Vol 76, No 3 (2017)
Original article
Published online: 2017-02-14

open access

Page views 1478
Article views/downloads 1086
Get Citation

Connect on Social Media

Connect on Social Media

The expression of inhibitor of nuclear factor kappa-B kinase epsilon (IKKe) in human aortic aneurysm

L. Zhang1, L. Wang, W. Chen, Y. Xu, L. Wang, R. Iskandar, Y. Wang, X. Chen
Pubmed: 28198528
Folia Morphol 2017;76(3):372-378.

Abstract

Background: Aortic aneurysm (AA) is one of the most common causes of sudden death among elderly people. Although AA can be detected by non-invasive imaging techniques, there are no pharmacological treatments currently available to prevent progression at any stage of the disease. In this study we will explore the expression of inhibitor of nuclear factor kappa-B kinase epsilon (IKKe) in AA and its potential underlying molecular mechanism in AA.

Materials and methods: Human aortic tissue was taken from 14 patients who underwent surgical repair of AA for the AA group and another 11 patients with normal aorta who underwent aortic valve replacement surgery for the control group. After excision, we used haematoxylin-eosin staining, Masson staining, immunohistochemistry analysis and Western blot analysis to observe the expres­sion, location and morphological changes of the IKKe, P50 and the extracellular matrix within the AA.

Results: In the AA group, haematoxylin-eosin staining revealed a loss of medial integrity and inflammatory cell infiltration. Masson staining confirmed the degradation of the extracellular matrix in the AA group. Immunohistochemistry analysis showed increased infiltration of inflammatory cells and up-regulation of proinflammatory cytokines in the AA group when compared to the control group. Based on immunohistochemistry and Western blot analysis, there was clearly over-expression of IKKe, P50 and MMP2 in AA group, mainly in the intrinsic aortic cells of the media.

Conclusions: The over-expression of IKKe may play an important role in the ori­gination and progression of AA and might be a vital target for their treatment.

Article available in PDF format

View PDF Download PDF file

References

  1. Cao C, Zhu Y, Chen W, et al. IKKepsilon knockout prevents high fat diet induced arterial atherosclerosis and NF-κB signaling in mice. PLoS One. 2013; 8(5): e64930.
  2. Cheuk BLY, Cheng SWK. Can local secretion of prostaglandin E2, thromboxane B2, and interleukin-6 play a role in ruptured abdominal aortic aneurysm? World J Surg. 2008; 32(1): 55–61.
  3. Golledge J, Muller J, Daugherty A, et al. Abdominal aortic aneurysm: pathogenesis and implications for management. Arterioscler Thromb Vasc Biol. 2006; 26(12): 2605–2613.
  4. Hinterseher I, Erdman R, Elmore JR, et al. Novel pathways in the pathobiology of human abdominal aortic aneurysms. Pathobiology. 2013; 80(1): 1–10.
  5. Jones KG, Brull DJ, Brown LC, et al. Interleukin-6 (IL-6) and the prognosis of abdominal aortic aneurysms. Circulation. 2001; 103(18): 2260–2265.
  6. Kim YW, West XZ, Byzova TV. Inflammation and oxidative stress in angiogenesis and vascular disease. J Mol Med (Berl). 2013; 91(3): 323–328.
  7. Lenk GM, Tromp G, Weinsheimer S, et al. Whole genome expression profiling reveals a significant role for immune function in human abdominal aortic aneurysms. BMC Genomics. 2007; 8: 237.
  8. Löffek S, Schilling O, Franzke CW. Series "matrix metalloproteinases in lung health and disease": Biological role of matrix metalloproteinases: a critical balance. Eur Respir J. 2011; 38(1): 191–208.
  9. Nagase H, Visse R, Murphy G. Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res. 2006; 69(3): 562–573.
  10. Rohde LE, Arroyo LH, Rifai N, et al. Plasma concentrations of interleukin-6 and abdominal aortic diameter among subjects without aortic dilatation. Arterioscler Thromb Vasc Biol. 1999; 19(7): 1695–1699.
  11. Svensjö S, Björck M, Gürtelschmid M, et al. Low prevalence of abdominal aortic aneurysm among 65-year-old Swedish men indicates a change in the epidemiology of the disease. Circulation. 2011; 124(10): 1118–1123.
  12. Thompson RW. Reflections on the pathogenesis of abdominal aortic aneurysms. Cardiovasc Surg. 2002; 10(4): 389–394.
  13. Tsai SH, Huang PH, Peng YJ, et al. Zoledronate attenuates angiotensin II-induced abdominal aortic aneurysm through inactivation of Rho/ROCK-dependent JNK and NF-kappaB pathway. Cardiovasc Res. 2013; 100(3): 501–510.
  14. Verhelst K, Verstrepen L, Carpentier I, et al. IkappaB kinase epsilon (IKKepsilon): a therapeutic target in inflammation and cancer. Biochem Pharmacol. 2013; 85(7): 873–880.
  15. Yamashita O, Yoshimura K, Nagasawa A, et al. Periostin links mechanical strain to inflammation in abdominal aortic aneurysm. PLoS One. 2013; 8(11): e79753.
  16. Yoshimura K, Aoki H. Recent advances in pharmacotherapy development for abdominal aortic aneurysm. Int J Vasc Med. 2012; 2012: 648167.