Research Laboratory, 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
J Clin Immunol. 2012 Feb;32(1):61-9. doi: 10.1007/s10875-011-9606-7. Epub 2011 Oct 19.
The bradykinin pathway in the pathomechanism of hereditary angioedema due to C1-inhibitor deficiency (henceforward "hereditary angioedema") has been thoroughly studied; however, much less is known about endothelial cell function. Enhanced endothelial cell permeability is obvious during edematous attacks, but not during inter-attack periods. Our knowledge about other endothelial characteristics is even more incomplete.
Therefore the aim of this study was to characterize endothelial cell function in hereditary angioedema patients during symptom-free, inter-attack periods.
We measured the serum levels of soluble E-selectin, endothelin-1, and von Willebrand factor along with collagen-binding activity in 49 hereditary angioedema patients and in 50 healthy controls.
Endothelin-1 and von Willebrand factor level, as well as its collagen-binding activity, were similar in hereditary angioedema patients and in controls; however, we found elevated soluble E-selectin levels in the patients. Interestingly, soluble E-selectin concentration did not correlate with any of the inflammatory markers or smoking, and it is not the consequence of the known E-selectin/C1-inhibitor interaction (an analytical phenomenon). In a multiple logistic regression model, the difference in soluble E-selectin between hereditary angioedema patients and controls remained highly significant when adjusted for age, gender, smoking, C-reactive protein, and AB0 blood groups.
These results demonstrate that in hereditary angioedema, the majority of endothelial functions are normal during inter-attack periods; however, soluble E-selectin levels are elevated. The higher soluble E-selectin plasma concentration is unlikely to result from inflammation; rather, it reflects enhanced shedding mechanisms.
在 C1 抑制剂缺乏引起的遗传性血管性水肿（以下简称“遗传性血管性水肿”）的发病机制中，激肽通路已得到深入研究；然而，内皮细胞功能的了解要少得多。在水肿发作期间，内皮细胞通透性明显增强，但在发作间期则不然。我们对其他内皮细胞特征的了解甚至更加不完整。
因此，本研究旨在描述无症性发作间期遗传性血管性水肿患者的内皮细胞功能。
我们测量了 49 例遗传性血管性水肿患者和 50 例健康对照者的血清可溶性 E-选择素、内皮素-1 和血管性血友病因子水平，以及胶原结合活性。
内皮素-1 和血管性血友病因子水平及其胶原结合活性在遗传性血管性水肿患者和对照组中相似；然而，我们发现患者的可溶性 E-选择素水平升高。有趣的是，可溶性 E-选择素浓度与任何炎症标志物或吸烟均无关，并且不是已知的 E-选择素/C1 抑制剂相互作用（分析现象）的结果。在多因素逻辑回归模型中，当调整年龄、性别、吸烟、C 反应蛋白和 AB0 血型后，遗传性血管性水肿患者与对照组之间可溶性 E-选择素的差异仍具有高度显著性。
这些结果表明，在遗传性血管性水肿中，发作间期大多数内皮功能正常；然而，可溶性 E-选择素水平升高。较高的可溶性 E-选择素血浆浓度不太可能是由炎症引起的；相反，它反映了增强的脱落机制。
