Nox2 impairs VEGF-A-induced angiogenesis in placenta via mitochondrial ROS-STAT3 pathway.
Nox2 impairs VEGF-A-induced angiogenesis in placenta via mitochondrial ROS-STAT3 pathway.
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Nox 2通过线粒体ROS-STAT 3途径损害VEGF-A诱导的胎盘血管生成
DOI：
10.1016/j.redox.2021.102051
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发表时间：
2021-09
期刊：
影响因子：
11.4
通讯作者：
Tan C
中科院分区：
文献类型：
--
作者：
Hu C;Wu Z;Huang Z;Hao X;Wang S;Deng J;Yin Y;Tan C
胎盘血管生成异常与胎儿宫内生长受限（IUGR）有关，但胎盘血管生成异常的机制仍不清楚。低出生体重（LBW）胎儿胎盘血管密度较低，NADPH氧化酶2 （Nox2）表达较高，且Nox2与胎盘血管密度呈负相关。此外，该研究首次揭示了Nox2缺乏在体外和体内促进血管生成，血管内皮生长因子- a （VEGF-A）在Nox2控制的猪血管内皮细胞（PVECs）血管生成抑制中起重要作用。在机制上，Nox2通过诱导线粒体活性氧（ROS）的产生来抑制细胞核内磷酸化信号转导和转录激活因子3 （p-STAT3）。双荧光素酶测定证实，Nox2的敲低以STAT3依赖的方式降低VEGF-A的表达。我们的研究结果表明，Nox2是通过增加VEGF-A表达促进血管生成的潜在治疗靶点，并可作为IUGR胎儿的预后指标。
Aberrant placental angiogenesis is associated with fetal intrauterine growth restriction (IUGR), but the mechanism underlying abnormal placental angiogenesis remains largely unknown. Here, lower vessel density and higher expression of NADPH oxidases 2 (Nox2) were observed in the placentae for low birth weight (LBW) fetuses versus normal birth weight (NBW) fetuses, with a negative correlation between Nox2 and placental vessel density. Moreover, it was revealed for the first time that Nox2 deficiency facilitates angiogenesis in vitro and in vivo, and vascular endothelial growth factor-A (VEGF-A) has an essential role in Nox2-controlled inhibition of angiogenesis in porcine vascular endothelial cells (PVECs). Mechanistically, Nox2 inhibited phospho-signal transducer and activator of transcription 3 (p-STAT3) in the nucleus by inducing the production of mitochondrial reactive oxygen species (ROS). Dual-luciferase assay confirmed that knockdown of Nox2 reduces the expression of VEGF-A in an STAT3 dependent manner. Our results indicate that Nox2 is a potential target for therapy by increasing VEGF-A expression to promote angiogenesis and serves as a prognostic indicator for fetus with IUGR.
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影响因子：
7.4
作者：
Osborn-Heaford HL;Murthy S;Gu L;Larson-Casey JL;Ryan AJ;Shi L;Glogauer M;Neighbors JD;Hohl R;Carter AB
通讯作者：
Carter AB
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
NADPH 氧化酶触发的骨-种植体界面氧化应激导致血管生成受损：糖尿病高血糖条件下种植体失败的关键机制和治疗靶点
影响因子：
9.7
作者：
Hu, Xiao-Fan;Wang, Lin;Feng, Ya-Fei
通讯作者：
Feng, Ya-Fei
DOI：
10.1186/s13046-020-01621-y
发表时间：
2020-06-23
影响因子：
11.3
作者：
Cao, Ya;Wang, Jinglong;Fu, Guo-Hui
通讯作者：
Fu, Guo-Hui
影响因子：
16.6
作者：
Henriquez-Olguin, Carlos;Knudsen, Jonas R.;Jensen, Thomas E.
通讯作者：
Jensen, Thomas E.