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Angiogenesis within the duodenum of patients with cirrhosis is modulated by mechanosensitive K ruppel‐like factor 2 and micro RNA ‐126
Author(s) -
Kobus Karolina,
Kopycinska Justyna,
KozlowskaWiechowska Anna,
Urasinska Elzbieta,
KempinskaPodhorodecka Agnieszka,
Haas Tara L.,
Milkiewicz Piotr,
Milkiewicz Malgorzata
Publication year - 2012
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2012.02791.x
Subject(s) - angiogenesis , cirrhosis , vascular endothelial growth factor , messenger rna , neovascularization , medicine , western blot , duodenum , pathology , cancer research , endocrinology , chemistry , vegf receptors , gene , biochemistry
Background The mechanism involved in neovascularization in splanchnic circulation and the main trigger that induces angiogenesis in patients with cirrhosis are not fully recognized. Aims To explore the involvement of flow sensitive lung K ruppel‐like factor ( KLF 2), microRNA‐126 (mi R ‐126), angiopoietin‐2 ( A ng‐2) and heme oxygenase‐1 ( HO ‐1) in modulation of vascular endothelial growth factor ( VEGF ) signalling that have a critical effect on growth of new blood vessels. Methods Duodenal biopsies from 22 patients with cirrhosis and 10 controls were obtained during routine endoscopy. The process of angiogenesis was evaluated by a measurement of CD 31 concentration, immunodetection of CD 34 protein and estimation of capillary densities. Messenger RNA (mRNA) and protein expressions were analysed by real‐time PCR , W estern blot or ELISA respectively. Results Markers of angiogenesis (both, CD 31 and CD 34) were significantly enhanced in cirrhotic patients. In comparison to healthy controls, levels of A ng‐2 and KLF ‐2 m RNA s as well as A ng‐2, KLF ‐2, HO ‐1, VEGF protein expressions were considerably increased. Levels of s CD 163, a surrogate marker of portal hypertension, correlated with levels of A ng‐2, ( P = 0.021) and VEGF ( P = 0.009). The expression of mi R ‐126, a KLF 2‐mediated regulator of the VEGF signalling was enhanced in cirrhotic patients. Conclusions Our results demonstrate, for the first time in humans, that neovascularization is induced in duodenal tissue of patients with cirrhosis and proangiogenic factors such as KLF ‐2, A ng‐2, mi R ‐126 and VEGF can contribute to the angiogenesis induced by hemodynamic forces. Thus, cirrhosis‐induced blood flow and pressure within splanchnic vessels may be important hemodynamic triggers that initiate the angiogenic signalling cascade.