Skip to main content
Top
Published in: Metabolic Brain Disease 2/2017

01-04-2017 | Original Article

Changes in serum vascular endothelial growth factor and endostatin concentrations associated with circulating endothelial progenitor cells after acute ischemic stroke

Authors: Lixia Xue, Hao Chen, Ting Zhang, Jingjiong Chen, Zhi Geng, Yuwu Zhao

Published in: Metabolic Brain Disease | Issue 2/2017

Login to get access

Abstract

Angiogenesis is an important pathophysiological response to cerebral ischemia, and can be modulated by vascular endothelial growth factor (VEGF) and endostatin. Circulating endothelial progenitor cells (EPCs) also play an important role as an endogenous repair mechanism for ischemic injury. We sought to investigate early changes in the expression of VEGF and endostatin in serum and the circulating EPCs in patients with acute ischemic stroke (AIS) and analyzed the relations between them. The peripheral blood and serum samples were obtained from 30 patients at 1, 3, 5 and 7 d after AIS. Flow cytometry was used to quantify EPCs, and VEGF and endostatin were measured by enzyme linked immunosorbent assay. Correlation analysis was performed to assess the relations between them. Receiver operating characteristic (ROC) curve was used to appraise the value of EPCs levels in predicting the 90-day prognosis after AIS. Compared with control subjects, circulating EPCs numbers increased from a very lower initial level (P < 0.001) until 7 d after AIS. Serum VEGF and endostatin levels increased and peaked at 3 d and 5 d post-stroke (both P < 0.001), respectively. A significant correlation (P = 0.001) was found between peak serum VEGF concentration and peak endostatin concentration. VEGF/endostatin ratio at day 1 and day 3 after AIS significantly correlated with circulating EPCs numbers at day 5 (P < 0.001) and day 7 post-stroke (P < 0.001). ROC curve analysis suggested that circulating EPCs number at day 7 had a significantly predictive power for good prognosis. VEGF and endostatin may mediate EPCs proliferation in the early phase of ischemic stroke, and the circulating EPCs levels can be a predictor of clinical outcome in AIS.
Literature
go back to reference Chen H, Xue LX, Cao HL, Chen SW, Guo Y, Gao WW, Ju SM, Tian HL (2013) Endostatin/collagen XVIII is increased in cerebrospinal fluid after severe traumatic brain injury. Biomed Res Int 2013:402375PubMedPubMedCentral Chen H, Xue LX, Cao HL, Chen SW, Guo Y, Gao WW, Ju SM, Tian HL (2013) Endostatin/collagen XVIII is increased in cerebrospinal fluid after severe traumatic brain injury. Biomed Res Int 2013:402375PubMedPubMedCentral
go back to reference Chu K, Jung K-H, Lee S-T, Park HK, Sinn DI, Kim JM, Kim SJ, Song EC, Kim M, Lee SK, Roh JK (2008) Circulating endothelial progenitor cells as a new marker of endothelial dysfunction or repair in acute stroke. Stroke 39:1441–1447CrossRefPubMed Chu K, Jung K-H, Lee S-T, Park HK, Sinn DI, Kim JM, Kim SJ, Song EC, Kim M, Lee SK, Roh JK (2008) Circulating endothelial progenitor cells as a new marker of endothelial dysfunction or repair in acute stroke. Stroke 39:1441–1447CrossRefPubMed
go back to reference Chung CP, Huang PH, Chen JS, Chen JW, Yang KY (2015) The level of circulating endothelial progenitor cell is associated with cerebral vasoreactivity: a pilot study. Biomed Res Int 2015:258279PubMedPubMedCentral Chung CP, Huang PH, Chen JS, Chen JW, Yang KY (2015) The level of circulating endothelial progenitor cell is associated with cerebral vasoreactivity: a pilot study. Biomed Res Int 2015:258279PubMedPubMedCentral
