Expression of biologically active atrial natriuretic factor following intrahepatic injection of a replication-defective adenoviral vector in dogs
| Autor: | Isabelle Deprez, Moez Saana, Serge Adnot, Daniel W. Rosenberg, Valérie Chetboul, Isabelle Pham, François Crespeau, Jean-Louis Pouchelon, Micheline Adam, Andreja Ambriovic, Marc Eloit |
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| Jazyk: | angličtina |
| Rok vydání: | 1999 |
| Předmět: |
Male
medicine.medical_specialty DNA Complementary medicine.medical_treatment Genetic Vectors Gene delivery Biology Adenoviridae Cell Line Viral vector Dogs Internal medicine Complementary DNA Genetics medicine otorhinolaryngologic diseases Animals Humans Luciferases Molecular Biology DNA Primers Rous sarcoma virus Base Sequence Drug Administration Routes Defective Viruses Biological activity biology.organism_classification adenovirus atrial natriuretic factor intrahepatic injection Long terminal repeat Endocrinology Liver embryonic structures cardiovascular system Molecular Medicine Diuretic Atrial Natriuretic Factor hormones hormone substitutes and hormone antagonists Hormone |
| Popis: | Atrial natriuretic factor (ANF) is a potent natriuretic, diuretic, and vasoactive hormone produced and released by atrial cardiomyocytes, We investigated whether adenovirus-mediated ANF gene delivery to dogs leads to a sustained increase in circulating ANF levels resulting in long-lasting biological effects. An adenoviral vector containing the canine ANF cDNA under the control of the Rous sarcoma virus 3' long terminal repeat (AdRSV-ANF) was injected via the intrahepatic route to nonvaccinated 2-month-old dogs. In the first group of four dogs injected with AdRSV-ANF (10(10.2) TCID50), a short-lived increase in plasma ANF concentrations not associated with biological effects occurred 8-10 days after the injection, as compared with four control dogs injected with an adenovirus encoding a luciferase reporter gene (AdRSV-luc), In a second series of experiments, six dogs received AdRSV-ANF at a dose of 10(10) TCID50 and a replication-defective type 5 adenovirus harboring a modified VAI gene (Ad-VAr) at the same dose. Sustained increases in plasma ANF concentrations and urinary cGMP excretion starting on day 2 and persisting until day 20 were seen, as well as concomitant elevations in natriuresis and diuresis, a transient increase in cardiac output, and a delay in body weight gain, as compared with control dogs injected with AdRSV-luc/Ad-VAr. These results show that adenovirus-mediated ANF gene expression can lead to systemic biological effects in dogs, a finding of potential relevance for the treatment of cardiovascular diseases and sodium-retaining disorders. |
| Databáze: | OpenAIRE |
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