Role of myeloperoxidase in abdominal aortic aneurysm formation: Mitigation by taurine

Ha Won Kim, Andra L. Blomkalns, Mourad Ogbi, Manesh Thomas, Daniel Gavrila, Bonnie S. Neltner, Lisa A. Cassis, Robert W. Thompson, Robert M. Weiss, Paul D. Lindower, Victor M. Blanco, Michael L. McCormick, Alan Daugherty, Xiaoming Fu, Stanley L. Hazen, Brian Kevin Stansfield, Yuqing Huo, David J Fulton, Tapan Kumar Chatterjee, Neal Lee Weintraub

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Oxidative stress plays a fundamental role in abdominal aortic aneurysm (AAA) formation. Activated polymorphonuclear leukocytes (or neutrophils) are associated with AAA and express myeloperoxidase (MPO), which promotes inflammation, matrix degradation, and other pathological features of AAA, including enhanced oxidative stress through generation of reactive oxygen species. Both plasma and aortic MPO levels are elevated in patients with AAA, but the role of MPO in AAA pathogenesis has, heretofore, never been investigated. Here, we show that MPO gene deletion attenuates AAA formation in two animal models: ANG II infusion in apolipoprotein E-deficient mice and elastase perfusion in C57BL/6 mice. Oral administration of taurine [1% or 4% (wt/vol) in drinking water], an amino acid known to react rapidly with MPO-generated oxidants like hypochlorous acid, also prevented AAA formation in the ANG II and elastase models as well as the CaCl2 application model of AAA formation while reducing aortic peroxidase activity and aortic protein-bound dityrosine levels, an oxidative cross link formed by MPO. Both MPO gene deletion and taurine supplementation blunted aortic macrophage accumulation, elastin fragmentation, and matrix metalloproteinase activation, key features of AAA pathogenesis. Moreover, MPO gene deletion and taurine administration significantly attenuated the induction of serum amyloid A, which promotes ANG II-induced AAAs. These data implicate MPO in AAA pathogenesis and suggest that studies exploring whether taurine can serve as a potential therapeutic for the prevention or treatment of AAA in patients merit consideration. NEW & NOTEWORTHY Neutrophils are abundant in abdominal aortic aneurysm (AAA), and myeloperoxidase (MPO), prominently expressed in neutrophils, is associated with AAA in humans. This study demonstrates that MPO gene deletion or supplementation with the natural product taurine, which can scavenge MPO-generated oxidants, can prevent AAA formation, suggesting an attractive potential therapeutic strategy for AAA.

Original languageEnglish (US)
Pages (from-to)H1168-H1179
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume313
Issue number6
DOIs
StatePublished - Dec 1 2017

Fingerprint

Taurine
Abdominal Aortic Aneurysm
Peroxidase
Gene Deletion
Neutrophils
Oxidants
Oxidative Stress
Hypochlorous Acid
Serum Amyloid A Protein
Elastin
Pancreatic Elastase
Apolipoproteins E
Biological Products
Matrix Metalloproteinases
Inbred C57BL Mouse
Drinking Water
Oral Administration

Keywords

  • Abdominal aortic aneurysm
  • Angiotensin II
  • Calcium chloride
  • Elastase
  • Myeloperoxidase
  • Taurine

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Role of myeloperoxidase in abdominal aortic aneurysm formation : Mitigation by taurine. / Kim, Ha Won; Blomkalns, Andra L.; Ogbi, Mourad; Thomas, Manesh; Gavrila, Daniel; Neltner, Bonnie S.; Cassis, Lisa A.; Thompson, Robert W.; Weiss, Robert M.; Lindower, Paul D.; Blanco, Victor M.; McCormick, Michael L.; Daugherty, Alan; Fu, Xiaoming; Hazen, Stanley L.; Stansfield, Brian Kevin; Huo, Yuqing; Fulton, David J; Chatterjee, Tapan Kumar; Weintraub, Neal Lee.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 313, No. 6, 01.12.2017, p. H1168-H1179.

Research output: Contribution to journalArticle

Kim, HW, Blomkalns, AL, Ogbi, M, Thomas, M, Gavrila, D, Neltner, BS, Cassis, LA, Thompson, RW, Weiss, RM, Lindower, PD, Blanco, VM, McCormick, ML, Daugherty, A, Fu, X, Hazen, SL, Stansfield, BK, Huo, Y, Fulton, DJ, Chatterjee, TK & Weintraub, NL 2017, 'Role of myeloperoxidase in abdominal aortic aneurysm formation: Mitigation by taurine', American Journal of Physiology - Heart and Circulatory Physiology, vol. 313, no. 6, pp. H1168-H1179. https://doi.org/10.1152/ajpheart.00296.2017
Kim, Ha Won ; Blomkalns, Andra L. ; Ogbi, Mourad ; Thomas, Manesh ; Gavrila, Daniel ; Neltner, Bonnie S. ; Cassis, Lisa A. ; Thompson, Robert W. ; Weiss, Robert M. ; Lindower, Paul D. ; Blanco, Victor M. ; McCormick, Michael L. ; Daugherty, Alan ; Fu, Xiaoming ; Hazen, Stanley L. ; Stansfield, Brian Kevin ; Huo, Yuqing ; Fulton, David J ; Chatterjee, Tapan Kumar ; Weintraub, Neal Lee. / Role of myeloperoxidase in abdominal aortic aneurysm formation : Mitigation by taurine. In: American Journal of Physiology - Heart and Circulatory Physiology. 2017 ; Vol. 313, No. 6. pp. H1168-H1179.
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AU - Gavrila, Daniel

AU - Neltner, Bonnie S.

AU - Cassis, Lisa A.

AU - Thompson, Robert W.

AU - Weiss, Robert M.

AU - Lindower, Paul D.

AU - Blanco, Victor M.

AU - McCormick, Michael L.

AU - Daugherty, Alan

AU - Fu, Xiaoming

AU - Hazen, Stanley L.

AU - Stansfield, Brian Kevin

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