Genomes and Genes
vascular endothelial growth factor receptor 1
Summary: A 180-kDa VEGF receptor found primarily in endothelial cells that is essential for vasculogenesis and vascular maintenance. It is also known as Flt-1 (fms-like tyrosine kinase receptor-1). A soluble, alternatively spliced isoform of the receptor may serve as a binding protein that regulates the availability of various ligands for VEGF receptor binding and signal transduction.
- Leppänen V, Prota A, Jeltsch M, Anisimov A, Kalkkinen N, Strandin T, et al. Structural determinants of growth factor binding and specificity by VEGF receptor 2. Proc Natl Acad Sci U S A. 2010;107:2425-30 pubmed publisher..Our results provide significant insights into the structural features that determine the high affinity and specificity of VEGF/VEGFR interactions. ..
- Al Ani B, Hewett P, Cudmore M, Fujisawa T, Saifeddine M, Williams H, et al. Activation of proteinase-activated receptor 2 stimulates soluble vascular endothelial growth factor receptor 1 release via epidermal growth factor receptor transactivation in endothelial cells. Hypertension. 2010;55:689-97 pubmed publisher
- Jacobsen K, Al Aql Z, Wan C, Fitch J, Stapleton S, Mason Z, et al. Bone formation during distraction osteogenesis is dependent on both VEGFR1 and VEGFR2 signaling. J Bone Miner Res. 2008;23:596-609 pubmed publisher..Both VEGFR1 and VEGFR2 are functionally essential in blood vessel and bone formation during DO and are needed to promote osteogenic over chondrogenic lineage progression. ..
- Ponticelli S, Marasco D, Tarallo V, Albuquerque R, Mitola S, Takeda A, et al. Modulation of angiogenesis by a tetrameric tripeptide that antagonizes vascular endothelial growth factor receptor 1. J Biol Chem. 2008;283:34250-9 pubmed publisher..This tetrameric tripeptide represents a new, promising compound for therapeutic approaches in pathologies where Flt-1 activation plays a crucial role. ..
- Hagberg C, Falkevall A, Wang X, Larsson E, Huusko J, Nilsson I, et al. Vascular endothelial growth factor B controls endothelial fatty acid uptake. Nature. 2010;464:917-21 pubmed publisher..The involvement of VEGF-B in lipid uptake may open up the possibility for novel strategies to modulate pathological lipid accumulation in diabetes, obesity and cardiovascular diseases. ..
- Heydarian M, McCaffrey T, Florea L, Yang Z, Ross M, Zhou W, et al. Novel splice variants of sFlt1 are upregulated in preeclampsia. Placenta. 2009;30:250-5 pubmed publisher..These findings provide evidence that human placenta expresses a family of sFlt1 splice variants, at least three of which are expressed as proteins, and which appear to be globally upregulated in preeclampsia. ..
- Sachanonta N, Medana I, Roberts R, Jones M, Day N, White N, et al. Host vascular endothelial growth factor is trophic for Plasmodium falciparum-infected red blood cells. Asian Pac J Allergy Immunol. 2008;26:37-45 pubmed..We conclude that P. falciparum iRBC can bind host VEGF-R on the erythrocyte membrane and accumulate host VEGF within the parasitophorous vacuole, which may have a trophic effect on parasite growth. ..
- Yoo S, Yoon H, Kim H, Chae C, De Falco S, Cho C, et al. Role of placenta growth factor and its receptor flt-1 in rheumatoid inflammation: a link between angiogenesis and inflammation. Arthritis Rheum. 2009;60:345-54 pubmed publisher..The use of the novel anti-flt-1 peptide, GNQWFI, may be an effective strategy for the treatment of RA. ..
- Zhang Z, Neiva K, Lingen M, Ellis L, Nor J. VEGF-dependent tumor angiogenesis requires inverse and reciprocal regulation of VEGFR1 and VEGFR2. Cell Death Differ. 2010;17:499-512 pubmed publisher..Collectively, this work demonstrates that VEGF-induced angiogenesis requires inverse regulation of VEGFR1 and VEGFR2 in tumor-associated endothelial cells. ..
