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 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.

Taurine attenuates hepatic steatosis in a genetic model of fatty liver disease

“…The mice were fed standard rodent chow (NMF; Oriental Yeast Co. Ltd., Tokyo, Japan). Several studies were performed with 1% (w/v) taurine containing water (Kim et al, 2017;Li et al, 2019;Park et al, 2017). In the present study, mice were given 0.5% (w/v) or 2% (w/v) taurine in their drinking water for four weeks.…”

The Role of Myeloperoxidase in Biomolecule Modification, Chronic Inflammation, and Disease

“…This strategy is only likely to be successful when high concentrations of these ''scavengers'' can be achieved. One potential species is taurine, which is present in high concentrations within neutrophils (152), with supplementation with taurine shown to decrease macrophage infiltration, elastin fragmentation, and MMP activation associated with the overexpression of MPO in an in vivo model of abdominal aortic aneurysms (128). Similarly, some seleniumcontaining compounds can react rapidly with MPO-derived oxidants (36), with the resulting selenoxides able to be catalytically recycled by cellular reductants and antioxidant enzymes (37).…”

Antithrombotic therapy in abdominal aortic aneurysm: beneficial or detrimental?

“…Together, uPA and tPA result in the cleavage of plasminogen to plasmin resulting in the activation of released MMPs and transforming growth factor-b1, degradation of fibronectin, and cleavage of fibrin and resultant fibrinolysis in the luminal layer. Importantly, targeted disruption of MMP-9, 34 MPO, 35 uPA, 36 and proteases 33 attenuate the initiation of AAA in various animal models. Collectively, these molecules contribute to the inflammatory response and proteolytic injury of the arterial wall resulting in aortic thinning and expansion.…”

“…30 Furthermore, MPO and erythrocyte lysis and release of free heme and iron produce a pro-oxidant environment, which augments damage to the aorta and thrombus in addition to reducing the survivability of infiltrating protective cells. 21,35,37 Finally, association of exogenous weak pathogens, or commensal bacteria (eg, Porphyromonas gingivalis), is present in the aneurysm ILT, which may prevent wound healing via ongoing activation of platelets and repeated infiltration/activation of neutrophils via toll-like receptors. 21 P gingivalis and Streptococcus mutans have been identified in aneurysm tissue, and the increased presence of P gingivalis is associated with augmented aneurysm and a neutrophil-rich ILT in a rat model of AAA.…”