Department of Biomedical Engineering, Yale University , New Haven, CT, USA.
LMGC, Univ. Montpellier, CNRS , Montpellier, France.
J R Soc Interface. 2024 Aug;21(217):20240110. doi: 10.1098/rsif.2024.0110. Epub 2024 Aug 28.
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.
肾素-血管紧张素系统在调节血压中起着关键作用,这促使人们对相关的高血压动脉重塑小鼠模型进行了许多研究。这些研究通常侧重于组织学和细胞生物学变化,而不是壁力学。本研究探讨了慢性血管紧张素 II 输注在野生型(WT)和 1 型血管紧张素 II(AngII)受体缺失()小鼠中的组织水平的影响。在这些小鼠接受血管紧张素 II 输注 14 和 28 天后,对其胸主动脉和腹主动脉进行了双轴生物力学和免疫组织化学变化的定量和比较。初步结果表明,这些变化在很大程度上与性别无关。雄性小鼠的胸主动脉和腹主动脉以及不同基因型之间的血管壁增厚和僵硬变化差异显著。尽管 WT 和 小鼠的生物力学变化多样,但血管紧张素 II 输注导致 WT 而非 小鼠的降胸主动脉出现独特的壁增厚和炎症。我们的研究强调了探索沿主动脉的受体依赖性血管紧张素 II 信号转导的差异作用及其对参与区域组织力学重塑的不同细胞类型的影响的重要性。阻断 AT1b 受体主要影响炎症细胞反应和平滑肌收缩性,提示潜在的治疗靶点。