Department of Internal Medicine and Rheumatology, Kerckhoff Clinic, Justus-Liebig University Giessen, Benekestrasse 2-8, D-61231, Bad Nauheim, Germany.
Autoimmunity. 2009 Nov;42(7):587-95. doi: 10.1080/08916930903002487.
Although being classified as autoimmune connective tissue disease, dominant components of the pathophysiology of systemic sclerosis (SSc) consists of mechanisms of vascular damage, which can occur early in the course of the disease. Amongst them are abnormal vasoreactivity, hypoxia, insufficient neoangiogenesis and direct damage of vascular and perivascular cells. They result in a decreased capillary blood flow, and subsequently in clinically overt symptoms such as Raynaud's syndrome and fingertip ulcers. In addition, in active disease vascular pathology can affect various other organs, predominantly the lung, the kidney, the heart but also the gastrointestinal tract. Vascular pathology contributes also significantly to overall morbidity and mortality in SSc patients and reduces life expectancy by at least a decade. Fortunately, molecular biology has revealed a number of underlying pathways on the cellular and subcellular levels, including key factors of the aberrant function of (peri)vascular cells and autoimmune effector cells, the dysregulation of vasoconstrictive molecules and their receptors, the upregulation of intracellular signaling kinases and the altered balance of hypoxia-induced vascular growth factors. This increasing knowledge of vascular pathology in SSc has also resulted in novel therapeutic approaches ranging from endothelin antagonists to application of progenitor cells to counteract this aberrant vascular pathology and to support the repair of the dysfunctional vasculature.
虽然系统性硬化症 (SSc) 被归类为自身免疫性结缔组织疾病，但它的病理生理学的主要组成部分是血管损伤机制，这些机制可能在疾病早期就已经发生。其中包括血管反应异常、缺氧、新生血管形成不足以及血管和血管周围细胞的直接损伤。这些机制导致毛细血管血流减少，随后出现雷诺现象和指尖溃疡等临床明显症状。此外，在活动期，血管病变还会影响到其他各种器官，主要是肺、肾、心脏，也包括胃肠道。血管病变也显著导致 SSc 患者的总发病率和死亡率增加，并使预期寿命至少缩短十年。幸运的是，分子生物学已经揭示了细胞和亚细胞水平上的许多潜在途径，包括（血管周围）细胞和自身免疫效应细胞异常功能的关键因素、血管收缩分子及其受体的失调、细胞内信号转导激酶的上调以及缺氧诱导的血管生长因子平衡的改变。对 SSc 血管病理学的这一不断增加的认识也导致了新的治疗方法的出现，从内皮素拮抗剂到应用祖细胞来对抗这种异常的血管病理学并支持功能失调的血管的修复。
