Journal article
Role of myeloperoxidase in abdominal aortic aneurysm formation: mitigation by taurine
American journal of physiology. Heart and circulatory physiology, Vol.313(6), pp.H1168-H1179
12/01/2017
DOI: 10.1152/ajpheart.00296.2017
PMCID: PMC5814655
PMID: 28971841
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 CaCl
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.
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.
Details
- Title: Subtitle
- Role of myeloperoxidase in abdominal aortic aneurysm formation: mitigation by taurine
- Creators
- Ha Won Kim - Division of Cardiology, Department of Medicine, Medical College of Georgia at Augusta University, Augusta, GeorgiaAndra L Blomkalns - Department of Emergency Medicine, Medical College of Georgia at Augusta University, Augusta, GeorgiaMourad Ogbi - Division of Cardiology, Department of Medicine, Medical College of Georgia at Augusta University, Augusta, GeorgiaManesh Thomas - Division of Cardiovascular Medicine, University of Iowa, Iowa City, IowaDaniel Gavrila - Division of Cardiovascular Medicine, University of Iowa, Iowa City, IowaBonnie S Neltner - Division of Cardiovascular Diseases, Department of Internal Medicine, University of Cincinnati, Cincinnati, OhioLisa A Cassis - Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KentuckyRobert W Thompson - Department of Surgery, Washington University School of Medicine, St. Louis, MissouriRobert M Weiss - Division of Cardiovascular Medicine, University of Iowa, Iowa City, IowaPaul D Lindower - Division of Cardiovascular Medicine, University of Iowa, Iowa City, IowaVictor M Blanco - Division of Cardiovascular Diseases, Department of Internal Medicine, University of Cincinnati, Cincinnati, OhioMichael L McCormick - Department of Radiation Oncology, University of Iowa, Iowa City, IowaAlan Daugherty - Departmentof Physiology and Saha Cardiovascular Research Center, University of Kentucky, Lexington, Kentucky; andXiaoming Fu - Department of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OhioStanley L Hazen - Department of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OhioBrian K Stansfield - Department of Pediatrics, Medical College of Georgia at Augusta University, Augusta, GeorgiaYuqing Huo - Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, Augusta, GeorgiaDavid J Fulton - Department of Pharmacology and Toxicology, Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, GeorgiaTapan Chatterjee - Division of Cardiology, Department of Medicine, Medical College of Georgia at Augusta University, Augusta, GeorgiaNeal L Weintraub - Division of Cardiology, Department of Medicine, Medical College of Georgia at Augusta University, Augusta, Georgia; nweintraub@augusta.edu
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Heart and circulatory physiology, Vol.313(6), pp.H1168-H1179
- DOI
- 10.1152/ajpheart.00296.2017
- PMID
- 28971841
- PMCID
- PMC5814655
- ISSN
- 0363-6135
- eISSN
- 1522-1539
- Grant note
- S10 OD016346 / NIH HHS R01 HL126949 / NHLBI NIH HHS R01 HL112640 / NHLBI NIH HHS R01 HL134934 / NHLBI NIH HHS
- Language
- English
- Date published
- 12/01/2017
- Academic Unit
- Radiology; Cardiovascular Medicine; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984094534402771
Metrics
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