KLF15 Overexpression Protects β-Aminopropionitrile-Induced Aortic Rupture in Rodent Model via Inhibiting Connective Tissue Growth Factor

• Published in: The Thoracic and cardiovascular surgeon Vol. 65; no. 2; p. 120
• Main Authors: Zhan, Botao, Hu, Zhipeng, Chen, Jiajun, Zhu, Rui, Zhao, Hua, Yang, Junbo, Zhang, Zengwang, Nie, Ronghua
• Format: Journal Article
• Language: English
• Published: Germany 01.03.2017
• Subjects: Aminopropionitrile; Animals; Aorta - metabolism; Aorta - pathology; Aortic Aneurysm - chemically induced; Aortic Aneurysm - genetics; Aortic Aneurysm - metabolism; Aortic Aneurysm - prevention & control; Aortic Rupture - chemically induced; Aortic Rupture - genetics; Aortic Rupture - metabolism; Aortic Rupture - prevention & control; Cells, Cultured; Collagen Type I - metabolism; Collagen Type III - metabolism; Connective Tissue Growth Factor - metabolism; Dilatation, Pathologic; Disease Models, Animal; Gene Transfer Techniques; Genetic Therapy - methods; Humans; Kruppel-Like Transcription Factors - biosynthesis; Kruppel-Like Transcription Factors - genetics; Kruppel-Like Transcription Factors - metabolism; Male; Nuclear Proteins - metabolism; Rats, Sprague-Dawley; Signal Transduction; Time Factors; Transfection; Up-Regulation; Vascular Remodeling
• ISSN: 1439-1902
• DOI: 10.1055/s-0035-1566743

KLF15 (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).  Samples 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.  KLF15 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.  KLF15 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.