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• W2892017498 abstract "Background Hydrogen peroxide (H2O2) is a critical molecular signal in the development of abdominal aortic aneurysm ( AAA ) formation. Vascular peroxidase 1 ( VPO 1) catalyzes the production of hypochlorous acid ( HOC l) from H2O2 and significantly enhances oxidative stress. The switch from a contractile phenotype to a synthetic one in vascular smooth muscle cells ( VSMC s) is driven by reactive oxygen species and is recognized as an early and important event in AAA formation. This study aims to determine if VPO 1 plays a critical role in the development of AAA by regulating VSMC phenotypic switch. Methods and Results VPO 1 is upregulated in human and elastase-induced mouse aneurysmal tissues compared with healthy control tissues. Additionally, KLF 4, 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 VSMC s from rat abdominal aorta, H2O2 treatment significantly increases VPO 1 expression and HOC l levels as well as VSMC phenotypic switch. In support of these findings, depletion of VPO 1 significantly attenuates the effects of H2O2 and HOC l treatment. Furthermore, HOC l treatment promotes VSMC phenotypic switch and ERK 1/2 phosphorylation. Pretreatment with U0126 (a specific inhibitor of ERK 1/2) significantly attenuates HOC l-induced VSMC phenotypic switch. Conclusions Our results demonstrate that VPO 1 modulates VSMC phenotypic switch through the H2O2/ VPO 1/ HOC l/ ERK 1/2 signaling pathway and plays a key role in the development of AAA . Our findings also implicate VPO 1 as a novel signaling node that mediates VSMC phenotypic switch and plays a key role in the development of AAA . Clinical Trial Registration URL : www.chictr.org.cn . Unique identifier: Chi CTR 1800016922." @default.
• W2892017498 created "2018-09-27" @default.
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• W2892017498 date "2018-09-04" @default.
• W2892017498 modified "2023-10-14" @default.
• W2892017498 title "VPO1 Modulates Vascular Smooth Muscle Cell Phenotypic Switch by Activating Extracellular Signal‐regulated Kinase 1/2 (ERK 1/2) in Abdominal Aortic Aneurysms" @default.
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• W2892017498 doi "https://doi.org/10.1161/jaha.118.010069" @default.
• W2892017498 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6201418" @default.
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