Research Topics
Genomes and Genes | Steven J HarperSummaryAffiliation: University of Bristol Country: UK Publications
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Publications
Expression of neuropilin-1 by human glomerular epithelial cells in vitro and in vivoS J Harper
Academic Renal Unit, University of Bristol, Southmead Hospital, Westbury on Trym, Bristol B10 5NB, U K
Clin Sci (Lond) 101:439-46. 2001..Functional studies will be required to address the potential significance of this finding in terms of an autocrine loop or VEGF sequestration...
Elevated plasma vascular endothelial growth factor levels in non-diabetic predialysis uraemiaSteven J Harper
Academic Renal Laboratories, University of Bristol, Westbury on Trym, Bristol, UK
Nephron 90:341-3. 2002..002. In conclusion, free plasma VEGF levels are high in chronic renal impairment. We hypothesise that this potent growth and permeability factor may contribute to the endothelial dysfunction of uraemia...
VEGF-A splicing: the key to anti-angiogenic therapeutics?Steven J Harper
Microvascular Research Laboratories, Department of Physiology and Pharmacology, Bristol Heart Institute, School of Veterinary Science, University of Bristol, Southwell Street, Bristol BS2 8EJ, UK
Nat Rev Cancer 8:880-7. 2008....
Expression of pro- and anti-angiogenic isoforms of VEGF is differentially regulated by splicing and growth factorsDawid G Nowak
Microvascular Research Laboratories, Bristol Heart Institute, Department of Physiology and Pharmacology, School of Veterinary Sciences, University of Bristol, Southwell Street, Bristol BS2 8EJ, UK
J Cell Sci 121:3487-95. 2008....
Regulation of vascular endothelial growth factor (VEGF) splicing from pro-angiogenic to anti-angiogenic isoforms: a novel therapeutic strategy for angiogenesisDawid G Nowak
Microvascular Research Laboratories, Bristol Heart Institute, Department of Physiology and Pharmacology, School of Veterinary Sciences, University of Bristol, Bristol BS2 8EJ, United Kingdom
J Biol Chem 285:5532-40. 2010..Injection of an SRPK1/2 inhibitor reduced angiogenesis in a mouse model of retinal neovascularization, suggesting that regulation of alternative splicing could be a potential therapeutic strategy in angiogenic pathologies...
VEGF-A165b is cytoprotective and antiangiogenic in the retinaAnette L Magnussen
Microvascular Research Laboratories, Bristol Heart Institute, Department of Physiology and Pharmacology, School of Veterinary Sciences, University of Bristol, Bristol, UK
Invest Ophthalmol Vis Sci 51:4273-81. 2010..Here the authors investigate the antiangiogenic activity of VEGF(165)b and its effect on retinal epithelial and endothelial cell survival...
Recombinant human VEGF165b inhibits experimental choroidal neovascularizationJing Hua
Microvascular Research Laboratories, Department of Physiology and Pharmacology, Bristol Heart Institute, School of Veterinary Sciences, University of Bristol, Bristol, UK
Invest Ophthalmol Vis Sci 51:4282-8. 2010..It is the proangiogenic family that is responsible for the blood vessel growth seen in AMD...
Balance of pro- versus anti-angiogenic splice isoforms of vascular endothelial growth factor as a regulator of neuroblastoma growthMaria Peiris-Pagès
Cellular and Molecular Medicine, University of Bristol, School of Medical Sciences, University Walk, Bristol BS8 1TD, UK
J Pathol 222:138-47. 2010..In conclusion, VEGF(165)b is an effective inhibitor of NB growth. These findings provide the rationale for further investigation of VEGF(165)b in NB and other paediatric malignancies...
WT1 mutants reveal SRPK1 to be a downstream angiogenesis target by altering VEGF splicingElianna M Amin
Centre for Research in Biomedicine, University of the West of England, Bristol, UK
Cancer Cell 20:768-80. 2011..Altered VEGF splicing was reversed by wild-type WT1, knockdown of SRSF1, or SRPK1 and inhibition of SRPK1, which prevented in vitro and in vivo angiogenesis and associated tumor growth...
VEGF-C induced angiogenesis preferentially occurs at a distance from lymphangiogenesisAndrew V Benest
Microvascular Research Laboratories, Department of Physiology, University of Bristol, BS2 8EJ Bristol, UK
Cardiovasc Res 78:315-23. 2008....
Differentiated human podocytes endogenously express an inhibitory isoform of vascular endothelial growth factor (VEGF165b) mRNA and proteinTai Gen Cui
Microvascula Research Laboratories, Dept of Physiology, Preclinical Veterinary School, Univ of Bristol, Southwell St, Bristol BS2 8EJ, UK
Am J Physiol Renal Physiol 286:F767-73. 2004....
