Recombinant VEGF-C (Cys156Ser) improves mesenteric lymphatic drainage and gut immune surveillance in experimental cirrhosis

Background and AimLymphatic vessels (LVs) are crucial for maintaining abdominal fluid homeostasis immunity. In cirrhosis, mesenteric LVs (mLVs) dilated dysfunctional. Given the established role of VEGF-C in improving LVs, we hypothesized that treatment could ameliorate functions mLVs cirrhosis.MethodIn this study, developed a nanoformulation comprising LV-specific growth-factor, recombinant human VEGF-C(Cys156Ser) protein, (E-VEGF-C) delivered it orally different models rat cirrhosis to target mLVs. Cirrhotic rats were given without served as vehicles. Drainage was analyzed using tracer dye. Portal systemic physiological assessments computed-tomography performed measure portal pressures ascites. Gene expression permeability primary lymphatic endothelial cells (LyECs) studied. Immune lymph nodes (MLNs) quantified by flow-cytometry. Endogenous exogenous gut bacterial translocation MLNs examined.ResultsIn cirrhotic rats, leaky with impaired drainage. Treatment E-VEGF-C induced proliferation mLVs, reduced their diameter improved functional Ascites significantly compared vehicle. animals, CD8+CD134+ T-cells increased while CD25+Treg-cells decreased. Both endogenous limited levels endotoxins ascites blood comparison upregulated VE-Cad LyECs functionally these cells.ConclusionE-VEGF-C ameliorates drainage, pressure, strengthens cytotoxic immunity experimental cirrhosis. It may thus serve promising therapy manage reduce pathogenic cirrhosis.Lay SummaryA pro-lymphangiogenic growth factor, VEGF-C, encapsulated nanolipocarriers liver facilitate its vessel uptake. administration attenuating animal models. only load ascitic endotoxins. holds potential pressure also patients