Comparison of Mean VEGF-A Expression Between Acute Ischemic Stroke Patients and Non-Ischemic Stroke Subject


  • Ismail Setyopranoto Department of Neurology, Faculty of Medicine, Universitas Gadjah Mada and Dr Sardjito General Hospital, Yogyakarta, Indonesia
  • Ahmad Hamim Sadewa Department of Biochemistry, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia
  • Samekto Wibowo Department of Neurology, Faculty of Medicine, Universitas Gadjah Mada and Dr Sardjito General Hospital, Yogyakarta, Indonesia
  • I Putu Eka Widyadharma Department of Neurology, Faculty of Medicine, Udayana University and Sanglah General Hospital, Bali, Indonesia



Acute ischemic stroke, Hypoxia, Expression, VEGF-A


BACKGROUND: Glucose and oxygen supply to neurons are disrupted during acute ischemic stroke, resulting in hypoxia. This event, in turn, activates the transcription of hypoxia-inducible factor (HIF-1), which is responsible for activating genes responsible for angiogenesis, including vascular endothelial growth factor (VEGF). VEGF and their receptor systems exert complex mechanisms of angiogenesis, including the stimulator, inhibitors, angiogenic and modulator. VEGF-A is the primary regulator of angiogenesis, both during physiological and pathological conditions. Nevertheless, the role of VEGF on the prognosis of hypoxia remains controversial.

AIM: The purpose of this study was to address if there is any difference between the mean expression of VEGF-A between acute ischemic patients and non-ischemic stroke subjects.

METHODS: This was an observational study with a cross-sectional design, the population in this research is the acute ischemic stroke patients and non-ischemic stroke subjects, which were admitted on Emergency Room and later treated in the Stroke Unit, Dr Sardjito General Hospital, Yogyakarta, Indonesia. Subjects were recruited using the purposive method, yielding a total of 64 subjects on both groups. Diagnosis of acute ischemic stroke was established using a head CT scan. Patients who meet the inclusion criteria and willing to participate in the study were asked to provide informed consent. Laboratory analysis was conducted during the first 24 hours after being treated at Stroke Unit, Dr Sardjito General Hospital, Yogyakarta, Indonesia, with venous blood was withdrawn VEGF-A levels between acute ischemic stroke and non-ischemic stroke subjects were subsequently compared. Categorical variables (including gender) were tested using either chi-square or Fisher exact test. Interval data was examined using student t-test if data distribution was normal.

RESULTS: As many as 35 acute ischemic stroke and 35 non-ischemic stroke patients were included in the study, among whom were 18 men (51.43%) and 17 women (48.57%) among stroke patients and 21 (60%) men and 14 (40%) women among subjects without stroke. The average of the subject's age on stroke and non-ischemic stroke group was 58.51 and 48.57 years old. VEGF-A levels were significantly higher in the non-stroke group (561.77 ± 377.92) compared with stroke group (397.78 ± 181.53) with p = 0.02.

CONCLUSION: expression of VEGF-A in acute ischemic stroke group was lower when compared with the non-stroke group.


Download data is not yet available.


Metrics Loading ...

Plum Analytics Artifact Widget Block


Ferrara N. Role of vascular endothelial growth factor in regulation of physiological angiogenesis. Am J Physiol Cell Physiol. 2001; 280:C1358-66. PMid:11350730

Isner JM, Vale PR, Symes JF, Losordo DW. Assessment of risks associated with cardiovascular gene therapy in human subjects. Circ Res. 2001; 89:389-90. PMid:11532899

Boegehold MA, Kotchen TA. Effect of dietary salt on the skeletal muscle microvasculature in Dahl rats. Hypertension. 1990; 15:420-6.

Gu JW, Adair TH. Hypoxia-induced expression of VEGF is reversible in myocardial vascular smooth muscle cells. Am J Physiol. 1997; 273(2 Pt 2):H628-33. PMid:9277477

Klekamp JG, Jarzecka K, Perkett EA. Exposure to hyperoxia decreases the expression of vascular endothelial growth factor and its receptors in adults rat lungs. Am J Pathol. 1999; 154:823-31.

