The Diminished Expression of Proangiogenic Growth Factors and Their Receptors in Gastric Ulcers of Cirrhotic Patients

Jiing-Chyuan Luo,Han-Chieh Lin,Ching-Liang Lu,Fa-Yauh Lee,Hui-Chun Huang,Ming-Chih Hou,Yen-Ling Peng,Kuang-Wei Huang,Ying-Wen Wang,Matias A Avila

doi:10.1371/journal.pone.0061426

Abstract

ObjectivesThe pathogenesis of the higher occurrence of peptic ulcer disease in cirrhotic patients is complex. Platelets can stimulate angiogenesis and promote gastric ulcer healing. We compared the expressions of proangiogenic growth factors and their receptors in the gastric ulcer margin between cirrhotic patients with thrombocytopenia and those of non-cirrhotic patients to elucidate possible mechanisms.MethodsEligible cirrhotic patients (n = 55) and non-cirrhotic patients (n = 55) who had gastric ulcers were enrolled. Mucosa from the gastric ulcer margin and non-ulcer areas were sampled and the mRNA expressions of the proangiogenic growth factors (vascular endothelial growth factor [VEGF], platelet derived growth factor [PDGF], basic fibroblast growth factor [bFGF]) and their receptors (VEGFR1, VEGFR2, PDGFRA, PDGFRB, FGFR1, FGFR2) were measured and compared. Platelet count and the expressions of these growth factors and their receptors were correlated with each other.ResultsThe two groups were comparable in terms of gender, ulcer size and infection rate of Helicobacter pylori. However, the cirrhotic group were younger in age, had a lower platelet count than those in the non-cirrhotic group (p<0.05). The cirrhotic patients had diminished mRNA expressions of PDGFB, VEGFR2, FGFR1, and FGFR2 in gastric ulcer margin when compared with those of the non-cirrhotic patients (p<0.05). Diminished expressions of PDGFB and VEGFR2, FGFR1, and FGFR2 were well correlated with the degree of thrombocytopenia in these cirrhotic patients (ρ>0.5, p<0.001).ConclusionsOur findings implied that diminished activity of proangiogenic factors and their receptors may contribute to the pathogenesis of gastric ulcers in cirrhotic patients.

Highlights

Previous studies have shown that cirrhotic patients have a higher prevalence of peptic ulcer disease (PUD) than the general population [1,2]
Several proangiogenic factors are stored in platelets, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor, and platelet derived growth factor (PDGF) [12]
There were no significant differences in the mRNA expressions of proangiogenic growth factors (VEGF, basic fibroblast growth factor (bFGF), PDGF) and their receptors (VEGFR1, VEGFR2, FGFR1, FGFR2, PDGFRA, PDGFRB) over the non-ulcer areas of gastric mucosa between the cirrhotic and non-cirrhotic groups (Table 3)

Summary

Introduction

Previous studies have shown that cirrhotic patients have a higher prevalence of peptic ulcer disease (PUD) than the general population [1,2]. Several proangiogenic factors are stored in platelets, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and platelet derived growth factor (PDGF) [12]. These growth factors are released into the ulcer base from platelets and activate and promote the formation of new blood vessels during the hemostasis phase of ulcer healing [13]. This is likely to account for the ability of platelets to stimulate angiogenesis and promote gastric ulcer

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Conclusion