Serial measurement of vascular endothelial growth factor and transforming growth factor-beta 1 in serum of patients with acute ischemic stroke

Background and Purpose-Both vascular endothelial growth factor (VEGF) and t ransforming growth factor-beta 1 (TGF-beta 1) are expressed in higher than normal concentrations in the penumbra of patients after ischemic stroke. Be cause both cytokines are central to the processes of angiogenesis, tissue i nflammation, and fibrosis, we performed serial measurements of these cytoki nes in patients with cerebral infarction and determined their relationship to stroke etiology and volume. Methods-We serially (at days 0, 1, 3, 7, and 14) measured the serum levels of VEGF and active TGF-beta 1 in 29 patients with acute ischemic stroke. Ag e-matched healthy subjects (n=26) were used as controls. Results-Expression of VEGF was significantly increased in the majority of p atients after acute stroke at each of the time points compared with normal controls. Highest expression occurred at day 7 (588+/-121 pg/mL; P=0.005), and it remained significantly elevated at 14 days after stroke. Expression of VEGF correlated with infarct volume, clinical disability (Scandinavian S troke Scale), and peripheral leukocytosis and was significantly higher in p atients with atherothrombotic large-vessel disease and ischemic heart disea se (P<0.05 in all cases). In contrast, expression of active TGF-beta 1 was not significantly different from control patients at any of the measured ti me points. When the mean concentration of TGF-beta 1 from each patient (poo led time points) was compared with the control mean, a significant increase was found in only 2 patients, whereas levels decreased in 12 patients (P<0 .05). There was no correlation between circulating active TGF-beta 1 and VE GF expression, leukocytosis, stroke subtype, or patient disability as asses sed by Scandinavian Stroke Scale score. Conclusion-VEGF but not TGF-beta 1 showed a dramatic increase in serum of s troke patients. Correlation between stroke severity and VEGF concentration suggests it could be involved in the subsequent repair processes resulting in partial recovery after stroke. Correlation between VEGF expression and p eripheral leukocytosis suggests that these changes may also reflect the imm unologic status of the patient. VEGF may play an important role in the path ophysiology of acute ischemic stroke and could be of value in future treatm ent strategies.