- Chappell J, Taylor S, Ferrara N, Bautch V. Local guidance of emerging vessel sprouts requires soluble Flt-1. Dev Cell. 2009;17:377-86 pubmed publisher..Local sprout guidance defects are predicted to contribute to vessel dysmorphogenesis during perturbed development and disease. ..
- Fujita K, Nakayama M, Nakai Y, Takayama H, Nishimura K, Ujike T, et al. Vascular endothelial growth factor receptor 1 expression in pelvic lymph nodes predicts the risk of cancer progression after radical prostatectomy. Cancer Sci. 2009;100:1047-50 pubmed publisher..Although larger validation studies are required, our results suggest that VEGFR1 expression in pelvic lymph nodes predicts the risk of biochemical PSA recurrence after radical prostatectomy. ..
- Diab A, El Behery M, Ebrahiem M, Shehata A. Angiogenic factors for the prediction of pre-eclampsia in women with abnormal midtrimester uterine artery Doppler velocimetry. Int J Gynaecol Obstet. 2008;102:146-51 pubmed publisher..Measuring uterine perfusion and angiogenic factors concurrently in the second trimester improved the prediction of pre-eclampsia and IUGR. ..
- Mittar S, Ulyatt C, Howell G, Bruns A, Zachary I, Walker J, et al. VEGFR1 receptor tyrosine kinase localization to the Golgi apparatus is calcium-dependent. Exp Cell Res. 2009;315:877-89 pubmed publisherb>Vascular endothelial growth factor receptor 1 (VEGFR1) is an essential receptor tyrosine kinase that regulates mammalian vascular development and embryogenesis but its function is not well understood...
- Fischer C, Mazzone M, Jonckx B, Carmeliet P. FLT1 and its ligands VEGFB and PlGF: drug targets for anti-angiogenic therapy?. Nat Rev Cancer. 2008;8:942-56 pubmed publisher..Hopefully, other agents with complementary mechanisms, such as those that target placental growth factor, will offer novel opportunities for improved treatment. ..
- Avouac J, Wipff J, Goldman O, Ruiz B, Couraud P, Chiocchia G, et al. Angiogenesis in systemic sclerosis: impaired expression of vascular endothelial growth factor receptor 1 in endothelial progenitor-derived cells under hypoxic conditions. Arthritis Rheum. 2008;58:3550-61 pubmed publisher..5 pg/ml; P = 0.0042). These abnormalities did not seem to be related to genomic background. Our findings shed new light on the possible role of VEGFR-1 in the main vascular disturbances that occur in SSc and lead to more severe disease. ..
- Sivanandam V, Stephen S, Hernandez Alcoceba R, Alzuguren P, Zabala M, Van Rooijen N, et al. Lethality in an anti-angiogenic tumor gene therapy model upon constitutive but not inducible expression of the soluble vascular endothelial growth factor receptor 1. J Gene Med. 2008;10:1083-91 pubmed publisher
- Gould P, Gu M, Liao J, Ahmad S, Cudmore M, Ahmed A, et al. Upregulation of urotensin II receptor in preeclampsia causes in vitro placental release of soluble vascular endothelial growth factor receptor 1 in hypoxia. Hypertension. 2010;56:172-8 pubmed publisher..The increase in levels of soluble vascular endothelial growth factor receptor 1, an antiangiogenic agent known to inhibit placental vascularization, is an important cellular ..
- Roskoski R. VEGF receptor protein-tyrosine kinases: structure and regulation. Biochem Biophys Res Commun. 2008;375:287-91 pubmed publisher..Interaction between VEGFR1 and VEGFR2 or VEGFR2 and VEGFR3 alters receptor tyrosine phosphorylation. ..
- Jaroszewicz J, Januszkiewicz M, Flisiak R, Rogalska M, Kalinowska A, Wierzbicka I. Circulating vascular endothelial growth factor and its soluble receptors in patients with liver cirrhosis: possible association with hepatic function impairment. Cytokine. 2008;44:14-7 pubmed publisher..In conclusion, our study suggests that serum VEGF and VEGF-R1 may reflect the hepatic function impairment in liver cirrhosis and seems to be associated with portal hypertension symptoms. ..
- Duda D, Jain R. Premetastatic lung "niche": is vascular endothelial growth factor receptor 1 activation required?. Cancer Res. 2010;70:5670-3 pubmed publisher..pathways--activation and/or the recruitment of certain inflammatory cells--might depend on vascular endothelial growth factor receptor 1 (VEGFR1) activity...
