Jiancong Ren1, Yanshuo Han2, Tongming Ren3, Hong Fang4, Xiaohan Xu5, Yu Lun1, Han Jiang1, Shijie Xin1, Jian Zhang1. 1. Department of Vascular & Thyroid Surgery, the First Hospital, China Medical University. 2. Department of General Surgery, Shengjing Hospital, China Medical University. 3. Department of Anatomy Laboratory, Xinxiang Medical College. 4. Department of Pancreatic Surgery, the First Hospital, China Medical University. 5. Department of Anesthesiology, the First Hospital, China Medical University.
Abstract
AIM: Inflammation plays a significant role in the pathogenesis of human abdominal aortic aneurysm (AAA). AEBP1 can promote activation of the NF-κB pathway, subsequently affecting the expression of NF-κB target genes, including inflammatory cytokines and matrix metalloproteinases (MMPs). Our objective was to examine the role of AEBP1 in the development of AAA and characterize the underlying mechanism. METHODS: ITRAQ, RT-PCR, western blot, immunohistochemistry, and ELISA were used to compare different experimental groups with the controls and to determine the differentially expressed genes. We generated an AAA model using porcine pancreatic elastase in Sprague-Dawley rats and silenced their AEBP1 in vivo by adenoviruses injected intra-adventitially. We also silenced or overexpressed AEBP1 in human vascular smooth muscle cells in vitro in the presence and in the absence of NF-κB inhibitor BAY 11-7082. RESULTS: Proteome iTRAQ revealed a high expression of AEBP1 in AAA patients, which was verified by qRT-PCR, western blot, immunohistochemistry, and ELISA. The mean expression level of AEBP1 in AAA patients was higher than that in controls. Along with AEBP1 upregulation, we also verified mis-activation of NF-κB in human AAA samples. The in vivo studies indicated that AEBP1 knockdown suppressed AAA progression. Finally, the in vitro studies illustrated that AEBP1 promotes activation of the NF-κB pathway, subsequently upregulating pro-inflammatory factors and MMPs. CONCLUSIONS: Our results indicate a role of AEBP1 in the pathogenesis of AAA and provide a novel insight into how AEBP1 causes the development of AAA by activating the NF-κB pathway.
AIM: Inflammation plays a significant role in the pathogenesis of humanabdominal aortic aneurysm (AAA). AEBP1 can promote activation of the NF-κB pathway, subsequently affecting the expression of NF-κB target genes, including inflammatory cytokines and matrix metalloproteinases (MMPs). Our objective was to examine the role of AEBP1 in the development of AAA and characterize the underlying mechanism. METHODS: ITRAQ, RT-PCR, western blot, immunohistochemistry, and ELISA were used to compare different experimental groups with the controls and to determine the differentially expressed genes. We generated an AAA model using porcine pancreatic elastase in Sprague-Dawley rats and silenced their AEBP1 in vivo by adenoviruses injected intra-adventitially. We also silenced or overexpressed AEBP1 in human vascular smooth muscle cells in vitro in the presence and in the absence of NF-κB inhibitor BAY 11-7082. RESULTS: Proteome iTRAQ revealed a high expression of AEBP1 in AAApatients, which was verified by qRT-PCR, western blot, immunohistochemistry, and ELISA. The mean expression level of AEBP1 in AAApatients was higher than that in controls. Along with AEBP1 upregulation, we also verified mis-activation of NF-κB in humanAAA samples. The in vivo studies indicated that AEBP1 knockdown suppressed AAA progression. Finally, the in vitro studies illustrated that AEBP1 promotes activation of the NF-κB pathway, subsequently upregulating pro-inflammatory factors and MMPs. CONCLUSIONS: Our results indicate a role of AEBP1 in the pathogenesis of AAA and provide a novel insight into how AEBP1 causes the development of AAA by activating the NF-κB pathway.
Authors: Debra L Rateri; Deborah A Howatt; Jessica J Moorleghen; Richard Charnigo; Lisa A Cassis; Alan Daugherty Journal: Am J Pathol Date: 2011-07-19 Impact factor: 4.307