Understanding the pathogenesis of abdominal aortic aneurysms

Kuivaniemi, Helena; Ryer, Evan J.; Elmore, James R.; Tromp, Gerard

doi:10.1586/14779072.2015.1074861

Cited by 305 publications

(280 citation statements)

References 109 publications

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“…Based on these observations, we concluded that VPO1 modulates VSMC phenotypic switch through H 2 O 2 /VPO1/HOCl/ERK1/2 signaling pathway, which plays a key role in the formation of AAA. Oxidative stress has been described as an important signaling pathway in human AAA development and animal models of AAA 21, 22. The specific identity of reactive oxygen species that is responsible for the development of aortic dilation remains elusive 4, 23, 24.…”

Section: Discussionmentioning

confidence: 99%

VPO1 Modulates Vascular Smooth Muscle Cell Phenotypic Switch by Activating Extracellular Signal‐regulated Kinase 1/2 (ERK 1/2) in Abdominal Aortic Aneurysms

Peng

Zhang

Liu

et al. 2018

JAHA

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BackgroundHydrogen peroxide (H2O2) is a critical molecular signal in the development of abdominal aortic aneurysm (AAA) formation. Vascular peroxidase 1 (VPO1) catalyzes the production of hypochlorous acid (HOCl) from H2O2 and significantly enhances oxidative stress. The switch from a contractile phenotype to a synthetic one in vascular smooth muscle cells (VSMCs) is driven by reactive oxygen species and is recognized as an early and important event in AAA formation. This study aims to determine if VPO1 plays a critical role in the development of AAA by regulating VSMC phenotypic switch.Methods and Results VPO1 is upregulated in human and elastase‐induced mouse aneurysmal tissues compared with healthy control tissues. Additionally, KLF4, a nuclear transcriptional factor, is upregulated in aneurysmatic tissues along with a concomitant downregulation of differentiated smooth muscle cell markers and an increase of synthetic phenotypic markers, indicating VSMC phenotypic switch in these diseased tissues. In cultured VSMCs from rat abdominal aorta, H2O2 treatment significantly increases VPO1 expression and HOCl levels as well as VSMC phenotypic switch. In support of these findings, depletion of VPO1 significantly attenuates the effects of H2O2 and HOCl treatment. Furthermore, HOCl treatment promotes VSMC phenotypic switch and ERK1/2 phosphorylation. Pretreatment with U0126 (a specific inhibitor of ERK1/2) significantly attenuates HOCl‐induced VSMC phenotypic switch.ConclusionsOur results demonstrate that VPO1 modulates VSMC phenotypic switch through the H2O2/VPO1/HOCl/ERK1/2 signaling pathway and plays a key role in the development of AAA. Our findings also implicate VPO1 as a novel signaling node that mediates VSMC phenotypic switch and plays a key role in the development of AAA.Clinical Trial Registration URL: http://www.chictr.org.cn. Unique identifier: ChiCTR1800016922.

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Section: Discussionmentioning

confidence: 99%

VPO1 Modulates Vascular Smooth Muscle Cell Phenotypic Switch by Activating Extracellular Signal‐regulated Kinase 1/2 (ERK 1/2) in Abdominal Aortic Aneurysms

Peng

Zhang

Liu

et al. 2018

JAHA

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“…The natural course of an abdominal aortic aneurysm (AAA) is a steady increase of the diameter, and eventually, if left untreated, the aneurysm might rupture 1. In most cases of AAA, this pathophysiological process remains asymptomatic until rupture.…”

Section: Introductionmentioning

confidence: 99%

Systematic Review of Circulating, Biomechanical, and Genetic Markers for the Prediction of Abdominal Aortic Aneurysm Growth and Rupture

Groeneveld

Meekel

Rubinstein

et al. 2018

JAHA

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BackgroundThe natural course of abdominal aortic aneurysms (AAA) is growth and rupture if left untreated. Numerous markers have been investigated; however, none are broadly acknowledged. Our aim was to identify potential prognostic markers for AAA growth and rupture.Methods and ResultsPotential circulating, biomechanical, and genetic markers were studied. A comprehensive search was conducted in PubMed, Embase, and Cochrane Library in February 2017, following Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Study selection, data extraction, and methodological quality assessment were conducted by 2 independent researchers. Plausibility of markers was based on the amount of publications regarding the marker (more than 3), pooled sample size (more than 100), bias risk and statistical significance of the studies. Eighty‐two studies were included, which examined circulating (n=40), biomechanical (n=27), and genetic markers (n=7) and combinations of markers (n=8). Factors with an increased expansion risk included: AAA diameter (9 studies; n=1938; low bias risk), chlamydophila pneumonia (4 studies; n=311; medium bias risk), S‐elastin peptides (3 studies; n=205; medium bias risk), fluorodeoxyglucose uptake (3 studies; n=104; medium bias risk), and intraluminal thrombus size (5 studies; n=758; medium bias risk). Factors with an increased rupture risk rupture included: peak wall stress (9 studies; n=579; medium bias risk) and AAA diameter (8 studies; n=354; medium bias risk). No meta‐analysis was conducted because of clinical and methodological heterogeneity.ConclusionsWe identified 5 potential markers with a prognostic value for AAA growth and 2 for rupture. While interpreting these data, one must realize that conclusions are based on small sample sizes and clinical and methodological heterogeneity. Prospective and methodological consonant studies are strongly urged to further study these potential markers.

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“…La capa media de la aorta torácica cuenta con alrededor de 60 unidades divididas en regiones vasculares y avasculares, mientras que la abdominal es completamente avascular y cuenta con alrededor de 30 unidades. Debido a las diferencias estructurales en los aneurismas torácicos y aórticos, generalmente no se presentan de manera concomitante, con solo un 10-15% de probabilidad de que un individuo presente enfermedad aneurismática en ambas porciones de la aorta 21 . Sin embargo, cabe señalar que en este estudio encontramos patología concomitante aislada en nueve pacientes y aneurismas con extensión toracoabdominal en 22 individuos.…”

Section: Figura 5 Gráfico De Regresión Lineal De La Población Estudiunclassified

Valor predictivo del tamizaje con tomografía computarizada en la detección de aneurismas aórticos en la población mexicana mayor de 55 años

Hinojosa¹,

Anaya‐Ayala²,

Bermúdez-Serrato³

et al. 2019

GMM

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Understanding the pathogenesis of abdominal aortic aneurysms

Cited by 305 publications

References 109 publications

VPO1 Modulates Vascular Smooth Muscle Cell Phenotypic Switch by Activating Extracellular Signal‐regulated Kinase 1/2 (ERK 1/2) in Abdominal Aortic Aneurysms

VPO1 Modulates Vascular Smooth Muscle Cell Phenotypic Switch by Activating Extracellular Signal‐regulated Kinase 1/2 (ERK 1/2) in Abdominal Aortic Aneurysms

Systematic Review of Circulating, Biomechanical, and Genetic Markers for the Prediction of Abdominal Aortic Aneurysm Growth and Rupture

Valor predictivo del tamizaje con tomografía computarizada en la detección de aneurismas aórticos en la población mexicana mayor de 55 años

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