- Dutta D, Ray S, Vivian J, Paul S. Activation of the VEGFR1 chromatin domain: an angiogenic signal-ETS1/HIF-2alpha regulatory axis. J Biol Chem. 2008;283:25404-13 pubmed publisher..These results establish an angiogenic signal-ETS1/HIF-2alpha axis that regulates the VEGFR1 chromatin domain to induce VEGFR1 transcription in endothelial cells and in differentiating embryonic stem cells. ..
- Shapiro N, Yano K, Okada H, Fischer C, Howell M, Spokes K, et al. A prospective, observational study of soluble FLT-1 and vascular endothelial growth factor in sepsis. Shock. 2008;29:452-7 pubmed
- Torry R, Tomanek R, Zheng W, Miller S, Labarrere C, Torry D. Hypoxia increases placenta growth factor expression in human myocardium and cultured neonatal rat cardiomyocytes. J Heart Lung Transplant. 2009;28:183-90 pubmed publisher..Collectively, these results provide important temporal and spatial evidence that endogenous PlGF may facilitate cardiac healing after myocardial hypoxia/ischemia. ..
- Banerjee S, Pancholi S, A Hern R, Ghazoui Z, Smith I, Dowsett M, et al. The effects of neoadjuvant anastrozole and tamoxifen on circulating vascular endothelial growth factor and soluble vascular endothelial growth factor receptor 1 in breast cancer. Clin Cancer Res. 2008;14:2656-63 pubmed publisher..This may be related to the relative effectiveness of the treatments. These data provide further support for cross talk between estrogen receptor and VEGF. ..
- Gu Y, Lewis D, Wang Y. Placental productions and expressions of soluble endoglin, soluble fms-like tyrosine kinase receptor-1, and placental growth factor in normal and preeclamptic pregnancies. J Clin Endocrinol Metab. 2008;93:260-6 pubmed..Lowered oxygen conditions promote sEng and sFlt-1, but reduce PlGF, productions by PE TCs. More glycosylated sEng and sFlt-1 are present in PE placentas. Trophoblasts release glycosylated sFlt-1, but unglycosylated sEng, in culture. ..
- Kaneko T, Zhang Z, Mantellini M, Karl E, Zeitlin B, Verhaegen M, et al. Bcl-2 orchestrates a cross-talk between endothelial and tumor cells that promotes tumor growth. Cancer Res. 2007;67:9685-93 pubmed..This work identifies a new function for Bcl-2 in cancer biology that is beyond its classic role in cell survival. ..
- Goncalves V, Gautier B, Regazzetti A, Coric P, Bouaziz S, Garbay C, et al. On-resin cyclization of peptide ligands of the Vascular Endothelial Growth Factor Receptor 1 by copper(I)-catalyzed 1,3-dipolar azide-alkyne cycloaddition. Bioorg Med Chem Lett. 2007;17:5590-4 pubmed..The reaction led exclusively to the formation of the expected cyclomonomeric products which acted as ligands of the Vascular Endothelial Growth Factor receptor 1.
- Hazarika S, Dokun A, Li Y, Popel A, Kontos C, Annex B. Impaired angiogenesis after hindlimb ischemia in type 2 diabetes mellitus: differential regulation of vascular endothelial growth factor receptor 1 and soluble vascular endothelial growth factor receptor 1. Circ Res. 2007;101:948-56 pubmed..After ischemia, maladaptive upregulation of these receptors further reduces the capacity of VEGF to induce an angiogenic response, which may provide a novel target for therapy. ..
- Kim S, Ryu H, Yang J, Kim M, Han J, Kim J, et al. Increased sFlt-1 to PlGF ratio in women who subsequently develop preeclampsia. J Korean Med Sci. 2007;22:873-7 pubmed..Accordingly, the sFlt-1/PlGF ratio may provide early prediction of subsequent development of preeclampsia. ..
- Kunizaki M, Hamamoto R, Silva F, Yamaguchi K, Nagayasu T, Shibuya M, et al. The lysine 831 of vascular endothelial growth factor receptor 1 is a novel target of methylation by SMYD3. Cancer Res. 2007;67:10759-65 pubmed..In the investigation of methyltransferase activity of SMYD3, we have found that vascular endothelial growth factor receptor 1 (VEGFR1) was also methylated by SMYD3...