Niki T, Iba S, Tokunou M, Yamada T, Matsuno Y, Hirohashi S. Expression of vascular endothelial growth factors A, B, C, and D and their relationships to lymph node status in lung adenocarcinoma. Clin Cancer Res. 2000; 6:2431-9. PMid:10873096

George ML, Tutton MG, Janssen F, Arnaoutz A, Abulafi AM, Eccles SA, Swift RI. VEGF-A, VEGF-C, and VEGF-D in colorectal cancer progression. Neoplasia. 2001; 3(5):420-7. PMid:11687953 PMCid:PMC1506210

Tang RF, Wang SX, Peng L, Wang SX, Zhang M, Li ZF, Zhang ZM, Xiao Y, Zhang FR. Expression of vascular endothelial growth factors A and C in human pancreatic cancer. World J Gastroenterol. 2006; 12(2):280-6. PMid:16482630 PMCid:PMC4066039

Schmidt M, Voelker HU, Kapp M, Dietl J, Kammerer U. Expression of VEGFR-1 (Flt-1) in breast cancer is associated with VEGF expression and with node-negative tumour stage. Anticancer Research. 2008; 28:1719-24. PMid:18630531

Engels K, du Bois A, Harter P, Fisseler-Eckhoff A, Kommoss F, Stauber R, Kaufmann M, Nekljudova V, Loibl S. VEGF-A, and i-NOS expression are prognostic factors in serous epithelial ovarian carcinomas after complete surgical resection. J Clin Pathol. 2009; 62:448-54. PMid:19126566

Davis JP, Wong AA, Schluter PJ, Henderson RD, O'Sullivan JD, Read SJ. Impact of premorbid undernutrition on outcome in stroke patients. Stroke. 2004; 35:1930-4. PMid:15218159

Katavetin P, Inagi R, Miyata T, Tanaka T, Sassa R, Ingelfinger JR, Fujita T, Nangaku M. Albumin suppresses vascular endothelial growth factor via alteration of hypoxia-inducible factor/hypoxia-responsive element pathway. Biochemical and biophysical research communications. 2008; 367(2):305-10. PMid:18155159

Dziedzic T, Pera J, Slowik A, Gryz-Kurek EA, Szczudlik A. Hypoalbuminemia in acute ischemic stroke patients: frequency and correlates. European Journal of Clinical Nutrition. 2007; 61:1318-22. PMid:17251921

Lerman, O.Z., Galiano, R.D., Armour, M., Levine, J.P., and Gurtner, G.C. Cellular dysfunction in the diabetic fibroblast: impairment in migration, vascular endothelial growth factor production, and response to hypoxia. Am J Pathol 2003; 162:303-12.

Oltmanns KM, Gehring H, Rudolf S, Schultes B, Rook S, Schweiger U, Born J, Fehm HL, Peters A. Hypoxia causes glucose intolerance in humans. Am J Respir Crit Care Med. 2004; 169:1231-7. PMid:15044204

Belgore FM, Blann AD, Li-Saw-Hee FL, Beevers DG, Lip GY. Plasma levels of vascular endothelial growth factor and its soluble receptor (SFlt-1) in essential hypertension. Am J Cardiol. 2001; 87: 805-7.

Mani N, Khaibullina A, Krum JM, Rosenstein JM. Activation of receptor-mediated angiogenesis and signaling pathways after VEGF administration in fetal rat CNS explants. J Cereb Blood Flow Metab. 2003; 23:1420-9. PMid:14663337

Esser S, Wolburg K, Wolburg H, Breier G, Kurzchalia T, Risau W. Vascular endothelial growth factor induces endothelial fenestrations in vitro. J Cell Biol. 1998; 140:947-59. PMid:9472045 PMCid:PMC2141756

Zhao L, Zhang MM, Ng KY. Effects of vascular permeability factor on the permeability of cultured endothelial cells from brain capillaries. J Cardiovasc Pharmacol. 1998; 32:1-4. PMid:9676713

Li L, Lundkvist A, Andersson D, Wilhelmsson U, Nagai N, Pardo AC, Nodin C, Stahlberg A, Aprico K, Larsson K, Yabe T, Moons L, Fotheringham A, Davies I, Carmeliet P, Schwartz JP, Pekna M, Kubista M, Blomstrand F, Maragakis N, Nilsson M, Pekny M. Protective role of reactive astrocytes in brain ischemia. Journal of Cerebral Blood Flow & Metabolism. 2007; 1:14.

