Mechanisms of vascular damage in SScimplications for vascular treatment strategies
Mechanisms of vascular damage in SScimplications for vascular treatment strategies
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DOI：
10.1093/rheumatology/ken267
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发表时间：
2008-10-01
期刊：
影响因子：
5.5
通讯作者：
Matucci-Cerinic, M.
中科院分区：
文献类型：
--
作者：
Guiducci, S.;Distler, O.;Matucci-Cerinic, M.
血管异常是SSc的主要组成部分，但对引发血管损伤并阻止其修复的事件或机制知之甚少。在SSc中，尽管大量促血管生成因子（如VEGF）的表达增加，但血管生成不完全或缺乏。关于血管发生和循环内皮祖细胞在SSc中的存在和作用，最近发表了相互矛盾的结果。这些内皮祖细胞是内皮疾病的标志还是血管修复不足的原因还有待确定。人间充质干细胞（MSCs）可能是内皮祖细胞的替代来源，并且已经观察到内皮样MSCs的血管生成潜力降低。血管损伤的其他机制包括氧化应激和活化血小板释放的因子。此外，ET-1、PDGF等生长因子诱导血管平滑肌细胞增殖，导致内膜增厚。对于新的治疗策略的发展，重要的是要认识到不同的血管病理，一方面是毛细血管的非代偿性损失，另一方面是增生性血管病变的血管重塑，可能需要不同的治疗方法。
Vascular abnormalities are a major component of SSc, but little is known about the events or mechanisms that initiate vascular injury and prevent its repair. In SSc, angiogenesis is incomplete or lacking despite the increased expression of a large array of pro-angiogenic factors such as VEGF. Conflicting results have recently been published concerning the presence and role of vasculogenesis and circulating endothelial progenitor cells in SSc. It remains to be established if these endothelial progenitor cells are a marker of endothelial disease or a cause of insufficient vascular repair. Human mesenchymal stem cells (MSCs) may be an alternative source for endothelial progenitor cells, and it has been observed that the angiogenic potential of endothelial-like MSCs is reduced. Other mechanisms of vascular damage include oxidative stress and factors released from activated platelets. In addition, growth factors such as ET-1 and PDGF induce proliferation of vascular smooth muscle cells resulting in intimal thickening. For the development of new therapeutic strategies, it is important to realize that the different vascular pathologiesuncompensated loss of capillaries on one hand and vascular remodelling with a proliferative vasculopathy on the othermight require different treatment approaches.