- Muthig V, Gilsbach R, Haubold M, Philipp M, Ivacevic T, Gessler M, et al. Upregulation of soluble vascular endothelial growth factor receptor 1 contributes to angiogenesis defects in the placenta of alpha 2B-adrenoceptor deficient mice. Circ Res. 2007;101:682-91 pubmed
- Romero R, Nien J, Espinoza J, Todem D, Fu W, Chung H, et al. A longitudinal study of angiogenic (placental growth factor) and anti-angiogenic (soluble endoglin and soluble vascular endothelial growth factor receptor-1) factors in normal pregnancy and patients destined to develop preeclampsia and deliver a smal. J Matern Fetal Neonatal Med. 2008;21:9-23 pubmed publisher
- Woolcock J, Hennessy A, Xu B, Thornton C, Tooher J, Makris A, et al. Soluble Flt-1 as a diagnostic marker of pre-eclampsia. Aust N Z J Obstet Gynaecol. 2008;48:64-70 pubmed publisher..Serum levels of soluble fms-like tyrosine kinase (sFlt-1) increase in pre-eclampsia (PE)...
- Herr D, Rodewald M, Fraser H, Hack G, Konrad R, Kreienberg R, et al. Regulation of endothelial proliferation by the renin-angiotensin system in human umbilical vein endothelial cells. Reproduction. 2008;136:125-30 pubmed publisher..This is the first report of the RAS on the regulation of angiogenesis-associated genes in physiology. ..
- Tchaikovski V, Fellbrich G, Waltenberger J. The molecular basis of VEGFR-1 signal transduction pathways in primary human monocytes. Arterioscler Thromb Vasc Biol. 2008;28:322-8 pubmed..These pathways are critically involved in primary monocyte chemotaxis. ..
- Qazi U, Lam C, Karumanchi S, Petri M. Soluble Fms-like tyrosine kinase associated with preeclampsia in pregnancy in systemic lupus erythematosus. J Rheumatol. 2008;35:631-4 pubmed..This suggests that SLE pregnancies at risk for preeclampsia can be identified early in the pregnancy by sFlt-1, thus identifying them for high-risk obstetric referral and appropriate monitoring. ..
- Denizot Y, Leguyader A, Cornu E, Laskar M, Orsel I, Vincent C, et al. Release of soluble vascular endothelial growth factor receptor-1 (sFlt-1) during coronary artery bypass surgery. J Cardiothorac Surg. 2007;2:38 pubmed..sFlt-1 is released during CABG with ECC. It might be suggested that sFlt-1 production, by neutralizing VEGF and/or by inactivating membrane-bound Flt-1 and KDR receptors, might play a role in the occurrence of post-CABG complication. ..
- Du R, Lu K, Petritsch C, Liu P, Ganss R, Passegue E, et al. HIF1alpha induces the recruitment of bone marrow-derived vascular modulatory cells to regulate tumor angiogenesis and invasion. Cancer Cell. 2008;13:206-20 pubmed publisher..VEGF also directly regulates tumor cell invasiveness. When VEGF activity is impaired, tumor cells invade deep into the brain in the perivascular compartment. ..
- Alonci A, Allegra A, Bellomo G, Quartarone E, Oteri G, Nastro E, et al. Patients with bisphosphonate-associated osteonecrosis of the jaw have unmodified levels of soluble vascular endothelial growth factor receptor 1. Leuk Lymphoma. 2007;48:1852-4 pubmed
- Cerdeira A, Agrawal S, Staff A, Redman C, Vatish M. Angiogenic factors: Potential to change clinical practice in preeclampsia?. BJOG. 2017;: pubmed publisher..Here we review the most recent evidence regarding the potential of these factors as biomarkers and therapeutic targets for preeclampsia. This article is protected by copyright. All rights reserved...
- Chen J, Khalil R. Matrix Metalloproteinases in Normal Pregnancy and Preeclampsia. Prog Mol Biol Transl Sci. 2017;148:87-165 pubmed publisher..Understanding the role of MMPs in uteroplacental and vascular remodeling and function could help design new approaches for prediction and management of preeclampsia and premature labor. ..
