Vascular endothelial growth factor increases in serum and protects against the organ injuries in severe acute pancreatitis.
BACKGROUND
We have demonstrated that apoptosis was detected in liver and kidney cells in severe acute pancreatitis and that cellular injury because of apoptosis may be involved in the mechanism of multiple organ dysfunction syndrome. Vascular endothelial growth factor (VEGF) is a glycoprotein with potent angiogenic, mitogenic, and vascular permeability-enhancing activities specific for endothelial cells. It has been reported that VEGF is implicated in many diseases such as cancer and inflammation.


METHODS
Serum VEGF concentrations were determined in patients with acute pancreatitis at the time of admission, and the relationships with severity, blood biochemical parameters on admission, organ dysfunction during the clinical course, and prognosis were analyzed. Moreover, to clarify the role of VEGF in acute pancreatitis, effects of VEGF were investigated in experimental severe acute pancreatitis.


RESULTS
Serum VEGF levels were significantly elevated in patients with acute pancreatitis. Serum VEGF levels were not related to severity or prognosis. In male patients, among the various blood biochemical parameters, serum lactate dehydrogenase, and blood urea nitrogen levels were positively correlated with serum VEGF levels. Serum VEGF levels with organ dysfunction (liver and kidney) were higher than those without organ dysfunction. In rat experimental severe acute pancreatitis, serum VEGF levels were significantly elevated. Recombinant VEGF did not affect the lung water content, volume of ascitic fluid, hematocrit, or serum amylase, but improved the hepatic and renal dysfunctions. Apoptosis of liver and kidney was significantly inhibited by the administration of VEGF.


CONCLUSIONS
These results suggest that VEGF is closely related to organ dysfunction in severe acute pancreatitis, and that VEGF may function as not a vascular permeability factor, but a protective factor via the anti-apoptotic effect against the organ injuries in this disease.
Department of Gastroenterological Surgery, Kobe University Graduate School of Medical Sciences, Kobe, Japan. uedataka@med.kobe-u.ac.jp
Takashi
T
Ueda
Yoshifumi
Y
Takeyama
Takeo
T
Yasuda
Naoki
N
Matsumura
Hidehiro
H
Sawa
Takahiro
T
Nakajima
Yoshikazu
Y
Kuroda
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis; D001202:Ascitic Fluid; D004195:Disease Models, Animal; D015633:Extravascular Lung Water; D005260:Female; D006400:Hematocrit; D006801:Humans; D020287:In Situ Nick-End Labeling; D007668:Kidney / Q000473:pathology; D008099:Liver / Q000473:pathology; D008297:Male; D009102:Multiple Organ Failure / Q000517:prevention & control*; D010195:Pancreatitis / Q000097:blood* / Q000150:complications* / Q000473:pathology; D011379:Prognosis; D051381:Rats; D017208:Rats, Wistar; D042461:Vascular Endothelial Growth Factor A / Q000097:blood* / Q000502:physiology*
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A