化形成和自身抗体产生相关。众所周知，过量的ROS形成会导致内皮细胞（EC）损伤和血管并发症。总体而言，这些发现表明ROS在SSc血管病变的起始和进展中具有潜在作用。在本综述中，我们介绍了可能导致SSc血管病变的氧化应激相关过程（如EC损伤、自身免疫、炎症和血管壁重塑）的背景。最后，我们描述了将氧化应激相关指标用作疾病活动临床生物标志物的情况，并评估了SSc中潜在的抗氧化策略。
