Details
- Autor(en) / Beteiligte
- Titel
- Plasmid-based transient human stromal cell-derived factor-1 gene transfer improves cardiac function in chronic heart failure
- Ist Teil von
- Gene therapy, 2011-09, Vol.18 (9), p.867-873
- Ort / Verlag
- London: Nature Publishing Group
- Erscheinungsjahr
- 2011
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- We previously demonstrated that transient stromal cell-derived factor-1 alpha (SDF-1) improved cardiac function when delivered via cell therapy in ischemic cardiomyopathy at a time remote from acute myocardial infarction (MI) rats. We hypothesized that non-viral gene transfer of naked plasmid DNA-expressing hSDF-1 could similarly improve cardiac function. To optimize plasmid delivery, we tested SDF-1 and luciferase plasmids driven by the cytomegalovirus (CMV) promoter with (pCMVe) or without (pCMV) translational enhancers or α myosin heavy chain (pMHC) promoter in a rodent model of heart failure. In vivo expression of pCMVe was 10-fold greater than pCMV and pMHC expression and continued over 30 days. We directly injected rat hearts with SDF-1 plasmid 1 month after MI and assessed heart function. At 4 weeks after plasmid injection, we observed a 35.97 and 32.65% decline in fractional shortening (FS) in control (saline) animals and pMHC-hSDF1 animals, respectively, which was sustained to 8 weeks. In contrast, we observed a significant 24.97% increase in animals injected with the pCMVe-hSDF1 vector. Immunohistochemistry of cardiac tissue revealed a significant increase in vessel density in the hSDF-1-treated animals compared with control animals. Increasing SDF-1 expression promoted angiogenesis and improved cardiac function in rats with ischemic heart failure along with evidence of scar remodeling with a trend toward decreased myocardial fibrosis. These data demonstrate that stand-alone non-viral hSDF-1 gene transfer is a strategy for improving cardiac function in ischemic cardiomyopathy.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0969-7128eISSN: 1476-5462DOI: 10.1038/gt.2011.18Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3169804
- Format
- –
- Schlagworte
- Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy, Angiogenesis, Animals, Applied cell therapy and gene therapy, Biological and medical sciences, Biotechnology, Care and treatment, Cell differentiation, maturation, development, hematopoiesis, Cell physiology, Chemokine CXCL12 - genetics, Chronic Disease, Cytomegalovirus, Fundamental and applied biological sciences. Psychology, Gene therapy, Gene Transfer Techniques, Genetic Therapy - methods, Genetic Vectors - metabolism, Health aspects, Health. Pharmaceutical industry, Heart failure, Heart Failure - genetics, Heart Failure - physiopathology, Heart Failure - therapy, Industrial applications and implications. Economical aspects, Luciferase, Medical sciences, Molecular and cellular biology, Myocardial Infarction - therapy, Myocardial Ischemia - therapy, Myocardium, Neovascularization, Physiologic, Original, Physiological aspects, Plasmids, Prevention, Promoter Regions, Genetic, Rats, Rats, Inbred Lew, Rodents, Stromal Cells - metabolism, Time Factors, Transfusions. Complications. Transfusion reactions. Cell and gene therapy