title: AAV2/8-humanFOXP3 gene therapy shows robust anti-atherosclerosis efficacy in LDLR-KO mice on high cholesterol diet.
abstract: 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.
authors.affiliation: Central Arkansas Veterans Healthcare System, 111J, 4300 West 7th Street, Little Rock, AR, 72205, USA. MCao@uams.edu.
authors.forename: M
authors.initials: M
authors.lastname: Cao
authors.affiliation: Central Arkansas Veterans Healthcare System, 111J, 4300 West 7th Street, Little Rock, AR, 72205, USA. Sue.theus@va.gov.
authors.forename: S A
authors.initials: SA
authors.lastname: Theus
authors.affiliation: Central Arkansas Veterans Healthcare System, 111J, 4300 West 7th Street, Little Rock, AR, 72205, USA. Karl.Straub@va.gov.
authors.forename: K D
authors.initials: KD
authors.lastname: Straub
authors.affiliation: Kiromic LLC, Lubbock, TX, USA. joseonc@gmail.com.
authors.forename: J A
authors.initials: JA
authors.lastname: Figueroa
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Texas Tech University Health Sciences Center, School of Medicine, Lubbock, TX, 79415, USA. leonardo.mirandola@gmail.com.
authors.forename: L
authors.initials: L
authors.lastname: Mirandola
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Texas Tech University Health Sciences Center, School of Medicine, Lubbock, TX, 79415, USA. mchiriva@gmail.com.|Kiromic LLC, Lubbock, TX, USA. mchiriva@gmail.com.
authors.forename: M
authors.initials: M
authors.lastname: Chiriva-Internati
authors.affiliation: Central Arkansas Veterans Healthcare System, 111J, 4300 West 7th Street, Little Rock, AR, 72205, USA. plhermonat@uams.edu.
authors.forename: P L
authors.initials: PL
authors.lastname: Hermonat
mesh_terms: D000818:Animals; D001011:Aorta / Q000000981:diagnostic imaging / Q000473:pathology; D050197:Atherosclerosis / Q000097:blood / Q000503:physiopathology / Q000628:therapy*; D002791:Cholesterol, Dietary / Q000097:blood*; D000229:Dependovirus; D004032:Diet; D051858:Forkhead Transcription Factors / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000235:genetics*; D050378:T-Lymphocytes, Regulatory; D019076:Transgenes; D014463:Ultrasonography
chemical_list: D002791:Cholesterol, Dietary; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D011973:Receptors, LDL