Del Papa Nicoletta, Pignataro Francesca
Department of Rheumatology, ASST G. Pini-CTO, Milano, Italy.
Front Immunol. 2018 Jun 18;9:1383. doi: 10.3389/fimmu.2018.01383. eCollection 2018.
Systemic sclerosis (SSc) is a connective tissue disease characterized by a complex pathological process where the main scenario is represented by progressive loss of microvascular bed, with the consequent progressive fibrotic changes in involved organ and tissues. Although most aspects of vascular injury in scleroderma are poorly understood, recent data suggest that the scleroderma impairment of neovascularization could be related to both angiogenesis and vasculogenesis failure. Particularly, compensatory angiogenesis does not occur normally in spite of an important increase in many angiogenic factors either in SSc skin or serum. Besides insufficient angiogenesis, the contribution of defective vasculogenesis to SSc vasculopathy has been extensively studied. Over the last decades, our understanding of the processes responsible for the formation of new vessels after tissue ischemia has increased. In the past, adult neovascularization was thought to depend mainly on angiogenesis (a process by which new vessels are formed by the proliferation and migration of mature endothelial cells). More recently, increased evidence suggests that stem cells mobilize from the bone marrow into the peripheral blood (PB), differentiate in circulating endothelial progenitors (EPCs), and home to site of ischemia to contribute to vessel formation. Significant advances have been made in understanding the biology of EPCs, and molecular mechanisms regulating EPC function. Autologous EPCs now are becoming a novel treatment option for therapeutic vascularization and vascular repair, mainly in ischemic diseases. However, different diseases, such as cardiovascular diseases, diabetes, and peripheral artery ischemia are related to EPC dysfunction. Several studies have shown that EPCs can be detected in the PB of patients with SSc and are impaired in their function. Based on an online literature search (PubMed, EMBASE, and Web of Science, last updated December 2017) using keywords related to "endothelial progenitor cells" and "Systemic Sclerosis," "scleroderma vasculopathy," "angiogenesis," "vasculogenesis," this review gives an overview on the large body of data of current research in this issue, including controversies over the identity and functions of EPCs, their meaning as biomarker of SSc microangiopathy and their clinical potency.
系统性硬化症（SSc）是一种结缔组织疾病，其特征在于复杂的病理过程，主要表现为微血管床逐渐丧失，进而导致受累器官和组织发生进行性纤维化改变。尽管硬皮病中血管损伤的大多数方面仍知之甚少，但最近的数据表明，硬皮病中新血管形成受损可能与血管生成和血管发生失败均有关。特别是，尽管SSc皮肤或血清中许多血管生成因子显著增加，但代偿性血管生成并未正常发生。除了血管生成不足外，有缺陷的血管发生对SSc血管病变的作用也得到了广泛研究。在过去几十年中，我们对组织缺血后新血管形成过程的认识有所增加。过去，成人新血管形成主要被认为依赖于血管生成（一个由成熟内皮细胞增殖和迁移形成新血管的过程）。最近，越来越多的证据表明，干细胞从骨髓动员到外周血（PB），分化为循环内皮祖细胞（EPC），并归巢到缺血部位以促进血管形成。在理解EPC生物学以及调节EPC功能的分子机制方面已经取得了重大进展。自体EPC现在正成为治疗性血管生成和血管修复的一种新的治疗选择，主要用于缺血性疾病。然而，不同的疾病，如心血管疾病、糖尿病和外周动脉缺血都与EPC功能障碍有关。几项研究表明，SSc患者的PB中可检测到EPC，但其功能受损。基于使用与“内皮祖细胞”和“系统性硬化症”、“硬皮病血管病变”、“血管生成”、“血管发生”相关的关键词进行的在线文献检索（PubMed、EMBASE和Web of Science，最后更新于2017年12月），本综述概述了该问题当前研究的大量数据，包括关于EPC的身份和功能的争议、它们作为SSc微血管病生物标志物的意义及其临床潜力。
