Cristina Cavinato, Bart Spronck, Alexander W Caulk, Sae-Il Murtada, Jay D Humphrey
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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 <i>Agtr1b</i> <sup>-/-</sup> mice, AngII infusion caused distinctive wall thickening and inflammation in the descending thoracic aorta of WT, but not <i>Agtr1b</i> <sup>-/-</sup>, 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.</p>","PeriodicalId":17488,"journal":{"name":"Journal of The Royal Society Interface","volume":"21 217","pages":"20240110"},"PeriodicalIF":3.7000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11350382/pdf/","citationCount":"0","resultStr":"{\"title\":\"AT1b receptors contribute to regional disparities in angiotensin II mediated aortic remodelling in mice.\",\"authors\":\"Cristina Cavinato, Bart Spronck, Alexander W Caulk, Sae-Il Murtada, Jay D Humphrey\",\"doi\":\"10.1098/rsif.2024.0110\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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 (<i>Agtr1b</i> <sup>-/-</sup>) 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 <i>Agtr1b</i> <sup>-/-</sup> mice, AngII infusion caused distinctive wall thickening and inflammation in the descending thoracic aorta of WT, but not <i>Agtr1b</i> <sup>-/-</sup>, 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.</p>\",\"PeriodicalId\":17488,\"journal\":{\"name\":\"Journal of The Royal Society Interface\",\"volume\":\"21 217\",\"pages\":\"20240110\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2024-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11350382/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of The Royal Society Interface\",\"FirstCategoryId\":\"103\",\"ListUrlMain\":\"https://doi.org/10.1098/rsif.2024.0110\",\"RegionNum\":2,\"RegionCategory\":\"综合性期刊\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/8/28 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"MULTIDISCIPLINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of The Royal Society Interface","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1098/rsif.2024.0110","RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/28 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
引用次数: 0
摘要
肾素-血管紧张素系统在调节血压方面起着关键作用,这促使人们对高血压动脉重塑的相关小鼠模型进行了大量研究。这些研究通常侧重于组织学和细胞生物学变化,而不是血管壁力学。本研究探讨了在野生型(WT)和 1b 型血管紧张素 II(AngII)受体无效(Agtr1b -/-)小鼠中长期输注血管紧张素 II 在组织层面的影响。对输注血管紧张素 II 14 天和 28 天后这些小鼠胸主动脉和腹主动脉的双轴生物力学和免疫组织学变化进行了量化和比较。初步结果显示,这些变化在很大程度上与性别无关。雄性小鼠主动脉壁的相关增厚和僵化在胸部和腹部区域以及基因型之间存在显著差异。尽管 WT 小鼠和 Agtr1b -/- 小鼠都发生了多种生物力学变化,但输注 AngII 会导致 WT 小鼠降主动脉壁明显增厚和炎症,而 Agtr1b -/- 小鼠则不会。我们的研究强调了探索受体依赖性血管紧张素 II 信号在主动脉上的不同作用及其对参与区域组织机械重塑的不同细胞类型的影响的重要性。干扰 AT1b 受体主要会影响炎症细胞反应和平滑肌收缩力,这提示了潜在的治疗靶点。
AT1b receptors contribute to regional disparities in angiotensin II mediated aortic remodelling in mice.
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 (Agtr1b-/-) 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 Agtr1b-/- mice, AngII infusion caused distinctive wall thickening and inflammation in the descending thoracic aorta of WT, but not Agtr1b-/-, 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.
期刊介绍:
J. R. Soc. Interface welcomes articles of high quality research at the interface of the physical and life sciences. It provides a high-quality forum to publish rapidly and interact across this boundary in two main ways: J. R. Soc. Interface publishes research applying chemistry, engineering, materials science, mathematics and physics to the biological and medical sciences; it also highlights discoveries in the life sciences of relevance to the physical sciences. Both sides of the interface are considered equally and it is one of the only journals to cover this exciting new territory. J. R. Soc. Interface welcomes contributions on a diverse range of topics, including but not limited to; biocomplexity, bioengineering, bioinformatics, biomaterials, biomechanics, bionanoscience, biophysics, chemical biology, computer science (as applied to the life sciences), medical physics, synthetic biology, systems biology, theoretical biology and tissue engineering.