Vascular Endothelial Growth Factor Production in Peritoneal Macrophages of Cirrhotic Patients: Regulation by Cytokines and Bacterial Lipopolysaccharide

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Abstract
Vascular endothelial growth factor (VEGF) is an angiogenic peptide with vascular permeability and relaxing properties. This study assessed whether peritoneal macrophages of cirrhotic patients can be up–regulated to produce VEGF under proper stimulatory conditions. Macrophages were isolated from ascites. VEGF protein secretion and mRNA expression were measured in basal conditions and after stimulation with lipopolysaccharide (LPS), tumor necrosis factor α (TNF–α), and interleukin–1 (IL–1). These substances induced a time– and dose–dependent increase in both VEGF production and transcript expression. Assays with actinomycin D showed that VEGF mRNA induction is secondary to both higher VEGF gene transcription and mRNA stability. Ascites and plasma concentration of VEGF was also measured in cirrhotic patients with (n = 15) and without (n = 10) spontaneous bacterial peritonitis (SBP). Plasma values did not differ between both groups of patients. However, ascites VEGF levels were higher in SBP patients than in noninfected cirrhotic patients (710 ± 183 vs. 94 ± 15 pg/mL; P < .025). These results indicate that cytokines and LPS markedly increase VEGF protein secretion and mRNA expression in macrophages of cirrhotic patients, and suggest that this substance could be an important mediator of the pronounced arterial vasodilation frequently occurring in SBP patients
Funding Information
  • Dirección General de Investigación Científica y Técnica ((SAF99-0016))
  • M. Pérez-Ruiz received a postfellowship grant from Hospital Clínic. M. Morales-Ruiz received a grant from Fundació Privada Clínic per la Recerca Biomèdica, and P. Cejudo received a grant from IDIBAPS