摘要
Background and Aims:The results of basic research implicate the vascular endothelial growth factor(VEGF)family as a potential target of hepatopulmonary syndrome(HPS).However,the negative results of anti-angiogenetic therapy in clinical studies have highlighted the need for markers for HPS.Therefore,we aimed to determine whether VEGF family members and their receptors can be potential biomarkers for HPS through clinical and experimental studies.Methods:Clinically,patients with chronic liver disease from two medical centers were enrolled and examined for HPS.Patients were divided into HPS,intrapulmonary vascular dilation[positive contrast-enhanced echocardiography(CEE)and normal oxygenation]and CEE-negative groups.Baseline information and perioperative clinical data were compared between HPS and non-HPS patients.Serum levels of VEGF family members and their receptors were measured.In parallel,HPS rats were established by common bile duct ligation.Liver,lung and serum samples were collected for the evaluation of pathophysiologic changes,as well as the expression levels of the above factors.Results:In HPS rats,all VEGF family members and their receptors underwent significant changes;however,only soluble VEGFR1(sFlt-1)and the sFlt-1/placental growth factor(PLGF)ratio were changed in almost the same manner as those in HPS patients.Furthermore,through feature selection and internal and external validation,sFlt-1 and the sFlt-1/PLGF ratio were identified as the most important variables to distinguish HPS from non-HPS patients.Conclusions:Our results from animal and human studies indicate that sFlt-1 and the sFlt-1/PLGF ratio in serum are potential markers for HPS.
基金
supported by National Science Foundation of China(No.82070630 from Bin Yi,82100658 from Yu-jie Li and 82170634 from Peng Li)
National Key R&D Program of China(No.2018YFC0116702 from Bin Yi)
Special support for Chongqing postdoctoral research project in 2020 from Yujie Li,Sichuan science and technology department research projects(2019YFS0221 from Peng Li)
Chongqing Science and health joint medical research project(2020FYYX076,from Bin Yi)
special support project for improving scientific and technological innovation ability of undergraduate(2021XBK19 from Xian-feng Wu).
