Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0162871 (
abdominal aortic aneurysm
)
8,664
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Background Hydrogen peroxide (H
2
O
2
) 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 H
2
O
2
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, H
2
O
2
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 H
2
O
2
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 H
2
O
2
/
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.
...
PMID:VPO1 Modulates Vascular Smooth Muscle Cell Phenotypic Switch by Activating Extracellular Signal-regulated Kinase 1/2 (ERK 1/2) in Abdominal Aortic Aneurysms. 3037 Nov 71
