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Open Access Research article

Clinical significance of plasma VEGF value in ischemic stroke - research for biomarkers in ischemic stroke (REBIOS) study

Ryu Matsuo1*, Tetsuro Ago1*, Masahiro Kamouchi1, Junya Kuroda1, Takahiro Kuwashiro1, Jun Hata2, Hiroshi Sugimori1, Kenji Fukuda4, Seiji Gotoh2, Noriko Makihara3, Masayo Fukuhara2, Hideto Awano5, Tetsu Isomura5, Kazuo Suzuki5, Masahiro Yasaka3, Yasushi Okada3, Yutaka Kiyohara2 and Takanari Kitazono1

Author Affiliations

1 Department of Medicine and Clinical Science, Kyushu University, 3-1-1 Maidashi, higashi-ku, Fukuoka, 812-8582, Japan

2 Environmental Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, higashi-ku, Fukuoka, Japan

3 Department of Cerebrovascular Medicine, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama, chuo-ku, Fukuoka, Japan

4 Department of Cerebrovascular Disease, St Mary’s Hospital, 422 tsubukuhonmachi, Kurume, Japan

5 Molecuence Corporation, 1000 Kamoshidamachi, aoba-ku, Yokohama, Japan

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BMC Neurology 2013, 13:32  doi:10.1186/1471-2377-13-32

Published: 8 April 2013



Vascular endothelial growth factor (VEGF) is a well-known molecule mediating neuronal survival and angiogenesis. However, its clinical significance in ischemic stroke is still controversial. The goal of this study was to examine the temporal profile of plasma VEGF value and its clinical significance in ischemic stroke with taking its subtypes into consideration.


We prospectively enrolled 171 patients with ischemic stroke and age- and gender-matched healthy subjects. The stroke patients were divided into 4 subtypes: atherothrombotic infarction (ATBI, n = 34), lacunar infarction (LAC, n = 45), cardioembolic infarction (CE, n = 49) and other types (OT, n = 43). Plasma VEGF values were measured as a part of multiplex immunoassay (Human MAP v1.6) and we obtained clinical information at 5 time points (days 0, 3, 7, 14 and 90) after the stroke onset.


Plasma VEGF values were significantly higher in all stroke subtypes but OT than those in the controls throughout 90 days after stroke onset. There was no significant difference in the average VEGF values among ATBI, LAC, and CE. VEGF values were positively associated with neurological severity in CE patients, while a negative association was found in ATBI patients. After adjustment for possible confounding factors, plasma VEGF value was an independent predictor of poor functional outcome in CE patients.


Although plasma VEGF value increases immediately after the stroke onset equally in all stroke subtypes, its significance in functional outcome may be different among the stroke subtypes.

Brain infarction; Vascular endothelial growth factor (VEGF); National Institute of health stroke scale (NIHSS); Functional outcome; Modified rankin scale (mRS)