Role of myeloperoxidase in abdominal aortic aneurysm formation: mitigation by taurine
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Dec 01, 2017
- Source ID
- 10.1152/ajpheart.00296.2017
Entities
People
- Alan Daugherty
- Andra L. Blomkalns
- Bonnie S. Neltner
- Brian K. Stansfield
- Daniel Gavrila
- David J. Fulton
- Ha Won Kim
- Lisa A. Cassis
- Manesh Thomas
- Michael L. Mccormick
- Mourad Ogbi
- Neal L. Weintraub
- Paul D. Lindower
- Robert M. Weiss
- Robert W. Thompson
- Stanley L. Hazen
- Tapan Chatterjee
- Victor M. Blanco
- Xiaoming Fu
- Yuqing Huo
Organizations
- Augusta University
- Cleveland Clinic
- Medical College of Georgia
- National Heart, Lung, and Blood Institute
- United States Department of Defense
- University of Cincinnati
- University of Iowa
- University of Kentucky
- Washington University in St. Louis