Del Giacco Stefano R, Firinu Davide, Minciullo Paola Lucia, Barca Maria Pina, Manconi Paolo Emilio, Tartarisco Gennaro, Cristani Mariateresa, Saija Antonella, Gangemi Sebastiano
Department of Medical Sciences "M. Aresu", University of Cagliari, Cagliari, Italy.
School and Operative Unit of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
Arch Med Sci. 2019 Jan;15(1):92-98. doi: 10.5114/aoms.2017.66160. Epub 2017 Jul 31.
Hereditary angioedema due to C1-INH deficiency (C1-INH-HAE) or with normal C1-INH is characterized by recurrent swellings due to uncontrolled production of vasoactive mediators, among which bradykinin (BK) is crucial. Through the binding and activation of the two human BK-receptors, kinins may have dual beneficial and deleterious effects in vascular and inflammation physiopathology by inducing oxidative stress. We aimed to assess the serum concentrations of advanced glycation end products (AGEs) and advanced oxidation protein products (AOPPs) in patients affected by HAE.
Blood samples were collected to measure the serum concentrations of AGEs and AOPPs by spectrofluorimetric and spectrophotometric methods in patients affected by C1-INH-HAE and FXII-HAE during the remission state.
We showed that the circulating levels of AOPPs observed on control group (0.94 (0.36) nmol/mg) were significantly lower than those observed on the C1-INH-HAE group (1.68 (0.47) nmol/mg; = 0.002) and FXII-HAE (1.50 (0.27) nmol/mg; = 0.001). Moreover, the circulating levels of AGEs were significantly higher in C1-INH-HAE group (211.58 (151.05) AU/g; = 0.02) than the FXII group (141.48 (89.59) AU/g), thus demonstrating a state of heightened oxidative stress.
Our observations show additional underlying events involved in HAE and are of central importance for further investigations of differences in bradykinin receptors signaling among the two disease subgroups.
由于C1-INH缺乏引起的遗传性血管性水肿(C1-INH-HAE)或C1-INH正常的遗传性血管性水肿的特征是血管活性介质产生失控导致反复肿胀,其中缓激肽(BK)至关重要。通过两种人类BK受体的结合和激活,激肽可能通过诱导氧化应激在血管和炎症病理生理学中产生有益和有害的双重作用。我们旨在评估遗传性血管性水肿患者血清中晚期糖基化终产物(AGEs)和晚期氧化蛋白产物(AOPPs)的浓度。
采集血液样本,采用荧光分光光度法和分光光度法测定处于缓解状态的C1-INH-HAE和FXII-HAE患者血清中AGEs和AOPPs的浓度。
我们发现,对照组观察到的AOPPs循环水平(0.94(0.36)nmol/mg)显著低于C1-INH-HAE组(1.68(0.47)nmol/mg;P = 0.002)和FXII-HAE组(1.50(0.27)nmol/mg;P = 0.001)。此外,C1-INH-HAE组的AGEs循环水平(211.58(151.05)AU/g;P = 0.02)显著高于FXII组(141.48(89.59)AU/g),从而表明氧化应激增强状态。
我们的观察结果显示了遗传性血管性水肿中涉及的其他潜在事件,对于进一步研究两个疾病亚组之间缓激肽受体信号传导的差异至关重要。