English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background  Activation of the renin-angiotensin-aldosterone system (RAAS) plays a critical role in the development of hypertension. Published evidence on a putative “memory effect” of AngII on the vascular components is however scarce.    Aim  To evaluate the long-term effects of transient exposure to AngII on the mouse heart and the arterial tissue.    Methods  Blood pressure, cardiovascular tissue damage and remodeling, and systemic oxidative stress were evaluated in C57/B6/J mice at the end of a 2-week AngII infusion ( AngII ); 2 and 3 weeks after the interruption of a 2-week AngII treatment ( AngII + 2W  and  AngII  + 3W ; so-called “memory” conditions) and control littermate ( CTRL ). RNAseq profiling of aortic tissues was used to identify potential key regulated genes accounting for legacy effects on the vascular phenotype. RNAseq results were validated by RT-qPCR and immunohistochemistry in a reproduction cohort of mice. Key findings were reproduced in a homotypic cell culture model.    Results  The 2 weeks AngII infusion induced cardiac hypertrophy and aortic damage that persisted beyond AngII interruption and despite blood pressure normalization, with a sustained vascular expression of ICAM1, infiltration by CD45+ cells, and cell proliferation associated with systemic oxidative stress. RNAseq profiling in aortic tissue identified robust  Acta2  downregulation at transcript and protein levels (α-smooth muscle actin) that was maintained beyond interruption of AngII treatment. Among regulators of  Acta2  expression, the transcription factor Myocardin ( Myocd ), exhibited a similar expression pattern. The sustained downregulation of  Acta2  and  Myocd  was associated with an increase in H3K27me3 in nuclei of aortic sections from mice in the “memory” conditions. A sustained downregulation of  ACTA2  and  MYOCD  was reproduced in the cultured human aortic vascular smooth muscle cells upon transient exposure to Ang II.    Conclusion  A transient exposure to Ang II produces prolonged vascular remodeling with robust  ACTA2  downregulation, associated with epigenetic imprinting supporting a “memory” effect despite stimulus withdrawal.

Sustained Downregulation of Vascular Smooth Muscle Acta2 After Transient Angiotensin II Infusion: A New Model of “Vascular Memory”