I-κB kinase-ε knockout protects against angiotensin II induced aortic valve thickening in apolipoprotein E deficient mice
Aortic stenosis (AS) is considered to be an actively regulated progress that involves similar pathophysiological processes as atherosclerosis. I-κB kinase-ε (IKKε) is a proinflammatory molecule involved in atherosclerosis. The objective of the present study was to define the role of IKKε in patholog...
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doaj-e82c0b6d13a84a709c3f4798fbdab0e82021-05-21T04:15:53ZengElsevierBiomedicine & Pharmacotherapy0753-33222019-01-0110912871295I-κB kinase-ε knockout protects against angiotensin II induced aortic valve thickening in apolipoprotein E deficient miceShuai He0Fulai Nian1Wen Chen2Li Yin3Merveesh L. Auchoybur4Zhonghao Tao5Shaowen Tang6Xin Chen7Department of Thoracic and Cardiovascular Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, ChinaDepartment of Thoracic and Cardiovascular Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, ChinaDepartment of Thoracic and Cardiovascular Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, ChinaDepartment of Thoracic and Cardiovascular Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, ChinaDepartment of Thoracic and Cardiovascular Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, ChinaDepartment of Thoracic and Cardiovascular Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, ChinaDepartment of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, ChinaDepartment of Thoracic and Cardiovascular Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, China; Corresponding author.Aortic stenosis (AS) is considered to be an actively regulated progress that involves similar pathophysiological processes as atherosclerosis. I-κB kinase-ε (IKKε) is a proinflammatory molecule involved in atherosclerosis. The objective of the present study was to define the role of IKKε in pathological valvular remodeling. Aortic valves (AVs) from 52 patients undergoing AV replacement (AS) and 13 patients undergoing heart transplant (Control) were analyzed. ApoE−/− mice (AK, n = 20) and ApoE−/−IKKε-/− mice (DK, n = 20) were generated and infused with saline or Ang II for 4 weeks. We found an upregulation of IKKε in human stenotic aortic valves compared to that in control AVs. Our results demonstrated that AK mice receiving AngII exhibited more advanced valvular remodeling and markedly increased IKKε expression. Conversely, loss of IKKε reduced adverse aortic valve thickening in response to Ang II, as measured by histological analyses. Furthermore, according to immunofluorescence analysis, Ang II resulted in obvious increases in the expression of α-SMA, TGF-β and NF-κB pathway components in the AK group, especially in the thickened area, while these increases were blocked in the DK group. Moreover, IKKε was co-expressed with α-SMA in valvular interstitial cells in ApoE−/− mice after an AngII infusion. These data provide evidence that IKKε plays a key role in the development of valvular remodeling and that it may be a novel target for the treatment of AS.http://www.sciencedirect.com/science/article/pii/S0753332218336473Aortic stenosisI-κB kinase-εAngiotensin IIValveValvular remodeling |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shuai He Fulai Nian Wen Chen Li Yin Merveesh L. Auchoybur Zhonghao Tao Shaowen Tang Xin Chen |
spellingShingle |
Shuai He Fulai Nian Wen Chen Li Yin Merveesh L. Auchoybur Zhonghao Tao Shaowen Tang Xin Chen I-κB kinase-ε knockout protects against angiotensin II induced aortic valve thickening in apolipoprotein E deficient mice Biomedicine & Pharmacotherapy Aortic stenosis I-κB kinase-ε Angiotensin II Valve Valvular remodeling |
author_facet |
Shuai He Fulai Nian Wen Chen Li Yin Merveesh L. Auchoybur Zhonghao Tao Shaowen Tang Xin Chen |
author_sort |
Shuai He |
title |
I-κB kinase-ε knockout protects against angiotensin II induced aortic valve thickening in apolipoprotein E deficient mice |
title_short |
I-κB kinase-ε knockout protects against angiotensin II induced aortic valve thickening in apolipoprotein E deficient mice |
title_full |
I-κB kinase-ε knockout protects against angiotensin II induced aortic valve thickening in apolipoprotein E deficient mice |
title_fullStr |
I-κB kinase-ε knockout protects against angiotensin II induced aortic valve thickening in apolipoprotein E deficient mice |
title_full_unstemmed |
I-κB kinase-ε knockout protects against angiotensin II induced aortic valve thickening in apolipoprotein E deficient mice |
title_sort |
i-κb kinase-ε knockout protects against angiotensin ii induced aortic valve thickening in apolipoprotein e deficient mice |
publisher |
Elsevier |
series |
Biomedicine & Pharmacotherapy |
issn |
0753-3322 |
publishDate |
2019-01-01 |
description |
Aortic stenosis (AS) is considered to be an actively regulated progress that involves similar pathophysiological processes as atherosclerosis. I-κB kinase-ε (IKKε) is a proinflammatory molecule involved in atherosclerosis. The objective of the present study was to define the role of IKKε in pathological valvular remodeling. Aortic valves (AVs) from 52 patients undergoing AV replacement (AS) and 13 patients undergoing heart transplant (Control) were analyzed. ApoE−/− mice (AK, n = 20) and ApoE−/−IKKε-/− mice (DK, n = 20) were generated and infused with saline or Ang II for 4 weeks. We found an upregulation of IKKε in human stenotic aortic valves compared to that in control AVs. Our results demonstrated that AK mice receiving AngII exhibited more advanced valvular remodeling and markedly increased IKKε expression. Conversely, loss of IKKε reduced adverse aortic valve thickening in response to Ang II, as measured by histological analyses. Furthermore, according to immunofluorescence analysis, Ang II resulted in obvious increases in the expression of α-SMA, TGF-β and NF-κB pathway components in the AK group, especially in the thickened area, while these increases were blocked in the DK group. Moreover, IKKε was co-expressed with α-SMA in valvular interstitial cells in ApoE−/− mice after an AngII infusion. These data provide evidence that IKKε plays a key role in the development of valvular remodeling and that it may be a novel target for the treatment of AS. |
topic |
Aortic stenosis I-κB kinase-ε Angiotensin II Valve Valvular remodeling |
url |
http://www.sciencedirect.com/science/article/pii/S0753332218336473 |
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