Human epicardial cell-conditioned medium contains HGF/IgG complexes that phosphorylate RYK and protect against vascular injury.
Human epicardial cell-conditioned medium contains HGF/IgG complexes that phosphorylate RYK and protect against vascular injury.
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人心外膜细胞条件培养基含有 HGF/IgG 复合物，可磷酸化 RYK 并防止血管损伤。
DOI：
10.1093/cvr/cvv168
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发表时间：
2015
影响因子：
10.8
通讯作者：
Spees,JeffreyL
中科院分区：
文献类型：
--
作者：
Rao,KrithikaS;Aronshtam,Alexander;McElory-Yaggy,KearaL;Bakondi,Benjamin;VanBuren,Peter;Sobel,BurtonE;Spees,JeffreyL
AimsThe aim of this study was to evaluate the paracrine activity of human epicardial-derived cells (hEPDCs) to screen for secreted vasoprotective factors and develop therapeutics to treat vascular reperfusion injury.Methods and resultsEpicardial cells support cardiac development, repair, and remodelling after injury in part, through paracrine activity. We hypothesized that secreted ligands from hEPDCs would protect vascular integrity after myocardial infarction (MI) with reperfusion. During simulated ischaemia in culture (24–48 h), concentrated hEPDC-conditioned medium (EPI CdM) increased survival of primary cardiac endothelial cells. In a rat MI model, EPI CdM treatment reduced vascular injuryin vivoafter reperfusion. By phospho-receptor tyrosine kinase (RTK) arrays, ELISA, and neutralizing antibody screens, we identified hepatocyte growth factor (HGF) as a key vasoprotective factor in EPI CdM. Unexpectedly, we observed that some of the HGF in EPI CdM formed complexes with polyclonal IgG. Following reperfusion, preparations of HGF/IgG complexes provided greater vascular protection than free HGF with IgG. HGF/IgG complexes localized to blood vesselsin vivoand increased HGF retention time after administration. In subsequent screens, we found that ‘related to tyrosine kinase’ (RYK) receptor was phosphorylated after exposure of cardiac endothelial cells to HGF/IgG complexes, but not to free HGF with IgG. The enhanced protection conferred by HGF/IgG complexes was lost after antibody blockade of RYK. Notably, the HGF/IgG complex is the first ‘ligand’ shown to promote phosphorylation of RYK.ConclusionEarly treatment with HGF/IgG complexes after myocardial ischaemia with reperfusion may rescue tissue through vasoprotection conferred by c-Met and RYK signalling.
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DOI：
10.1002/ar.a.20398
发表时间：
2006-12-01
期刊：
ANATOMICAL RECORD PART A-DISCOVERIES IN MOLECULAR CELLULAR AND EVOLUTIONARY BIOLOGY
影响因子：
--
作者：
Eralp, Ismail;Lie-Venema, Heleen;Gittenberger-De Groot, Adriana C.
通讯作者：
Gittenberger-De Groot, Adriana C.
DOI：
10.1387/ijdb.12533024
发表时间：
2002-12
期刊：
The International journal of developmental biology
影响因子：
--
作者：
J. Pérez-Pomares;R. Carmona;M. González-Iriarte;Gerardo Atencia;A. Wessels;R. Muñoz-Chápuli
通讯作者：
J. Pérez-Pomares;R. Carmona;M. González-Iriarte;Gerardo Atencia;A. Wessels;R. Muñoz-Chápuli
影响因子：
20.1
作者：
EID, H;LARSON, DM;KELLY, RA
通讯作者：
KELLY, RA
影响因子：
37.8
作者：
Nagaya, N;Kangawa, K;Kitamura, S
通讯作者：
Kitamura, S
影响因子：
56.9
作者：
Bergmann;K. Fox;M. Ter-pogossian;B. Sobel;D. Collen
通讯作者：
Bergmann;K. Fox;M. Ter-pogossian;B. Sobel;D. Collen