单位：[1]Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, USA[2]Department of Pathology, China-Japan Friendship Hospital, Beijing, China[3]Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, China[4]Department of Cancer Biology, College of Medicine, University of Cincinnati, Cincinnati, Ohio. USA[5]Department of Cardiac Surgery, University of Michigan Medical Center, Ann Arbor, Michigan, USA.
Abdominal aortic aneurysm (AAA) is a life-threatening degenerative vascular disease. Endothelial cell (EC) dysfunction is implicated in AAA. Our group recently demonstrated that Kruppel-like factor 11 (KLF11) plays an essential role in maintaining vascular homeostasis, at least partially through inhibition of EC inflammatory activation. However, the functions of endothelial KLF11 in AAA remain unknown. Here we found that endothelial KLF11 expression was reduced in the ECs from human aneurysms and was time dependently decreased in the aneurysmal endothelium from both elastase- and Pcsk9/AngII-induced AAA mouse models. KLF11 deficiency in ECs markedly aggravated AAA formation, whereas EC-selective KLF11 overexpression markedly inhibited AAA formation. Mechanistically, KLF11 not only inhibited the EC inflammatory response but also diminished MMP9 expression and activity and reduced NADPH oxidase 2-mediated production of reactive oxygen species in ECs. In addition, KLF11-deficient ECs induced smooth muscle cell dedifferentiation and apoptosis. Overall, we established endothelial KLF11 as a potentially novel factor protecting against AAA and a potential target for intervention in aortic aneurysms.
基金：
NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [HL138139, HL068878, HL134569, HL122664, HL145176, HL150233]; American Heart AssociationAmerican Heart Association [20P0ST35110064, 18PRE34000005]
第一作者单位：[1]Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, USA
通讯作者：
通讯机构：[1]Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, USA[5]Department of Cardiac Surgery, University of Michigan Medical Center, Ann Arbor, Michigan, USA.[*1]Department of Internal Medicine, University of Michigan Medical Center, NCRC Bldg26-357S, 2800 Plymouth Road, Ann Arbor, Michigan 48109, USA[*2]Department of Internal Medicine, University of Michigan Medical Center, NCRC Bldg26-361S, 2800 Plymouth Road, Ann Arbor, Michigan 48109, USA
推荐引用方式(GB/T 7714)：
Zhao Guizhen,Chang Ziyi,Zhao Yang,et al.KLF11 protects against abdominal aortic aneurysm through inhibition of endothelial cell dysfunction[J].JCI INSIGHT.2021,6(5):doi:10.1172/jci.insight.141673.
APA：
Zhao, Guizhen,Chang, Ziyi,Zhao, Yang,Guo, Yanhong,Lu, Haocheng...&Zhang, Jifeng.(2021).KLF11 protects against abdominal aortic aneurysm through inhibition of endothelial cell dysfunction.JCI INSIGHT,6,(5)
MLA：
Zhao, Guizhen,et al."KLF11 protects against abdominal aortic aneurysm through inhibition of endothelial cell dysfunction".JCI INSIGHT 6..5(2021)
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