P4551Myeloperoxidase activity aggravates aortic wall remodeling and participates in aneurysm development in Marfan Syndrome

Mehrkens, Dennis; Dohr, Johannes; Mollenhauer, Martin; Kochen, MM; Silva, A; Sengle, Gerhard; Rudolph, Volker; Klinke, Anna; Adam, Matti; Baldus, Stephan

doi:10.1093/eurheartj/ehy563.p4551

Cited by 4 publications

(2 citation statements)

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“…Increased MPO has been observed in aortic wall specimens from a mixed cohort of TAA patients [ 72 ]. Additionally, a MFS mouse model showed increased MPO expression in the aneurysmal aorta, along with increased MMP-2 and -9 expression, increased ECM fragmentation and apoptosis, increased 3-nitrotyrosine levels and increased ROS staining compared to wildtype [ 87 ]. Conversely, MPO-deficient MFS mice had no markers of ROS damage or MMP overexpression, preserved aortic architecture and smaller aneurysmal diameter.…”

Section: Sources Of Ros Imbalancementioning

confidence: 99%

Oxidative stress in genetically triggered thoracic aortic aneurysm: role in pathogenesis and therapeutic opportunities

et al. 2021

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Background: The primary objective of this review was to explore the contribution of oxidative stress to the pathogenesis of genetically-triggered thoracic aortic aneurysm (TAA). Genetically-triggered TAAs manifest substantial variability in onset, progression, and risk of aortic dissection, posing a significant clinical management challenge. There is a need for non-invasive biomarkers that predict the natural course of TAA and therapeutics that prevent aneurysm progression. Methods: An online systematic search was conducted within PubMed, MEDLINE, Scopus and ScienceDirect databases using keywords including: oxidative stress, ROS, nitrosative stress, genetically triggered thoracic aortic aneurysm, aortic dilatation, aortic dissection, Marfan syndrome, Bicuspid Aortic Valve, familial TAAD, Loeys Dietz syndrome, and Ehlers Danlos syndrome. Results: There is extensive evidence of oxidative stress and ROS imbalance in genetically triggered TAA. Sources of ROS imbalance are variable but include dysregulation of redox mediators leading to either insufficient ROS removal or increased ROS production. Therapeutic exploitation of redox mediators is being explored in other cardiovascular conditions, with potential application to TAA warranting further investigation. Conclusion: Oxidative stress occurs in genetically triggered TAA, but the precise contribution of ROS to pathogenesis remains incompletely understood. Further research is required to define causative pathological relationships in order to develop therapeutic options.

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Section: Sources Of Ros Imbalancementioning

confidence: 99%

Oxidative stress in genetically triggered thoracic aortic aneurysm: role in pathogenesis and therapeutic opportunities

et al. 2021

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“…A mouse model of MFS ( Fbn1 C1039G/+ mice) provides strong evidence of the involvement of MPO in the pathogenesis of TAA [ 121 ]. MPO knockout in this MFS mouse model resulted in decreased ROS production, associated with decreased VSMC apoptosis, decreased elastin fragmentation, and decreased MMP activation within the aortic wall, consistent with a central role for MPO in mediating these important pathological characteristics of MFS aneurysms.…”

Section: Mpo-associated Oxidative Stress and Links To Taa Pathogenmentioning

confidence: 99%

The Role of Inflammation and Myeloperoxidase-Related Oxidative Stress in the Pathogenesis of Genetically Triggered Thoracic Aortic Aneurysms

Malecki

Hambly

Jeremy

et al. 2020

IJMS

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Genetically triggered thoracic aortic aneurysms (TAAs) are usually considered to exhibit minimal levels of inflammation. However, emerging data demonstrate that specific features of an inflammatory response can be observed in TAA, and that the extent of the inflammatory response can be correlated with the severity, in both mouse models and in human studies. Myeloperoxidase (MPO) is a key mediator of the inflammatory response, via production of specific oxidative species, e.g., the hypohalous acids. Specific tissue modifications, mediated by hypohalous acids, have been documented in multiple cardiovascular pathologies, including atherosclerosis associated with coronary artery disease, abdominal aortic, and cerebral aneurysms. Similarly, data are now emerging that show the capacity of MPO-derived oxidative species to regulate mechanisms important in TAA pathogenesis, including alterations in extracellular matrix homeostasis, activation of matrix metalloproteinases, induction of endothelial dysfunction and vascular smooth muscle cell phenotypic switching, and activation of ERK1/2 signaling. The weight of evidence supports a role for inflammation in exacerbating the severity of TAA progression, expanding our understanding of the pathogenesis of TAA, identifying potential biomarkers for early detection of TAA, monitoring severity and progression, and for defining potential novel therapeutic targets.

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Aortic Wall Inflammation in the Pathogenesis, Diagnosis and Treatment of Aortic Aneurysms

et al. 2022

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P4551Myeloperoxidase activity aggravates aortic wall remodeling and participates in aneurysm development in Marfan Syndrome

Cited by 4 publications

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Oxidative stress in genetically triggered thoracic aortic aneurysm: role in pathogenesis and therapeutic opportunities

Oxidative stress in genetically triggered thoracic aortic aneurysm: role in pathogenesis and therapeutic opportunities

The Role of Inflammation and Myeloperoxidase-Related Oxidative Stress in the Pathogenesis of Genetically Triggered Thoracic Aortic Aneurysms

Aortic Wall Inflammation in the Pathogenesis, Diagnosis and Treatment of Aortic Aneurysms

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