go back to reference Horie N, Pereira MP, Niizuma K, Sun G, Keren-Gill H, Encarnacion A, Shamloo M, Hamilton SA, Jiang K, Huhn S, Palmer TD, Bliss TM, Steinberg GK (2011) Transplanted stem cell-secreted vascular endothelial growth factor effects poststroke recovery, inflammation, and vascular repair. Stem Cells 29:274–285CrossRefPubMed Horie N, Pereira MP, Niizuma K, Sun G, Keren-Gill H, Encarnacion A, Shamloo M, Hamilton SA, Jiang K, Huhn S, Palmer TD, Bliss TM, Steinberg GK (2011) Transplanted stem cell-secreted vascular endothelial growth factor effects poststroke recovery, inflammation, and vascular repair. Stem Cells 29:274–285CrossRefPubMed
go back to reference Hou Q, Ling L, Wang F, Xing S, Pei Z, Zeng J (2010) Endostatin expression in neurons during the early stage of cerebral ischemia is associated with neuronal apoptotic cell death in adult hypertensive rat model of stroke. Brain Res 1311:182–188CrossRefPubMed Hou Q, Ling L, Wang F, Xing S, Pei Z, Zeng J (2010) Endostatin expression in neurons during the early stage of cerebral ischemia is associated with neuronal apoptotic cell death in adult hypertensive rat model of stroke. Brain Res 1311:182–188CrossRefPubMed
go back to reference Ma J, Luo Y (2008) Effects of electroacupuncture on expressions of angiogenesis factors and anti-angiogenesis factors in brain of experimental cerebral ischemic rats after reperfusion. J Tradit Chin Med 28:217–222CrossRefPubMed Ma J, Luo Y (2008) Effects of electroacupuncture on expressions of angiogenesis factors and anti-angiogenesis factors in brain of experimental cerebral ischemic rats after reperfusion. J Tradit Chin Med 28:217–222CrossRefPubMed
go back to reference Ma Y, Zechariah A, Qu Y, Hermann DM (2012) Effects of vascular endothelial growth factor in ischemic stroke. J Neurosci Res 90:1873–1882CrossRefPubMed Ma Y, Zechariah A, Qu Y, Hermann DM (2012) Effects of vascular endothelial growth factor in ischemic stroke. J Neurosci Res 90:1873–1882CrossRefPubMed
go back to reference Ma F, Morancho A, Montaner J, Rosell A (2015) Endothelial progenitor cells and revascularization following stroke. Brain Res 1623:150–159CrossRefPubMed Ma F, Morancho A, Montaner J, Rosell A (2015) Endothelial progenitor cells and revascularization following stroke. Brain Res 1623:150–159CrossRefPubMed
go back to reference Marti HJ, Bernaudin M, Bellail A, Schoch H, Euler M, Petit E, Risau W (2000) Hypoxia-induced vascular endothelial growth factor expression precedes neovascularization after cerebral ischemia. Am J Pathol 156:965–976CrossRefPubMedPubMedCentral Marti HJ, Bernaudin M, Bellail A, Schoch H, Euler M, Petit E, Risau W (2000) Hypoxia-induced vascular endothelial growth factor expression precedes neovascularization after cerebral ischemia. Am J Pathol 156:965–976CrossRefPubMedPubMedCentral
go back to reference Martí-Fàbregas J, Crespo J, Delgado-Mederos R, Martínez-Ramírez S, Peña E, Marín R, Dinia L, Jiménez-Xarrié E, Fernández-Arcos A, Pérez-Pérez J, Querol L, Suárez-Calvet M, Badimon L (2013) Endothelial progenitor cells in acute ischemic stroke. Brain Behav 3:649–655CrossRefPubMedPubMedCentral Martí-Fàbregas J, Crespo J, Delgado-Mederos R, Martínez-Ramírez S, Peña E, Marín R, Dinia L, Jiménez-Xarrié E, Fernández-Arcos A, Pérez-Pérez J, Querol L, Suárez-Calvet M, Badimon L (2013) Endothelial progenitor cells in acute ischemic stroke. Brain Behav 3:649–655CrossRefPubMedPubMedCentral
go back to reference Martí-Fàbregas J, Delgado-Mederos R, Crespo J, Peña E, Marín R, Jiménez-Xarrié E, Fernández-Arcos A, Pérez-Pérez J, Martínez-Domeño A, Camps-Renom P, Prats-Sánchez L, Casoni F, Badimon L (2015) Circulating endothelial progenitor cells and the risk of vascular events after ischemic stroke. PLoS One 10:e0124895CrossRefPubMedPubMedCentral Martí-Fàbregas J, Delgado-Mederos R, Crespo J, Peña E, Marín R, Jiménez-Xarrié E, Fernández-Arcos A, Pérez-Pérez J, Martínez-Domeño A, Camps-Renom P, Prats-Sánchez L, Casoni F, Badimon L (2015) Circulating endothelial progenitor cells and the risk of vascular events after ischemic stroke. PLoS One 10:e0124895CrossRefPubMedPubMedCentral
