Mierzejewska, P.; Di Marzo, N.; Zabielska-Kaczorowska, M.A.; Walczak, I.; Slominska, E.M.; Lavitrano, M.; Giovannoni, R.; Kutryb-Zajac, B.; Smolenski, R.T. Endothelial Effects of Simultaneous Expression of Human HO-1, E5NT, and ENTPD1 in a Mouse. Pharmaceuticals2023, 16, 1409.
Mierzejewska, P.; Di Marzo, N.; Zabielska-Kaczorowska, M.A.; Walczak, I.; Slominska, E.M.; Lavitrano, M.; Giovannoni, R.; Kutryb-Zajac, B.; Smolenski, R.T. Endothelial Effects of Simultaneous Expression of Human HO-1, E5NT, and ENTPD1 in a Mouse. Pharmaceuticals 2023, 16, 1409.
Mierzejewska, P.; Di Marzo, N.; Zabielska-Kaczorowska, M.A.; Walczak, I.; Slominska, E.M.; Lavitrano, M.; Giovannoni, R.; Kutryb-Zajac, B.; Smolenski, R.T. Endothelial Effects of Simultaneous Expression of Human HO-1, E5NT, and ENTPD1 in a Mouse. Pharmaceuticals2023, 16, 1409.
Mierzejewska, P.; Di Marzo, N.; Zabielska-Kaczorowska, M.A.; Walczak, I.; Slominska, E.M.; Lavitrano, M.; Giovannoni, R.; Kutryb-Zajac, B.; Smolenski, R.T. Endothelial Effects of Simultaneous Expression of Human HO-1, E5NT, and ENTPD1 in a Mouse. Pharmaceuticals 2023, 16, 1409.
Abstract
The vascular endothelium is key target for immune, and thrombotic responses that has to be controlled in successful xenotransplantation. Several genes were identified that if induced or overexpressed help to regulate the inflammatory response and preserve the transplanted organ function and metabolism. However, few studies addressed combined expression of such genes. The aim of this work was to evaluate in vivo the effects of the simultaneous expression of a three human genes in a mouse generated using the multi-cistronic F2A technology.
Male 3-month-old mice that express human heme oxygenase 1 (hHO-1), ecto-5’-nucleotidase (hE5NT), and ecto-nucleoside triphosphate diphosphohydrolase 1 (hENTPD1) (Transgenic) were compared to wild-type FVB mice (Control). Background analysis include extracellular nucleotide catabolism enzymes profile on the aortic surface, blood nucleotide concentration and serum L-arginine metabolites. Furthermore, inflammatory stress induced by LPS in transgenic and control mice was used to characterize interleukin 6 (IL-6) and adhesion molecules endothelium permeabil-ity responses.
Transgenic mice had significantly higher rates of extracellular adenosine triphosphate and adenosine monophosphate hydrolysis on the aortic surface in comparison to control. Increased levels of blood AMP and adenosine were also noticed in transgenics. Moreover, transgenic ani-mals demonstrated the decrease in serum monomethyl-L-arginine level and a higher L-arginine/ monomethyl-L-arginine ratio. Importantly, significantly decreased serum IL-6, and adhesion mol-ecule levels were observed in transgenic mice in comparison to control after LPS treatment. Fur-thermore, reduced endothelial permeability in the LPS-treated transgenic mice was noted as com-pared to LPS-treated control.
The human enzymes (hHO-1, hE5NT, hENTPD1) simultaneously encoded in transgenic mice demonstrated benefits in sev-eral biochemical and functional aspects of endothelium. This is consistent in use of this approach in the context of xenotransplantation.
Medicine and Pharmacology, Cardiac and Cardiovascular Systems
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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