Sakly N, Mirshahi P, Ducros E, Soria J, Ghedira I, Mirshahi M
Faculty of Pharmacy, Research Unit 03/UR/07-2, Monastir 5000, Tunisia; Faculty of Medicine, UMRS 872, CRC, Paris VI 15 rue de l'Ecole de Médecine, 75006 Paris, France.
Lupus. 2009 Jul;18(8):705-12. doi: 10.1177/0961203309103087.
Angiogenesis plays a critical role in the pathogenesis of several connective tissue diseases. There is, however, relatively little information available on the role of angiogenesis in systemic lupus erythematosus (SLE). The aim of this study was to investigate the angiogenic activity in sera of patients with SLE and to determine the association between angiogenic activity and clinical complications. Sera from 66 Tunisian females with SLE and from 32 healthy blood donors were studied for their angiogenic activity using the in-vitro tube formation test on Matrigel. Samples were divided into five groups according to their angiogenic activity, which was scored from 0 (no angiogenesis) to 4 (high angiogenic activity). Samples from each group were then tested randomly to assess serum concentration of vascular endothelial growth factor (VEGF). No correlation was found between angiogenic activity scores and serum VEGF levels. Considering angiogenesis assessment in-vitro, sera of patients with SLE showed a much higher angiogenic activity than healthy controls since a high angiogenic score (score 4) is present in 43.9% of patients and in 6.3% of controls (P < 0.0002). This high angiogenic activity is not correlated with disease activity; however, SLE patients with anti-dsDNA antibodies and those with nephritis showed higher angiogenic activity compared with patients without these complications since score 4 is found in 50.9% and 67.9% versus 9.1% (P = 0.017) and 26.3% (P < 0.001), respectively. In conclusion, our study showed that high serum angiogenic activity in SLE was not correlated with the VEGF levels. We suggest the use of the 'in-vitro' tube formation test as a better tool to study the angiogenic potential of sera. We found that in patients with SLE, serum angiogenic activity is increased compared with healthy controls. This high angiogenic activity is associated with renal complications and with the presence of anti-dsDNA antibodies. These findings suggest an involvement of angiogenesis disturbance in the pathogenesis of SLE.
血管生成在几种结缔组织疾病的发病机制中起着关键作用。然而,关于血管生成在系统性红斑狼疮(SLE)中的作用,现有信息相对较少。本研究的目的是调查SLE患者血清中的血管生成活性,并确定血管生成活性与临床并发症之间的关联。使用基质胶上的体外管形成试验,对66名突尼斯女性SLE患者和32名健康献血者的血清进行了血管生成活性研究。样本根据其血管生成活性分为五组,血管生成活性评分从0(无血管生成)到4(高血管生成活性)。然后对每组样本进行随机测试,以评估血管内皮生长因子(VEGF)的血清浓度。血管生成活性评分与血清VEGF水平之间未发现相关性。考虑到体外血管生成评估,SLE患者的血清显示出比健康对照高得多的血管生成活性,因为43.9%的患者存在高血管生成评分(4分),而对照组为6.3%(P < 0.0002)。这种高血管生成活性与疾病活动无关;然而,与没有这些并发症的患者相比,抗双链DNA抗体阳性的SLE患者和肾炎患者显示出更高的血管生成活性,因为4分分别出现在50.9%和67.9%的患者中,而无并发症患者为9.1%(P = 0.017)和26.3%(P < 0.001)。总之,我们的研究表明,SLE患者血清中高血管生成活性与VEGF水平无关。我们建议使用“体外”管形成试验作为研究血清血管生成潜力的更好工具。我们发现,与健康对照相比,SLE患者的血清血管生成活性增加。这种高血管生成活性与肾脏并发症和抗双链DNA抗体的存在有关。这些发现表明血管生成紊乱参与了SLE的发病机制。