Vancheeswaran R, Magoulas T, Efrat G, Wheeler-Jones C, Olsen I, Penny R, Black C M
Department of Rheumatology, Royal Free Hospital, London, UK.
J Rheumatol. 1994 Oct;21(10):1838-44.
To investigate the circulating levels of endothelin-1 (ET-1) in serum (sET-1) in patients with pulmonary disease [pulmonary fibrosis (PF) and pulmonary hypertension (PHT)], and renal involvement [hypertensive renal crisis (HRC)] in the 2 major subsets of systemic sclerosis (SSc) in order to determine the significance of sET-1 levels in relation to specific organ involvement or to the underlying pathogenic mechanisms of vascular damage and fibrosis.
In addition to the measurement of ET-1 in serum using a competitive radioimmunoassay, the circulating levels of angiotensin converting enzyme (ACE) and plasma von Willebrand factor (vWF) were measured as markers of endothelial damage in the various disease groups.
Levels of sET-1 were significantly increased in 64 patients with diffuse systemic sclerosis (dSSc) and 17 patients with primary Raynaud's phenomenon (RP) compared with 22 healthy individuals. sET-1 levels were equally elevated in diffuse cutaneous disease (dcSSc) with only fibrotic dermal or lung pathology compared with patients with additional PHT or HRC crisis. These observations were in marked contrast to the sET-1 levels seen in patients with the limited cutaneous form of SSc (lcSSc) where only patients with lcSSc with hypertensive lung or renal disease had significantly higher levels of sET-1 than comparable lcSSc patients with only fibrotic dermal and lung disease. sET-1 levels were additionally found to correlate with plasma vWF, skin fibrosis (skin score) and duration of disease in patients with SSc.
The presence of significantly raised sET-1 levels in patients with dcSSc with widespread fibrosis and patients with lcSSc with hypertensive disease and the relationship seen between sET-1 levels and markers of fibrosis and vascular damage suggest that ET-1 may be important in the pathogenesis of both the fibrotic and vascular manifestations in SSc.
研究系统性硬化症（SSc）两大主要亚组中肺部疾病[肺纤维化（PF）和肺动脉高压（PHT）]及肾脏受累[高血压肾危象（HRC）]患者血清中内皮素-1（ET-1）的循环水平，以确定sET-1水平与特定器官受累或血管损伤及纤维化潜在致病机制的关系。
除了使用竞争性放射免疫分析法测定血清中的ET-1外，还测定了各疾病组中血管紧张素转换酶（ACE）的循环水平和血浆血管性血友病因子（vWF）作为内皮损伤的标志物。
与22名健康个体相比，64例弥漫性系统性硬化症（dSSc）患者和17例原发性雷诺现象（RP）患者的sET-1水平显著升高。与合并PHT或HRC危象的患者相比，仅存在皮肤或肺部纤维化的弥漫性皮肤疾病（dcSSc）患者的sET-1水平同样升高。这些观察结果与局限性皮肤型SSc（lcSSc）患者的sET-1水平形成鲜明对比，在lcSSc患者中，只有合并高血压性肺部或肾脏疾病的lcSSc患者的sET-1水平显著高于仅患有皮肤和肺部纤维化的lcSSc患者。此外，还发现SSc患者的sET-1水平与血浆vWF、皮肤纤维化（皮肤评分）和病程相关。
广泛纤维化的dcSSc患者以及合并高血压疾病的lcSSc患者中sET-1水平显著升高，以及sET-1水平与纤维化和血管损伤标志物之间的关系表明，ET-1可能在SSc的纤维化和血管表现的发病机制中起重要作用。
