AAV2/8-humanFOXP3 gene therapy shows robust anti-atherosclerosis efficacy in LDLR-KO mice on high cholesterol diet
| Autor: | Maohua Cao, Paul L. Hermonat, Leonardo Mirandola, K D Straub, S A Theus, Maurizio Chiriva-Internati, Jose A. Figueroa |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
medicine.medical_specialty Normal diet Genetic enhancement Inflammation Gene delivery Biology T-Lymphocytes Regulatory General Biochemistry Genetics and Molecular Biology Cholesterol Dietary chemistry.chemical_compound Mice Internal medicine medicine Animals Humans Transgenes Aorta Ultrasonography Medicine(all) Mice Knockout Cholesterol Biochemistry Genetics and Molecular Biology(all) Research FOXP3 Forkhead Transcription Factors General Medicine Genetic Therapy Dependovirus Atherosclerosis Diet Endocrinology chemistry Receptors LDL Knockout mouse LDL receptor Immunology medicine.symptom |
| Zdroj: | Journal of Translational Medicine |
| ISSN: | 1479-5876 |
| Popis: | Inflammation is a key etiologic component in atherogenesis. Previously we demonstrated that adeno-associated virus (AAV) 2/8 gene delivery of Netrin1 inhibited atherosclerosis in the low density lipoprotein receptor knockout mice on high-cholesterol diet (LDLR-KO/HCD). One important finding from this study was that FOXP3 was strongly up-regulated in these Netrin1-treated animals, as FOXP3 is an anti-inflammatory gene, being the master transcription factor of regulatory T cells. These results suggested that the FOXP3 gene might potentially be used, itself, as an agent to limit atherosclerosis. To test this hypothesis AAV2/8 (AAV)/hFOXP3 or AAV/Neo (control) gene therapy virus were tail vein injected into the LDLR-KO/HCD animal model. It was found that hFOXP3 gene delivery was associated with significantly lower HCD-induced atherogenesis, as measured by larger aortic lumen cross sectional area, thinner aortic wall thickness, and lower aortic systolic blood velocity compared with Neo gene-HCD-treated controls. Moreover these measurements taken from the hFOXP3/HCD-treated animals very closely matched those measurements taken from the normal diet (ND) control animals. These data strongly suggest that AAV/hFOXP3 delivery gave a robust anti-atherosclerosis therapeutic effect and further suggest that FOXP3 be examined more stringently as a therapeutic gene for clinical use. |
| Databáze: | OpenAIRE |
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