The endogenous anti-angiogenic family of splice variants of VEGF, VEGFxxxb, are down-regulated in pre-eclamptic placentae at termDavid O Bates
Microvascular Research Laboratories, Department of Physiology, Preclinical Veterinary School, University of Bristol, Bristol BS2 8EJ, UK
Clin Sci (Lond) 110:575-85. 2006....
The anti-angiogenic isoforms of VEGF in health and diseaseYan Qiu
Department of Physiology and Pharmacology, Microvascular Research Laboratories, Bristol Heart Institute, School of Veterinary Sciences, University of Bristol, Southwell Street, Bristol BS2 8EJ, UK
Biochem Soc Trans 37:1207-13. 2009....
Angiopoietin-1 alters microvascular permeability coefficients in vivo via modification of endothelial glycocalyxAndrew H J Salmon
Department of Physiology and Pharmacology, Preclinical Veterinary School, Microvascular Research Laboratories, Bristol Heart Institute, University of Bristol, Southwell Street, Bristol, UK
Cardiovasc Res 83:24-33. 2009..In this study, we wished to determine whether angiopoietin-1 (Ang1) modified the permeability coefficients of non-inflamed, intact continuous, and fenestrated microvessels in vivo and to elucidate the underlying cellular mechanisms...
Nephrotic plasma alters slit diaphragm-dependent signaling and translocates nephrin, Podocin, and CD2 associated protein in cultured human podocytesRichard J M Coward
Academic and Children s Renal Unit, Southmead Hospital, University of Bristol, Bristol, UK
J Am Soc Nephrol 16:629-37. 2005..This work demonstrates that nephrotic plasma seems to be deficient in factors that act via the podocyte SD complex, which are essential in maintaining its physiologic function...
Functional evidence that vascular endothelial growth factor may act as an autocrine factor on human podocytesRebecca R Foster
Microvascular Research Laboratories, Department of Physiology, University of Bristol, Preclinical Veterinary School, United Kingdom
Am J Physiol Renal Physiol 284:F1263-73. 2003..These results indicate that one of the functions of VEGF secreted from podocytes may be to act as an autocrine factor on calcium homeostasis and cell survival...
Vascular endothelial growth factor and nephrin interact and reduce apoptosis in human podocytesRebecca R Foster
Microvascular Research Laboratories, Department of Physiology, University of Bristol, Preclinical Veterinary School, Southwell St, Bristol BS2 8EJ, UK
Am J Physiol Renal Physiol 288:F48-57. 2005..However, the involvement of AKT in this survival response in normal human podocytes is not clear...
VEGF165b, an inhibitory splice variant of vascular endothelial growth factor, is down-regulated in renal cell carcinomaDavid O Bates
Microvascular Research Laboratories, Department of Physiology, Preclinical Veterinary School, University of Bristol, Bristol BS2 8EJ, United Kingdom
Cancer Res 62:4123-31. 2002..This novel isoform VEGF165b is therefore an endogenous inhibitory form of VEGF that is down-regulated in renal tumors and, therefore, may be anti-angiogenesis...
VEGF165b overexpression restores normal glomerular water permeability in VEGF164-overexpressing adult miceSebastian Oltean
Microvascular Research Laboratories, School of Physiology and Pharmacology, Univ of Bristol, Preclinical Veterinary School, Southwell St, Bristol, United Kingdom BS2 8EJ
Am J Physiol Renal Physiol 303:F1026-36. 2012..VEGF(165)b is capable of preventing VEGF(164)-induced changes in glomerular permeability and ultrastructure in vivo...
Loss of the endothelial glycocalyx links albuminuria and vascular dysfunctionAndrew H J Salmon
Microvascular Research Laboratories, School of Physiology and Pharmacology, University of Bristol, Southwell Street, Bristol, UK
J Am Soc Nephrol 23:1339-50. 2012..Taken together, these results suggest that widespread loss of the endothelial surface layer links albuminuric kidney disease with systemic vascular dysfunction, providing a potential therapeutic target for proteinuric kidney disease...
Therapeutic potential of manipulating VEGF splice isoforms in oncologyEmma S Rennel
Microvascular Research Laboratories, Department of Physiology and Pharmacology, School of Veterinary Sciences, University of Bristol, Bristol, UK
Future Oncol 5:703-12. 2009..The concept here is to target the splicing mechanisms that control splice site choice in the VEGF-A mRNA. Recent evidence on the pharmacological possibilities of such splice factors is described...
Vascular endothelial growth factor increases the ultrafiltration coefficient in isolated intact Wistar rat glomeruliAndrew H J Salmon
Microvascular Research Laboratories, Department of Physiology, School of Veterinary Sciences, University of Bristol, Southwell Street, Bristol BS2 8EJ, UK
J Physiol 570:141-56. 2006..We suggest that glomerular VEGF contributes to the high physiological permeability of mammalian glomeruli to water through an action on endothelial cells...
