Premium
Exogenous vascular endothelial growth factor delivery prior to endothelial precursor cell transplantation in orthotopic liver transplantation–induced hepatic ischemia/reperfusion injury
Author(s) -
Cao Ding,
Wang Menghao,
Gong Junhua,
Wei Sidong,
Gong Jianping,
Li Jinzheng
Publication year - 2017
Publication title -
liver transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.814
H-Index - 150
eISSN - 1527-6473
pISSN - 1527-6465
DOI - 10.1002/lt.24745
Subject(s) - vascular endothelial growth factor , angiogenesis , medicine , transplantation , hepatocyte growth factor , vascular endothelial growth factor a , growth factor , endocrinology , reperfusion injury , placental growth factor , cancer research , immunology , ischemia , receptor , vegf receptors
Vascular endothelial growth factor (VEGF) promotes angiogenesis in vivo. We hypothesized that exogenous delivery of VEGF prior to bone marrow–derived endothelial precursor cell (EPC) transplantation may improve orthotopic liver transplantation (OLT)–induced hepatic ischemia/reperfusion injury (HIRI). OLT between Sprague Dawley donor rats and inbred LEW Wistar recipient rats was performed in 6 experimental groups to comparatively assess the effects of the VEGF gene: an untreated normal control group, a surgical control group, a liposomal control group, a VEGF group receiving only the liposome‐encapsulated VEGF plasmid, an EPC group receiving only EPCs, and an EPC+VEGF group receiving the liposome‐encapsulated VEGF plasmid followed by EPCs. VEGF plasmid delivery to liver tissue, endogenous VEGF, and vascular endothelial growth factor receptor (VEGFR) expression, liver transaminase levels, hepatocellular injury levels, apoptosis, apoptotic biomarkers, hepatotrophic mitogens, angiogenesis, and nitric oxide synthase (NOS) activity were assayed after OLT. Exogenous VEGF gene delivery prior to EPC transplantation significantly increased endogenous VEGF and VEGFR expression, significantly reduced liver transaminase levels, significantly reduced hepatocellular injury levels, significantly reduced hepatic apoptosis levels, and significantly reduced several apoptotic biomarkers (ie, B cell lymphoma 2–associated X protein/B cell lymphoma 2 ratio, caspase 3 activity, and heat shock protein 70 expression) in post‐OLT–induced HIRI. Moreover, VEGF gene delivery prior to EPC transplantation significantly increased hepatotrophic mitogen expression (ie, epidermal growth factor, heparin‐binding epidermal growth factor–like growth factor, hepatocyte growth factor, and transforming growth factor α), angiogenesis, and NOS activity in post‐OLT–induced HIRI. In conclusion, exogenous liposomal delivery of the VEGF gene prior to bone marrow–derived EPC transplantation may be an effective strategy in decreasing OLT‐induced HIRI. Liver Transplantation 23 804–812 2017 AASLD.