- Takeda Y, Uemura S, Iwama H, Imagawa K, Nishida T, Onoue K, et al. Treatment with recombinant placental growth factor (PlGF) enhances both angiogenesis and arteriogenesis and improves survival after myocardial infarction. Circ J. 2009;73:1674-82 pubmed..Exogenous PlGF plays an important role in healing processes by improving cardiac function and stimulating angiogenesis following MI. It can be considered as a new therapeutic molecule. ..
- Kaliberova L, Kusmartsev S, Krendelchtchikova V, Stockard C, Grizzle W, Buchsbaum D, et al. Experimental cancer therapy using restoration of NAD+ -linked 15-hydroxyprostaglandin dehydrogenase expression. Mol Cancer Ther. 2009;8:3130-9 pubmed publisher..We have developed adenoviral vectors (Ad) encoding the 15-PGDH gene under control of the vascular endothelial growth factor receptor 1 (VEGFR1/flt-1; Adflt-PGDH) and the Cox-2 (Adcox-PGDH) promoters...
- Frampton G, Jones J, Rose M, Payne L. Placental growth factor (alone or in combination with soluble fms-like tyrosine kinase 1) as an aid to the assessment of women with suspected pre-eclampsia: systematic review and economic analysis. Health Technol Assess. 2016;20:1-160 pubmed..This study is registered as PROSPERO CRD42015017670. The National Institute for Health Research Health Technology Assessment programme. ..
- Shin E, Kang H, Yang H, Jung E, Jeung E. The Regulation of Fatty Acid Oxidation in Human Preeclampsia. Reprod Sci. 2016;23:1422-33 pubmed publisher..Consequently, these results suggest that expression of FAO-related genes is regulated by hypoxic conditions and onset time of PE and affects maternal gluconeogenesis during pregnancy in patients with PE. ..
- Chia S, Ellard S, Mates M, Welch S, Mihalcioiu C, Miller W, et al. A phase-I study of lapatinib in combination with foretinib, a c-MET, AXL and vascular endothelial growth factor receptor inhibitor, in human epidermal growth factor receptor 2 (HER-2)-positive metastatic breast cancer. Breast Cancer Res. 2017;19:54 pubmed publisher..The RP2D of the combined foretinib and lapatinib is 45 mg and 1000 mg PO OD, respectively. Limited activity was seen with this combination in a predominantly unselected cohort of HER-2-positive patients with MBC. ..
- Xie Y, Fan J, Chen J, Huang F, Cao B, Tam P, et al. A novel function for dendritic cell: clearance of VEGF via VEGF receptor-1. Biochem Biophys Res Commun. 2009;380:243-8 pubmed publisher..This study highlights a novel function of DCs and allows a better understanding of the DC-VEGF interaction. ..
- Librizzi M, Spencer J, Luparello C. Biological Effect of a Hybrid Anticancer Agent Based on Kinase and Histone Deacetylase Inhibitors on Triple-Negative (MDA-MB231) Breast Cancer Cells. Int J Mol Sci. 2016;17: pubmed publisher..the combination approach in finely tuning the biological activities of target cells and also showing the hybrid compound as an additional promising drug-like molecule for the prevention or therapy of "aggressive" breast carcinoma. ..
- Jacobsen R, Nowlan B, Brunck M, Barbier V, Winkler I, Levesque J. Fms-like tyrosine kinase 3 (Flt3) ligand depletes erythroid island macrophages and blocks medullar erythropoiesis in the mouse. Exp Hematol. 2016;44:207-12.e4 pubmed publisher..However, unlike G-CSF, Flt3-L had an indirect effect on EI macrophages, as it was not detected at the surface of EI macrophages or erythroid progenitors. ..
- Mimori K, Fukagawa T, Kosaka Y, Kita Y, Ishikawa K, Etoh T, et al. Hematogenous metastasis in gastric cancer requires isolated tumor cells and expression of vascular endothelial growth factor receptor-1. Clin Cancer Res. 2008;14:2609-16 pubmed publisher..This study indicates that the simultaneous presence of ITC and VEGFR-1 expression at premetastatic sites is clinically significant for disease progression. ..