Molecular diversity of VEGF-A as a regulator of its biological activityJeanette Woolard
Department of Physiology and Pharmacology, Bristol Heart Institute, School of Veterinary Sciences, University of Bristol, Bristol, UK
Microcirculation 16:572-92. 2009..Here, we examine the molecular diversity of VEGF-A as a regulator of its biological activity and compare the role of the pro- and antiangiogenic VEGF-A splice isoforms in both normal and pathophysiological processes...
VEGF in the lung: a role for novel isoformsJulia Varet
Lung Research Group, Department of Clinical Science at North Bristol, University of Bristol Paul O Gorman Lifeline Centre, Southmead Hospital, Westbury on Trym, United Kingdom
Am J Physiol Lung Cell Mol Physiol 298:L768-74. 2010..A specific functional effect on primary human endothelial and alveolar epithelial cells has also been shown. These data suggest that the VEGF(xxx)b family may have a role in repair after lung injury...
Arteriolar genesis and angiogenesis induced by endothelial nitric oxide synthase overexpression results in a mature vasculatureAndrew V Benest
Microvascular Research Laboratories, Bristol Heart Institute, Department of Physiology, University of Bristol, Southwell Street, Bristol BS2 8EJ, United Kingdom
Arterioscler Thromb Vasc Biol 28:1462-8. 2008..Generation of physiologically active vascular beds by delivery of combinations of growth factors offers promise for vascular gene therapy...
The alternatively spliced anti-angiogenic family of VEGF isoforms VEGFxxxb in human kidney developmentHeather S Bevan
Microvascular Research Laboratories, Department of Physiology, University of Bristol, Bristol, UK
Nephron Physiol 110:p57-67. 2008..VEGF(165)b, the first described exon 8b-containing isoform, antagonises VEGF(165) and is anti-angiogenic in vivo...
Hyperglycemia stimulates a sustained increase in hydraulic conductivity in vivo without any change in reflection coefficientRachel M Perrin
Microvascular Research Laboratories, Department of Physiology, University of Bristol, Preclinical Veterinary School, Bristol, UK
Microcirculation 14:683-96. 2007..The mechanisms underlying increased permeability, however, are poorly understood...
Failure to up-regulate VEGF165b in maternal plasma is a first trimester predictive marker for pre-eclampsiaVictoria L Bills
Microvascular Research Laboratories, Department of Physiology, Preclinical Veterinary School, University of Bristol, Bristol BS2 8EJ, U K
Clin Sci (Lond) 116:265-72. 2009..In conclusion, low VEGF(165)b may therefore be a clinically useful first trimester plasma marker for increased risk of pre-eclampsia...
Mammary alveolar development during lactation is inhibited by the endogenous antiangiogenic growth factor isoform, VEGF165bYan Qiu
Microvascular Research Laboratories, School of Veterinary Sciences, University of Bristol, Bristol, UK
FASEB J 22:1104-12. 2008..This study provides the first evidence for the role of endogenous antiangiogenic VEGF isoforms in normal physiology--their down-regulation is required for effective milk production...
Therapeutic potential of inhibitory VEGF splice variantsDavid O Bates
University of Bristol, Microvascular Research Laboratories, Department of Physiology, Preclinical Veterinary School, Southwell Street, Bristol, BS2 8EJ, UK
Future Oncol 1:467-73. 2005..The discovery, mechanism of action, preclinical evaluation, and the potential uses of these isoforms in future cancer therapy will be discussed herein...
Glomerular filtration into the subpodocyte space is highly restricted under physiological perfusion conditionsChristopher R Neal
Dept of Physiology, Univ of Bristol, Southwell St, Bristol BS2 8EJ, UK
Am J Physiol Renal Physiol 293:F1787-98. 2007..This suggests a physiological role of the podocyte in the regulation of glomerular fluid flux across most of the GFB...
Recombinant human VEGF165b protein is an effective anti-cancer agent in miceEmma S Rennel
Microvascular Research Laboratories, Department of Physiology and Pharmacology, School of Veterinary Science, University of Bristol, Southwell Street, Bristol BS2 8EJ, United Kingdom
Eur J Cancer 44:1883-94. 2008....
VEGF165b, an inhibitory vascular endothelial growth factor splice variant: mechanism of action, in vivo effect on angiogenesis and endogenous protein expressionJeanette Woolard
Microvascular Research Laboratories, Department of Physiology, Preclinical Veterinary School, University of Bristol, Southwell Street, Bristol, United Kingdom
Cancer Res 64:7822-35. 2004..These results suggest that regulation of VEGF splicing may be a critical switch from an antiangiogenic to a proangiogenic phenotype...
