title: KLF15 Overexpression Protects β-Aminopropionitrile-Induced Aortic Rupture in Rodent Model via Inhibiting Connective Tissue Growth Factor.
abstract: BackgroundKLF15 (Krüppel-like factor 15) was reported to be involved in a lot of cardiovascular diseases. Little is known about its role in initiation and development of aortic dissection (AD).MethodsSamples of the human aorta were collected during AD surgery and aortic valve replacement. Lentivirus was used for in vitro and in vivo KLF15 overexpression in BAPN (β-aminopropionitrile)-induced rat AD models. The survival times were recorded and compared between the two groups. Autopsy was used for confirming aorta rupture in rat models. qPCR analyses were used for detecting gene expression whereas Western blot and immunostaining were used for detecting protein expression when necessary.ResultsKLF15 expression was much lower in the aorta walls of AD group patients than the control group subjects. The survival curve showed that the survival time of AD models was prolonged after KLF15 overexpression. qPCR and Western blot showed that connective tissue growth factors (CTGFs) were significantly downregulated in the rat aortas. After KLF15 overexpression in aortic adventitial fibroblasts, the KLF15 mRNA was increased whereas CTGF and its target gene collagens I and III were downregulated. Immunofluorescence staining also showed a decrease in CTGF, collagen I, and III. Lenti-control did not induce a significant change of KLF15, CTGF, collagen I, and III expressions.ConclusionsKLF15 is involved in the mechanism of AD formation in human. Overexpression of KLF15 can partially rescue the aorta remodeling and AD formation in animal models. Our research highlighted a potential of KLF15 to serve as a new therapy target of AD.
authors.affiliation: Department of Cardio-thoracic Surgery, Xiangyang Central Hospital, Hubei University of Art and Science, Hubei Province, China.
authors.forename: Botao
authors.initials: B
authors.lastname: Zhan
authors.affiliation: Department of Cardio-thoracic Surgery, Xiangyang Central Hospital, Hubei University of Art and Science, Hubei Province, China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Cardio-thoracic Surgery, Xiangyang Central Hospital, Hubei University of Art and Science, Hubei Province, China.
authors.forename: Jiajun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Xiangyang Central Hospital, Hubei University of Art and Science, Hubei Province, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhu
authors.affiliation: Department of Cardio-thoracic Surgery, Xiangyang Central Hospital, Hubei University of Art and Science, Hubei Province, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Cardio-thoracic Surgery, Xiangyang Central Hospital, Hubei University of Art and Science, Hubei Province, China.
authors.forename: Junbo
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Cardio-thoracic Surgery, Xiangyang Central Hospital, Hubei University of Art and Science, Hubei Province, China.
authors.forename: Zengwang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Cardio-thoracic Surgery, Xiangyang Central Hospital, Hubei University of Art and Science, Hubei Province, China.
authors.forename: Ronghua
authors.initials: R
authors.lastname: Nie
mesh_terms: D000629:Aminopropionitrile; D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D001014:Aortic Aneurysm / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D001019:Aortic Rupture / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000378:metabolism*; D004108:Dilatation, Pathologic; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008297:Male; D009687:Nuclear Proteins / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation; D066253:Vascular Remodeling
chemical_list: C526316:CCN2 protein, rat; D024042:Collagen Type I; D024061:Collagen Type III; C414172:KLF15 protein, human; C520013:Klf15 protein, rat; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; D055513:Connective Tissue Growth Factor; D000629:Aminopropionitrile