- Budd S, Byfield G, Martiniuk D, Geisen P, Hartnett M. Reduction in endothelial tip cell filopodia corresponds to reduced intravitreous but not intraretinal vascularization in a model of ROP. Exp Eye Res. 2009;89:718-27 pubmed publisher..Reducing the number and length of filopodia/endothelial tip cell may reduce guidance cues for endothelial cells to migrate into the vitreous without interfering with migration into the retina toward a VEGF gradient. ..
- Kwinta P, Bik Multanowski M, Mitkowska Z, Tomasik T, Pietrzyk J. The clinical role of vascular endothelial growth factor (VEGF) system in the pathogenesis of retinopathy of prematurity. Graefes Arch Clin Exp Ophthalmol. 2008;246:1467-75 pubmed publisher..VEGF serum concentration assessment as early as on the 20th day of life appears to be a promising approach to recognize newborns at risk of the development of advanced ROP. ..
- Rades D, Setter C, Dunst J, Dahl O, Schild S, Noack F. Prognostic impact of VEGF and VEGF receptor 1 (FLT1) expression in patients irradiated for stage II/III non-small cell lung cancer (NSCLC). Strahlenther Onkol. 2010;186:307-14 pubmed publisher..85) had no significant impact. On multivariate analysis, lower N-category (p = 0.011) maintained significance. Tumor expression of VEGF and FLT1 appear to have no significant impact on LC, MFS, or OS in patients irradiated for NSCLC. ..
- Antoniou K, Soufla G, Proklou A, Margaritopoulos G, Choulaki C, Lymbouridou R, et al. Different activity of the biological axis VEGF-Flt-1 (fms-like tyrosine kinase 1) and CXC chemokines between pulmonary sarcoidosis and idiopathic pulmonary fibrosis: a bronchoalveolar lavage study. Clin Dev Immunol. 2009;2009:537929 pubmed publisher..However, further studies are needed in order to better investigate these enigmatic diseases. ..
- Rosu A, Ciurea P, Simionescu C, Margaritescu C, Musetescu A, Ciurea R, et al. The study of angiogenesis in early rheumatoid arthritis--clinical, immunohistochemical and immunological correlations. J Med Life. 2008;1:287-94 pubmed..The validation of preliminary conclusions oblige to continuous research through extending the study group and inclusion of several others biomarkers involved in synovial angiogenesis. ..
- Lieb W, Safa R, Benjamin E, Xanthakis V, Yin X, Sullivan L, et al. Vascular endothelial growth factor, its soluble receptor, and hepatocyte growth factor: clinical and genetic correlates and association with vascular function. Eur Heart J. 2009;30:1121-7 pubmed publisher..Increased angiogenesis and greater endothelial cell turnover may underlie associations of these growth factors with risk factors including smoking. ..
- Lee S, Hong Y, Pyun M, Felipe P, Choi S. Radiolabeling of monoclonal anti-vascular endothelial growth factor receptor 1 (VEGFR 1) with (177)Lu for potential use in radioimmunotherapy. Appl Radiat Isot. 2009;67:1185-9 pubmed publisherThe main goal of this study was to optimize the radioimmunoconjugation of monoclonal anti-vascular endothelial growth factor receptor 1 (VEGFR 1) with (177)Lu as a potential angiogenic molecular tracer for radioimmunotherapy (RIT)...
- Meier K, Lehr C, Daum N. Differentiation potential of human pancreatic stem cells for epithelial- and endothelial-like cell types. Ann Anat. 2009;191:70-82 pubmed publisher..These results confirm that PSC possess endothelial and epithelial properties. Furthermore, epithelial characteristics represented by expression of CDH 1 were altered by coculture with epithelial cell lines. ..
- Kumar R, Harris Hooker S, Sanford G. The expression of growth factors and their receptors in retinal and endothelial cells cocultured in the rotating bioreactor. Ethn Dis. 2008;18:S2-44-50 pubmed..These findings suggest that retinal/endothelial cell coculture in the horizontally rotating bioreactor may be a very good model for investigating the role of growth factors in the neovascularization seen in human ocular disorders. ..
- Orlandi A, Di Lascio A, Francesconi A, Scioli M, Arcuri G, Ferlosio A, et al. Stem cell marker expression and proliferation and apoptosis of vascular smooth muscle cells. Cell Cycle. 2008;7:3889-97 pubmed