KLF11 protects against abdominal aortic aneurysm through inhibition of endothelial cell dysfunction
| Autor: | Ziyi Chang, Guizhen Zhao, Tianqing Zhu, Minerva T. Garcia-Barrio, Yanhong Guo, Huilun Wang, Haocheng Lu, Wenying Liang, Jifeng Zhang, Yanbo Fan, Bo Yang, Oren Rom, Y. Eugene Chen, Jinjian Sun, Yang Zhao, Lin Chang |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Male endocrine system Endothelium Apoptosis Vascular biology Cell Line 03 medical and health sciences Mice 0302 clinical medicine medicine Animals Humans cardiovascular diseases chemistry.chemical_classification Reactive oxygen species NADPH oxidase biology Vascular disease business.industry Elastase Endothelial Cells General Medicine Cell Dedifferentiation medicine.disease Cardiovascular disease Abdominal aortic aneurysm Endothelial stem cell Mice Inbred C57BL Repressor Proteins 030104 developmental biology medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis biology.protein Cancer research cardiovascular system Medicine business Apoptosis Regulatory Proteins Aortic Aneurysm Abdominal Research Article |
| Zdroj: | JCI Insight, Vol 6, Iss 5 (2021) JCI Insight |
| ISSN: | 2379-3708 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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