TY - JOUR
T1 - A systems biology perspective on sVEGFR1
T2 - Its biological function, pathogenic role and therapeutic use
AU - Wu, Florence T.H.
AU - Stefanini, Marianne O.
AU - Gabhann, Feilim Mac
AU - Kontos, Christopher D.
AU - Annex, Brian H.
AU - Popel, Aleksander S.
PY - 2010/3
Y1 - 2010/3
N2 - Angiogenesis is the growth of new capillaries from pre-existent microvasculature. A wide range of pathological conditions, from atherosclerosis to cancer, can be attributed to either excessive or deficient angiogenesis. Central to the physiological regulation of angiogenesis is the vascular endothelial growth factor (VEGF) system - its ligands and receptors (VEGFRs) are thus prime molecular targets of pro-angiogenic and anti-angiogenic therapies. Of growing interest as a prognostic marker and therapeutic target in angiogenesis-dependent diseases is soluble VEGF receptor-1 (sVEGFR1, also known as sFlt-1) - a truncated version of the cell membrane-spanning VEGFR1. For instance, it is known that sVEGFR1 is involved in the endothelial dysfunction characterizing the pregnancy disorder of pre-eclampsia, and sVEGFR1's therapeutic potential as an anti-angiogenic agent is being evaluated in pre-clinical models of cancer. This mini review begins with an examination of the protein domain structure and biomolecular interactions of sVEGFR1 in relation to the full-length VEGFR1. A synopsis of known and inferred physiological and pathological roles of sVEGFR1 is then given, with emphasis on the utility of computational systems biology models in deciphering the molecular mechanisms by which sVEGFR1's purported biological functions occur. Finally, we present the need for a systems biology perspective in interpreting circulating VEGF and sVEGFR1 concentrations as surrogate markers of angiogenic status in angiogenesis-dependent diseases.
AB - Angiogenesis is the growth of new capillaries from pre-existent microvasculature. A wide range of pathological conditions, from atherosclerosis to cancer, can be attributed to either excessive or deficient angiogenesis. Central to the physiological regulation of angiogenesis is the vascular endothelial growth factor (VEGF) system - its ligands and receptors (VEGFRs) are thus prime molecular targets of pro-angiogenic and anti-angiogenic therapies. Of growing interest as a prognostic marker and therapeutic target in angiogenesis-dependent diseases is soluble VEGF receptor-1 (sVEGFR1, also known as sFlt-1) - a truncated version of the cell membrane-spanning VEGFR1. For instance, it is known that sVEGFR1 is involved in the endothelial dysfunction characterizing the pregnancy disorder of pre-eclampsia, and sVEGFR1's therapeutic potential as an anti-angiogenic agent is being evaluated in pre-clinical models of cancer. This mini review begins with an examination of the protein domain structure and biomolecular interactions of sVEGFR1 in relation to the full-length VEGFR1. A synopsis of known and inferred physiological and pathological roles of sVEGFR1 is then given, with emphasis on the utility of computational systems biology models in deciphering the molecular mechanisms by which sVEGFR1's purported biological functions occur. Finally, we present the need for a systems biology perspective in interpreting circulating VEGF and sVEGFR1 concentrations as surrogate markers of angiogenic status in angiogenesis-dependent diseases.
KW - Angiogenesis
KW - Computational modelling
KW - Molecular systems biology
KW - Multi-scale modelling
KW - Neovascularization
KW - Soluble fms-like tyrosine kinase 1 (sFlt-1)
KW - Systems pharmacology
KW - Vascular endothelial growth factor (VEGF)
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UR - http://www.scopus.com/inward/citedby.url?scp=77952593669&partnerID=8YFLogxK
U2 - 10.1111/j.1582-4934.2009.00941.x
DO - 10.1111/j.1582-4934.2009.00941.x
M3 - Article
C2 - 19840194
AN - SCOPUS:77952593669
SN - 1582-1838
VL - 14
SP - 528
EP - 552
JO - Journal of Cellular and Molecular Medicine
JF - Journal of Cellular and Molecular Medicine
IS - 3
ER -