Barreto GE, Sun X, Xu L, Giffard RG. Astrocyte proliferation following stroke in the mouse depends on distance from the infarct. PLoS ONE. 2011; 6(11):1-6. PMid:22132159 PMCid:PMC3221692

Mani N, Khaibullina A, Krum JM, Rosenstein JM. Astrocyte growth effects of vascular endothelial growth factor (VEGF) application to perinatal neocortical explants: receptor mediation and signal transduction pathways. Exp Neurol. 2005; 192:394-406. PMid:15755557

Chow J, Ogunshola O, Fan SY, Li Y, Ment LR, Madri JA. Astrocyte-derived VEGF mediates survival and tube stabilization of hypoxic brain microvascular endothelial cells in vitro. Brain Res Dev Brain Res. 2001; 130:123-32.

Fischer S, Wobben M, Kleinstuck J, Renz D, Schaper W. Effect of astroglial cells on hypoxia-induced permeability in PBMEC cells. Am J Physiol Cell Physiol. 2000; 279:C935-44. PMid:11003573

Rosenstein JM, Krum JM, Ruhrberg C. VEGF in the nervous system. Organogenesis. 2010; 6(2):107-14. PMid:20885857 PMCid:PMC2901814

Schratzberger P, Schratzberger G, Silver M, Curry C, Kearney M, Magner M, Alroy J, Adelman LS, Weinberg DH, Ropper AH, Isner JM. Favorable effect of VEGF gene transfer on ischemic peripheral neuropathy. Nat Med. 2000; 6:405-13. PMid:10742147

Zhang ZG, Zhang L, Jiang Q, Zhang R, Davies K, Powers C, Bruggen N, Chopp M. VEGF enhances angiogenesis and promotes blood brain barrier leakage in the ischemic brain. J Clin Invest. 2000; 106:829-38. PMid:11018070 PMCid:PMC517814

Sun Y, Jin K, Xie L, Childs J, Mao XO, Logvinova A, Greenberg DA. VEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral ischemia. J Clin Invest. 2003; 111:1843-51. PMid:12813020 PMCid:PMC161428

Krum JM, Khaibullina A. Inhibition of endogenous VEGF impedes revascularization and astroglial proliferation: Roles for VEGF in brain repair. Exp Neurol. 2003; 181:241-57.

Facchiano F, Fernandez E, Mancarella S, Maira G, Miscusi M, D'Arcangelo D, Cimino-Reale G, Falchetti ML, Capogrossi MC, Pallini R. Promotion of regeneration of corticospinal tract axons in rats with recombinant vascular endothelial growth factor alone and combined with adenovirus coding for this factor. J Neurosurg. 2002; 97:161-8. PMid:12134907

Widenfalk J, Lipson A, Jubran M, Hofstetter C, Ebendal T, Cao Y, Olson L. Vascular endothelial growth factor improves functional outcome and decreases secondary degeneration in experimental spinal cord contusion injury. Neuroscience. 2003; 120:951-60.

Hobson MI, Green CJ, Terenghi G. VEGF enhances intraneural angiogenesis and improves nerve regeneration after axotomy. J Anat. 2000; 197:591-605. PMid:11197533 PMCid:PMC1468175



How to Cite

Setyopranoto I, Sadewa AH, Wibowo S, Widyadharma IPE. Comparison of Mean VEGF-A Expression Between Acute Ischemic Stroke Patients and Non-Ischemic Stroke Subject. Open Access Maced J Med Sci [Internet]. 2019 Mar. 13 [cited 2022 May 19];7(5):747-51. Available from:



B - Clinical Sciences

Most read articles by the same author(s)

1 2 3 > >>