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MRTF-A promotes angiotensin II-induced inflammatory response and aortic dissection in mice

ABSTRACT: Aortic dissection (AD) is a major cause of acute aortic syndrome with high mortality due to the destruction of aortic walls. Although recent studies indicate the critical role of inflammation in the disease mechanism of AD, it is unclear how inflammatory response is initiated. Here, we demonstrate that myocardin-related transcription factor A (MRTF-A), a signal transducer of humoral and mechanical stress, plays an important role in pathogenesis of AD in a mouse model. A mouse model of AD was created by continuous infusion of angiotensin II (AngII) that caused dilation of thoracic aorta in 1 day and AD in 4 days. Systemic deletion of Mrtfa gene resulted in a marked suppression of AD development. Transcriptome and gene annotation enrichment analyses revealed that AngII infusion for 1 day caused pro-inflammatory and pro-apoptotic responses before AD development, which were suppressed by Mrtfa deletion. AngII infusion for 1 day induced pro-inflammatory response, as demonstrated by expressions of Il6, Tnf , and Ccl2, and apoptosis of aortic wall cells, as detected by TUNEL staining, in an MRTF-A-dependent manner. Furthermore, pharmacological inhibition of MRTF-A by CCG-203971 during AngII infusion prevented AD development, indicating that acute suppression of MRTF-A is effective in preventing the aortic wall destruction. These results indicate that MRTF-A transduces the stress of AngII challenge to the pro-inflammatory and pro-apoptotic responses, ultimately leading to AD development. Intervening this pathway may represent a potential therapeutic strategy.

ORGANISM(S): Mus musculus

PROVIDER: GSE138484 | GEO | 2020/04/01

REPOSITORIES: GEO

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Expression data from MRTFA-B double knockout brain

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2010-06-16 | E-GEOD-22117 | biostudies-arrayexpress

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2020-04-01 | GSE147078 | GEO

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2016-11-07 | GSE81580 | GEO

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2018-05-08 | PXD009410 | Pride

Mus musculus

Project description:Control vs. AngII Infusion

| PRJNA85409 | ENA

Control vs. AngII Infusion

Project description:The genetic background of mice used in this study is mainly C57BL/6J with a small contribution from 129/Sv and DBA/2J strains. Male littermates were received continuous administration of AngII for 7 days at 0.9ug/hour. On day 7 of AngII infusion, the blood pressure of infused mice was (mmHg, mean ± SD) 156 ± 1, while the control littermates remained normotensive (106 ± 9). Keywords: other

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2023-12-18 | GSE240171 | GEO

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