sVEGFR1 Is Enriched in Hepatic Vein Blood-Evidence for a Provisional Hepatic Factor Candidate?
sVEGFR1 Is Enriched in Hepatic Vein Blood-Evidence for a Provisional Hepatic Factor Candidate?
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SVEGFR1富含肝静脉血液传播，成为临时肝脏因子候选者吗？
DOI：
10.3389/fped.2021.679572
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发表时间：
2021
影响因子：
2.6
通讯作者：
Ramchandran R
中科院分区：
文献类型：
--
作者：
Spearman AD;Gupta A;Pan AY;Gudausky TM;Foerster SR;Konduri GG;Ramchandran R
背景：肺动静脉畸形(PAVMs)是姑息性单室先天性心脏病的常见后遗症，其发病机制尚不清楚。在这项初步研究中，我们使用配对的患者血液样本来确定肝静脉血中浓缩的潜在肝因子候选。方法：采集40例0~10岁先天性单、双室先天性心脏病患儿的肝静脉(HV)和上腔静脉(SVC)静脉血。我们使用了三种独立的蛋白质分析来确定HV和SVC血液之间的蛋白质组学差异。随后，我们研究了我们的定量蛋白质差异与人肺微血管内皮细胞检测的相关性。结果：两个独立的蛋白质芯片(半定量免疫印迹和定量芯片)证实，与SVC血清相比，HV血清中可溶性血管内皮生长因子受体1(SVEGFR1)的表达显著升高。我们用ELISA法证实了先前的结果，即sVEGFR1在HV血清中富含(n=24，p<；0.0001)。最后，我们在体外研究了定量的HV和SVC血清中sVEGFR1的水平。在体外，与sVC水平相比，sVEGFR1HV水平降低了尖端细胞选择(p=0.0482)和管子形成(更少的管[p=0.0246]，更短的管长度[p=0.0300])。结论：基于一个小的异质性队列，与配对的SVC样本相比，HV血清中sVEGFR1的水平升高，并且这两个体静脉中sVEGFR1的平均浓度导致体外培养的肺内皮细胞表型的差异。需要进一步的研究来确定sVEGFR1是否在缓解性单室先天性心脏病患者的肺微血管重塑和PAVMS中起直接作用。
Background: Pulmonary arteriovenous malformations (PAVMs) are common sequelae of palliated univentricular congenital heart disease, yet their pathogenesis remain poorly defined. In this preliminary study, we used paired patient blood samples to identify potential hepatic factor candidates enriched in hepatic vein blood. Methods: Paired venous blood samples were collected from the hepatic vein (HV) and superior vena cava (SVC) from children 0 to 10 years with univentricular and biventricular congenital heart disease (n = 40). We used three independent protein analyses to identify proteomic differences between HV and SVC blood. Subsequently, we investigated the relevance of our quantified protein differences with human lung microvascular endothelial assays. Results: Two independent protein arrays (semi-quantitative immunoblot and quantitative array) identified that soluble vascular endothelial growth factor receptor 1 (sVEGFR1) is significantly elevated in HV serum compared to SVC serum. Using ELISA, we confirmed the previous findings that sVEGFR1 is enriched in HV serum (n = 24, p < 0.0001). Finally, we studied the quantified HV and SVC serum levels of sVEGFR1 in vitro. HV levels of sVEGFR1 decreased tip cell selection (p = 0.0482) and tube formation (fewer tubes [p = 0.0246], shorter tube length [p = 0.0300]) in vitro compared to SVC levels of sVEGFR1. Conclusions: Based on a small heterogenous cohort, sVEGFR1 is elevated in HV serum compared to paired SVC samples, and the mean sVEGFR1 concentrations in these two systemic veins cause pulmonary endothelial phenotypic differences in vitro. Further research is needed to determine whether sVEGFR1 has a direct role in pulmonary microvascular remodeling and PAVMs in patients with palliated univentricular congenital heart disease.
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影响因子：
9.8
作者：
Dallinga MG;Yetkin-Arik B;Kayser RP;Vogels IMC;Nowak-Sliwinska P;Griffioen AW;van Noorden CJF;Klaassen I;Schlingemann RO
通讯作者：
Schlingemann RO
影响因子：
9.8
作者：
Nowak-Sliwinska P;Alitalo K;Allen E;Anisimov A;Aplin AC;Auerbach R;Augustin HG;Bates DO;van Beijnum JR;Bender RHF;Bergers G;Bikfalvi A;Bischoff J;Böck BC;Brooks PC;Bussolino F;Cakir B;Carmeliet P;Castranova D;Cimpean AM;Cleaver O;Coukos G;Davis GE;De Palma M;Dimberg A;Dings RPM;Djonov V;Dudley AC;Dufton NP;Fendt SM;Ferrara N;Fruttiger M;Fukumura D;Ghesquière B;Gong Y;Griffin RJ;Harris AL;Hughes CCW;Hultgren NW;Iruela-Arispe ML;Irving M;Jain RK;Kalluri R;Kalucka J;Kerbel RS;Kitajewski J;Klaassen I;Kleinmann HK;Koolwijk P;Kuczynski E;Kwak BR;Marien K;Melero-Martin JM;Munn LL;Nicosia RF;Noel A;Nurro J;Olsson AK;Petrova TV;Pietras K;Pili R;Pollard JW;Post MJ;Quax PHA;Rabinovich GA;Raica M;Randi AM;Ribatti D;Ruegg C;Schlingemann RO;Schulte-Merker S;Smith LEH;Song JW;Stacker SA;Stalin J;Stratman AN;Van de Velde M;van Hinsbergh VWM;Vermeulen PB;Waltenberger J;Weinstein BM;Xin H;Yetkin-Arik B;Yla-Herttuala S;Yoder MC;Griffioen AW
通讯作者：
Griffioen AW
影响因子：
21.3
作者：
Jin Y;Muhl L;Burmakin M;Wang Y;Duchez AC;Betsholtz C;Arthur HM;Jakobsson L
通讯作者：
Jakobsson L
影响因子：
2.5
作者：
Spearman AD;Gupta A;Pan AY;Gronseth EI;Thirugnanam K;Gudausky TM;Foerster SR;Ramchandran R
通讯作者：
Ramchandran R
影响因子：
15.9
作者：
Maynard, SE;Min, JY;Karumanchi, SA
通讯作者：
Karumanchi, SA