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Reviews in Cardiovascular Medicine  2019, Vol. 20 Issue (4): 201-208     DOI: 10.31083/j.rcm.2019.04.57
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AGE-RAGE stress play a role in aortic aneurysm: A comprehensive review and novel potential therapeutic target
Kailash Prasad1, *()
1 Department of Physiology (APP), College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada, S7N 5E5, Canada
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Aortic aneurysms are mostly asymptomatic but have high rates of mortality when there is rupture or dissection. Matrix metalloproteinases is involved in the evolution of aortic aneurysms. Advanced glycation end products and its cell receptor RAGE (receptor for AGE) and sRAGE (soluble receptor of AGE) have been suggested to be involved in the pathogenesis of numerous diseases. This review addresses the role of AGE, RAGE and AGE-RAGE stress (AGE/sRAGE) in the pathogenesis of abdominal aortic aneurysm and thoracic aortic aneurysm in humans. AGE-RAGE interaction not only increases the generation of reactive oxygen species and inflammatory cytokines, but also activates NF-kB. There are increases in the levels of AGE in aortic tissue, skin and serum in patients with thoracic aortic aneurysm and abdominal aortic aneurysm. Levels of RAGE in tissue are elevated in abdominal aortic aneurysm. AGE-RAGE stress is elevated in patients with thoracic aortic aneurysm. The serum levels of cytokines and Matrix metalloproteinases are elevated in patients with thoracic aortic aneurysm and abdominal aortic aneurysm. The levels of AGE and AGE-RAGE stress correlate positively with cytokines and Matrix metalloproteinases, but the serum levels of sRAGE correlate negatively with cytokines and Matrix metalloproteinases. Cytokines levels are positively correlated with the levels of Matrix metalloproteinases in patients with thoracic aortic aneurysm. In conclusion, elevated levels of AGE, RAGE and AGE-RAGE stress, and reduced levels of sRAGE increase the levels of cytokines that in turn increase the production of Matrix metalloproteinases resulting in formation of aortic aneurysms. The data suggest that AGE-RAGE stress is involved in the pathogenesis of aortic aneurysms. Treatment options have also been discussed.

Key words:  Aortic aneurysms      AGE      RAGE      AGE-RAGE stress      cytokines      matrix metalloproteinase     
Submitted:  25 October 2019      Accepted:  14 November 2019      Published:  30 December 2019     
*Corresponding Author(s):  Kailash Prasad     E-mail:

Cite this article: 

Kailash Prasad. AGE-RAGE stress play a role in aortic aneurysm: A comprehensive review and novel potential therapeutic target. Reviews in Cardiovascular Medicine, 2019, 20(4): 201-208.

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Figure 1.  Schematic diagram of involvement of AGE-RAGE stress in the development of aortic aneurysm. AGE, advanced glycation end products; RAGE, receptor for advanced glycation end products; sRAGE, soluble receptor for advanced glycation end products; GLO- 1,glyoxalase-1; GLO-2, glyoxalase-2; AGER1, advanced glycation end products receptor 1; AGER 2, advanced glycation end products receptor-2; MMPs, matrix metalloproteinases.; (↑)increase; (↓), decrease.

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