go back to reference Mund JA, Case J (2011) The ontogeny of endothelial progenitor cells through flow cytometry. Curr Opin Hematol 18:166–170CrossRefPubMed Mund JA, Case J (2011) The ontogeny of endothelial progenitor cells through flow cytometry. Curr Opin Hematol 18:166–170CrossRefPubMed
go back to reference Navarro-Sobrino M, Rosell A, Hernández-Guillamon M, Penalba A, Boada C, Domingues-Montanari S, Ribó M, Alvarez-Sabín J, Montaner J (2011) A large screening of angiogenesis biomarkers and their association with neurological outcome after ischemic stroke. Atherosclerosis 216:205–211CrossRefPubMed Navarro-Sobrino M, Rosell A, Hernández-Guillamon M, Penalba A, Boada C, Domingues-Montanari S, Ribó M, Alvarez-Sabín J, Montaner J (2011) A large screening of angiogenesis biomarkers and their association with neurological outcome after ischemic stroke. Atherosclerosis 216:205–211CrossRefPubMed
go back to reference Pikula A, Beiser AS, Chen TC, Preis SR, Vorgias D, DeCarli C, Au R, Kelly-Hayes M, Kase CS, Wolf PA, Vasan RS, Seshadri S (2013) Serum brain-derived neurotrophic factor and vascular endothelial growth factor levels are associated with risk of stroke and vascular brain injury: Framingham study. Stroke 44:2768–2775CrossRefPubMed Pikula A, Beiser AS, Chen TC, Preis SR, Vorgias D, DeCarli C, Au R, Kelly-Hayes M, Kase CS, Wolf PA, Vasan RS, Seshadri S (2013) Serum brain-derived neurotrophic factor and vascular endothelial growth factor levels are associated with risk of stroke and vascular brain injury: Framingham study. Stroke 44:2768–2775CrossRefPubMed
go back to reference Sobrino T, Hurtado O, Moro MA, Rodriguez-Yanez M, Castellanos M, Brea D, Moldes O, Blanco M, Arenillas JF, Leira R, Davalos A, Lizasoain I, Castillo J (2007) The increase of circulating endothelial progenitor cells after acute ischemic stroke is associated with good outcome. Stroke 38:2759–2764CrossRefPubMed Sobrino T, Hurtado O, Moro MA, Rodriguez-Yanez M, Castellanos M, Brea D, Moldes O, Blanco M, Arenillas JF, Leira R, Davalos A, Lizasoain I, Castillo J (2007) The increase of circulating endothelial progenitor cells after acute ischemic stroke is associated with good outcome. Stroke 38:2759–2764CrossRefPubMed
go back to reference Sobrino T, Pérez-Mato M, Brea D, Rodríguez-Yáñez M, Blanco M, Castillo J (2012) Temporal profile of molecular signatures associated with circulating endothelial progenitor cells in human ischemic stroke. J Neurosci Res 90:1788–1793CrossRefPubMed Sobrino T, Pérez-Mato M, Brea D, Rodríguez-Yáñez M, Blanco M, Castillo J (2012) Temporal profile of molecular signatures associated with circulating endothelial progenitor cells in human ischemic stroke. J Neurosci Res 90:1788–1793CrossRefPubMed
go back to reference Stowe AM, Plautz EJ, Eisner-Janowicz I, Frost SB, Barbay S, Zoubina EV, Dancause N, Taylor MD, Nudo RJ (2007) VEGF protein associates to neurons in remote regions following cortical infarct. J Cereb Blood Flow Metab 27:76–85CrossRefPubMed Stowe AM, Plautz EJ, Eisner-Janowicz I, Frost SB, Barbay S, Zoubina EV, Dancause N, Taylor MD, Nudo RJ (2007) VEGF protein associates to neurons in remote regions following cortical infarct. J Cereb Blood Flow Metab 27:76–85CrossRefPubMed
go back to reference Stowe AM, Plautz EJ, Nguyen P, Frost SB, Eisner-Janowicz I, Barbay S, Dancause N, Sensarma A, Taylor MD, Zoubina EV, Nudo RJ (2008) Neuronal HIF-1 alpha protein and VEGFR-2 immunoreactivity in functionally related motor areas following a focal M1 infarct. J Cereb Blood Flow Metab 28:612–620CrossRefPubMed Stowe AM, Plautz EJ, Nguyen P, Frost SB, Eisner-Janowicz I, Barbay S, Dancause N, Sensarma A, Taylor MD, Zoubina EV, Nudo RJ (2008) Neuronal HIF-1 alpha protein and VEGFR-2 immunoreactivity in functionally related motor areas following a focal M1 infarct. J Cereb Blood Flow Metab 28:612–620CrossRefPubMed
