AT1b receptors contribute to regional disparities in angiotensin II mediated aortic remodelling in mice

Cristina Cavinato*, Bart Spronck, Alexander W Caulk, Sae-Il Murtada, Jay D Humphrey*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The renin-angiotensin system plays a key role in regulating blood pressure, which has motivated many investigations of associated mouse models of hypertensive arterial remodelling. Such studies typically focus on histological and cell biological changes, not wall mechanics. This study explores tissue-level ramifications of chronic angiotensin II infusion in wild-type (WT) and type 1b angiotensin II (AngII) receptor null ( ) mice. Biaxial biomechanical and immunohistological changes were quantified and compared in the thoracic and abdominal aorta in these mice following 14 and 28 days of angiotensin II infusion. Preliminary results showed that changes were largely independent of sex. Associated thickening and stiffening of the aortic wall in male mice differed significantly between thoracic and abdominal regions and between genotypes. Notwithstanding multiple biomechanical changes in both WT and mice, AngII infusion caused distinctive wall thickening and inflammation in the descending thoracic aorta of WT, but not , mice. Our study underscores the importance of exploring differential roles of receptor-dependent angiotensin II signalling along the aorta and its influence on distinct cell types involved in regional histomechanical remodelling. Disrupting the AT1b receptor primarily affected inflammatory cell responses and smooth muscle contractility, suggesting potential therapeutic targets.
Original languageEnglish
Article number20240110
Number of pages12
JournalJournal of the Royal Society Interface
Volume21
Issue number217
DOIs
Publication statusPublished - 28 Aug 2024

Keywords

  • aorta
  • hypertension
  • inflammation
  • remodelling
  • sex
  • stiffness
  • Animals
  • Angiotensin II/pharmacology metabolism
  • Mice
  • Male
  • Receptor, Angiotensin, Type 1/metabolism genetics
  • Vascular Remodeling
  • Mice, Knockout
  • Female
  • Aorta, Thoracic/metabolism pathology

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