METHODS: Here, we analyzed plasma levels of PLC, DAGs, and eCBs in 40 patients with FXII-HAE and 40 sex- and age-matched healthy individuals.
RESULTS: Plasma PLC activity was increased in FXII-HAE patients compared to controls. Concentrations of DAG 18:1-20:4, a lipid second messenger produced by PLC, were higher in FXII-HAE compared to controls, and positively correlated with PLC activity and cleaved high molecular kininogen (cHK). Also the concentrations of the DAG metabolite, 2-AG were altered in FXII-HAE. AEA and OEA were decreased in FXII-HAE patients compared to controls; by contrast, PEA, was increased. The levels of all tested mediators did not differ between symptomatic and asymptomatic patients. Moreover, C1INH-HAE patients had elevated plasma levels of PLC, which correlated with cHK, but the levels of DAGs and eCBs were the same as controls.
CONCLUSIONS: BK overproduction and BKR2 activation are linked to alteration of PLCs and their metabolites in patients with FXII-HAE. Our results may pave way to investigations on the functions of these mediators in the pathophysiology of FXII-HAE, and provide new potential biomarkers and therapeutic targets.
方法:这里,我们分析了PLC的血浆水平,DAG,和eCBs在40名FXII-HAE患者和40名性别和年龄匹配的健康个体中。
结果:与对照组相比,FXII-HAE患者的血浆PLC活性增加。由PLC产生的脂质第二信使DAG18:1-20:4的浓度,与对照组相比,FXII-HAE中的含量更高,与PLC活性和裂解的高分子激肽原(cHK)呈正相关。还有DAG代谢物的浓度,2-AG在FXII-HAE中改变。与对照组相比,FXII-HAE患者的AEA和OEA降低;相比之下,PEA,增加了。所有测试介质的水平在有症状和无症状患者之间没有差异。此外,C1INH-HAE患者的血浆PLC水平升高,与cHK相关,但DAG和eCBs的水平与对照组相同。
结论:BK过度产生和BKR2激活与FXII-HAE患者PLC及其代谢产物的改变有关。我们的结果可能为研究这些介质在FXII-HAE病理生理学中的功能铺平道路,并提供新的潜在生物标志物和治疗靶点。