KLF11 protects against abdominal aortic aneurysm through inhibition of endothelial cell dysfunction

Guizhen Zhao; Ziyi Chang; Yang Zhao; Yanhong Guo; Haocheng Lu; Wenying Liang; Oren Rom; Huilun Wang; Jinjian Sun; Tianqing Zhu; Yanbo Fan; Lin Chang; Bo Yang; Minerva Garcia-Barrio; Eugene Chen; Jifeng Zhang

doi:10.1172/jci.insight.141673

Published January 28, 2021 - More info

View PDF

Abstract

Abdominal aortic aneurysm (AAA) is a life-threatening degenerative vascular disease. Endothelial cell (EC) dysfunction is implicated in AAA. Our group recently demonstrated that Krüppel-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 significantly 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 induce smooth muscle cell dedifferentiation and apoptosis. Overall, we established endothelial KLF11 as a novel factor protecting against AAA and a potential target for intervention in aortic aneurysms.

KLF11 protects against abdominal aortic aneurysm through inhibition of endothelial cell dysfunction

Guizhen Zhao,¹ Ziyi Chang,¹ Yang Zhao,¹ Yanhong Guo,¹ Haocheng Lu,¹ Wenying Liang,¹ Oren Rom,¹ Huilun Wang,¹ Jinjian Sun,¹ Tianqing Zhu,¹ Yanbo Fan,² Lin Chang,¹ Bo Yang,³ Minerva Garcia-Barrio,¹ Eugene Chen,¹ and Jifeng Zhang¹

Article tools

Metrics

Go to

KLF11 protects against abdominal aortic aneurysm through inhibition of endothelial cell dysfunction

Guizhen Zhao,1 Ziyi Chang,1 Yang Zhao,1 Yanhong Guo,1 Haocheng Lu,1 Wenying Liang,1 Oren Rom,1 Huilun Wang,1 Jinjian Sun,1 Tianqing Zhu,1 Yanbo Fan,2 Lin Chang,1 Bo Yang,3 Minerva Garcia-Barrio,1 Eugene Chen,1 and Jifeng Zhang1

Article tools

Metrics

Go to

Sign up for email alerts

Guizhen Zhao,¹ Ziyi Chang,¹ Yang Zhao,¹ Yanhong Guo,¹ Haocheng Lu,¹ Wenying Liang,¹ Oren Rom,¹ Huilun Wang,¹ Jinjian Sun,¹ Tianqing Zhu,¹ Yanbo Fan,² Lin Chang,¹ Bo Yang,³ Minerva Garcia-Barrio,¹ Eugene Chen,¹ and Jifeng Zhang¹