Three-dimensional reconstruction of glomeruli by electron microscopy reveals a distinct restrictive urinary subpodocyte spaceChristopher R Neal
Microvascular Research Laboratories, Department of Physiology, Preclinical Veterinary School, University of Bristol, Southwell Street, Bristol BS2 8EJ, UK
J Am Soc Nephrol 16:1223-35. 2005..The physiologic role of the restrictive SPS is yet to be determined but likely possibilities include regulation of glomerular filtration and cleaning of the glomerular filtration barrier...
New aspects of glomerular filtration barrier structure and function: five layers (at least) not threeAndrew H J Salmon
Microvascular Research Laboratories, Bristol Heart Institute, Department of Physiology and Pharmacology, School of Veterinary Sciences, Southwell Street, University of Bristol, Bristol, UK
Curr Opin Nephrol Hypertens 18:197-205. 2009..We review recent work demonstrating the functional importance of two additional layers: the endothelial surface layer (ESL) and the subpodocyte space (SPS)...
VEGF and angiopoietin-1 stimulate different angiogenic phenotypes that combine to enhance functional neovascularization in adult tissueAndrew V Benest
Microvascular Research Laboratories, Department of Physiology, University of Bristol, Bristol, UK
Microcirculation 13:423-37. 2006..These results suggest that effective revascularization therapy may require combination growth factor treatment...
A human neutralizing antibody specific to Ang-2 inhibits ocular angiogenesisEmma S Rennel
Microvascular Research Laboratories, Bristol Heart Institute, School of Physiology and Pharmacology, Veterinary Sciences Building, University of Bristol, Bristol, UK
Microcirculation 18:598-607. 2011..Our objective was to determine the requirement of ocular angiogenesis for Ang2 in animal models of disease...
An adenovirus-mediated gene-transfer model of angiogenesis in rat mesenteryWen-Ying Wang
Microvascular Research Laboratories, Department of Physiology, Preclinical Veterinary School, University of Bristol, Bristol, UK
Microcirculation 11:361-75. 2004..This two-dimensional model of VEGF-induced angiogenesis is amenable to physiological, biochemical, and molecular assessment and may be a useful tool to help understand mechanisms of angiogenesis...
Plasma from women with severe pre-eclampsia increases microvascular permeability in an animal model in vivoChristopher R Neal
Microvascular Research Laboratories, Department of Physiology, Preclinical Veterinary School, University of Bristol, Bristol, BS2 8EJ, UK
Clin Sci (Lond) 107:399-405. 2004..The nature of the circulating macromolecule is not known, except that it is, or is bound to, a molecule greater than 12 kDa...
Association between VEGF splice isoforms and progression-free survival in metastatic colorectal cancer patients treated with bevacizumabDavid O Bates
Microvascular Research Laboratories, Department of Physiology and Pharmacology, University of Bristol, Bristol, United Kingdom
Clin Cancer Res 18:6384-91. 2012..We tested the hypothesis that prolonged progression-free survival (PFS) would occur only in patients with low relative VEGF(165)b levels treated with bevacizumab...
Human uremic plasma increases microvascular permeability to water and proteins in vivoSteven J Harper
Academic Renal Laboratories, University of Bristol, Southmead Hospital, Bristol, England, United Kingdom
Kidney Int 61:1416-22. 2002..53). CONCLUSIONS: These results suggest that one or more circulating macromolecules in uremic plasma are able to increase transvascular solute and fluid flux, and may underlie the increased cardiovascular risk found in these patients...
Alternative splicing in angiogenesis: the vascular endothelial growth factor paradigmMichael R Ladomery
Centre for Research in Biomedicine, Bristol Genomics Research Institute, Faculty of Applied Sciences, University of the West of England, Coldharbour Lane, Bristol BS16 1QY, UK
Cancer Lett 249:133-42. 2007..Understanding what regulates VEGF(xxx)b alternative splicing, and therefore the balance of pro- and antiangiogenic isoforms is of great importance and will be explored in detail over the next few years...
Evidence for restriction of fluid and solute movement across the glomerular capillary wall by the subpodocyte spaceAndrew H J Salmon
ZNI 335, Zilkha Neurogenetic Institute, 1501 San Pablo St, Keck School of Medicine, Univ of Southern California, Los Angeles, CA 90089, USA
Am J Physiol Renal Physiol 293:F1777-86. 2007..These observations indicate both ultrafiltration and hydraulic resistance imparted by the SPS, demonstrating the potential physiological contribution of the SPS to glomerular permeability...
Vascular endothelial growth factor (VEGF)-A165b is a weak in vitro agonist for VEGF receptor-2 due to lack of coreceptor binding and deficient regulation of kinase activityHarukiyo Kawamura
Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden
Cancer Res 68:4683-92. 2008..Our data indicate that loss of VEGFR-2/NRP1 complex formation and Y1052 phosphorylation contribute to the lack of angiogenic properties of VEGF-A165b...