go back to reference Taguchi A, Nakagomi N, Matsuyama T, Kikuchi-Taura A, Yoshikawa H, Kasahara Y, Hirose H, Moriwaki H, Nakagomi T, Soma T, Stern DM, Naritomi H (2009) Circulating CD34-positive cells have prognostic value for neurologic function in patients with past cerebral infarction. J Cereb Blood Flow Metab 29:34–38CrossRefPubMed Taguchi A, Nakagomi N, Matsuyama T, Kikuchi-Taura A, Yoshikawa H, Kasahara Y, Hirose H, Moriwaki H, Nakagomi T, Soma T, Stern DM, Naritomi H (2009) Circulating CD34-positive cells have prognostic value for neurologic function in patients with past cerebral infarction. J Cereb Blood Flow Metab 29:34–38CrossRefPubMed
go back to reference Tian HL, Chen H, Cui YH, Xu T, Zhou LF (2007) Increased protein and mRNA expression of endostatin in the ishemic brain tissue of rabbits after middle cerebral artery occlusion. Neurosci Bull 23:35–40CrossRefPubMed Tian HL, Chen H, Cui YH, Xu T, Zhou LF (2007) Increased protein and mRNA expression of endostatin in the ishemic brain tissue of rabbits after middle cerebral artery occlusion. Neurosci Bull 23:35–40CrossRefPubMed
go back to reference U.S. National Institutes of Health (2009) NIH Stroke Scale (NIHSS). American U.S. National Institutes of Health (2009) NIH Stroke Scale (NIHSS). American
go back to reference van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJ, van Gijn J (1988) Interobserver agreement for the assessment of handicap in stroke patients. Stroke 19:604–607CrossRefPubMed van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJ, van Gijn J (1988) Interobserver agreement for the assessment of handicap in stroke patients. Stroke 19:604–607CrossRefPubMed
go back to reference Walia A, Yang JF, Huang YH, Rosenblatt MI, Chang JH, Azar DT (2015) Endostatin’s emerging roles in angiogenesis lymphangiogenesis, disease, and clinical applications. Biochim Biophys Acta 1850:2422–2438CrossRefPubMedPubMedCentral Walia A, Yang JF, Huang YH, Rosenblatt MI, Chang JH, Azar DT (2015) Endostatin’s emerging roles in angiogenesis lymphangiogenesis, disease, and clinical applications. Biochim Biophys Acta 1850:2422–2438CrossRefPubMedPubMedCentral
go back to reference Wang HB, Yang L, Wu J, Sun L, Wu J, Tian H, Weisel RD, Li RK (2014) Reduced ischemic injury after stroke in mice by angiogenic gene delivery via ultrasound-targeted microbubble destruction. J Neuropathol Exp Neurol 73:548–558CrossRefPubMed Wang HB, Yang L, Wu J, Sun L, Wu J, Tian H, Weisel RD, Li RK (2014) Reduced ischemic injury after stroke in mice by angiogenic gene delivery via ultrasound-targeted microbubble destruction. J Neuropathol Exp Neurol 73:548–558CrossRefPubMed
go back to reference Yang JP, Liu HJ, Liu XF (2010) VEGF promotes angiogenesis and functional recovery in stroke rats. J Investig Surg 23:149–155CrossRef Yang JP, Liu HJ, Liu XF (2010) VEGF promotes angiogenesis and functional recovery in stroke rats. J Investig Surg 23:149–155CrossRef
go back to reference Zhao YH, Yuan B, Chen J, Feng DH, Zhao B, Qin C, Chen YF (2013) Endothelial progenitor cells: therapeutic perspective for ischemic stroke. CNS Neurosci Ther 19:67–75CrossRefPubMed Zhao YH, Yuan B, Chen J, Feng DH, Zhao B, Qin C, Chen YF (2013) Endothelial progenitor cells: therapeutic perspective for ischemic stroke. CNS Neurosci Ther 19:67–75CrossRefPubMed
Metadata
Title
Changes in serum vascular endothelial growth factor and endostatin concentrations associated with circulating endothelial progenitor cells after acute ischemic stroke
Authors
Lixia Xue
Hao Chen
Ting Zhang
Jingjiong Chen
Zhi Geng
Yuwu Zhao
Publication date
01-04-2017
Publisher
Springer US
Published in
Metabolic Brain Disease / Issue 2/2017
Print ISSN: 0885-7490
Electronic ISSN: 1573-7365
DOI
https://doi.org/10.1007/s11011-017-9953-z

Other articles of this Issue 2/2017

Metabolic Brain Disease 2/2017 Go to the issue