Vascular damage and lack of angiogenesis in systemic sclerosis skin
Vascular damage and lack of angiogenesis in systemic sclerosis skin
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DOI：
10.1007/s10067-003-0698-1
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发表时间：
2003-09-01
影响因子：
3.4
通讯作者：
Virtanen, I
中科院分区：
文献类型：
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作者：
Konttinen, YT;Mackiewicz, Z;Virtanen, I
本研究的目的是分析皮肤微血管损伤和代偿性血管生成系统性硬化症（SSc）患者与系统性红斑狼疮（SLE），雷诺现象（RP）和健康对照组相比。使用血管性血友病因子和β（3）整合素亚单位特异性抗体、TechMate免疫染色机器人和生物素-链霉亲和素方案，对皮肤活检（9例SSc、10例SLE、9例RP和12例健康对照）进行免疫组织化学。在SSc的早期阶段，vWF被发现在血管周围的空间和间质基质中的乳头状，但不是在网状真皮，特别是周围的小水肿血管的单核细胞浸润。SSc标本中vWF的血管外释放与相关内皮细胞内免疫反应性的弱或甚至完全缺乏相关。SSc的晚期特征为真皮乳头丢失、表皮下纤维化、血管生成不足和内皮vWF表达增强，无血管外渗漏。在所有研究的SSc患者中，只有少数血管的β（3）整合素亚基免疫染色较弱。这项工作表明，vWF不仅被释放到体循环，但也泄漏到血管周围空间/基质。局部vWF的释放和沉积可能是SSc发病机制中微血管受累的敏感和早期标志物。局部vWF释放可能在血小板粘附、聚集、血栓形成和真皮结缔组织重塑中起作用。尽管在SSc中进行了一些补偿性血管生成的尝试，如β（3）整联蛋白亚基表达所证明的，但很明显，血管生成反应不能阻止疾病晚期血管减少的发展。
The aim of this study was to analyse microvascular damage and compensatory angiogenesis in skin from patients with systemic sclerosis (SSc) compared with systemic lupus erythematosus (SLE), Raynaud's phenomenon (RP) and healthy controls. Immunohistochemistry was used for skin biopsies (9 SSc, 10 SLE, 9 RP and 12 healthy controls) using von Willebrand factor and beta(3) integrin subunit specific antibodies, TechMate immunostaining robot and biotin-streptavidin protocol. In the early stages of SSc, vWF was found in the perivascular space and interstitial matrix in papillary but not in the reticular dermis, in particular around small oedematous blood vessels infiltrated by mononuclear cells. The extravascular release of vWF in SSc specimens was associated with weak or even a total lack of immunoreactivity within the associated endothelial cells. Late stages of SSc were characterised by loss of the dermal papillae, subepidermal fibrosis, hypovascularity and strong endothelial vWF expression without extravascular leakage. In all SSc patients studied only a few vascular profiles were weakly immunostained for beta(3) integrin subunit. This work demonstrates that vWF is not only released into the systemic circulation, but is also leaked to the perivascular space/matrix. This local release and deposition of vWF is probably a sensitive and early marker of microvascular involvement in SSc pathogenesis. Local vWF release may play a role in platelet adhesion, aggregation, thrombogenesis and dermal connective tissue remodelling. In spite of some attempts towards compensatory angiogenesis in SSc, as evidenced by beta(3) integrin subunit expression, it was evident that the angiogenic response was not able to prevent the development of hypovascularity during the advanced stages of the disease.