Hypertension induces significant aortic remodelling, often adaptive but sometimes not. To identify immuno-mechanical mechanisms responsible for differential remodelling, we studied thoracic aortas from 129S6/SvEvTac and C57BL/6 J mice before and after continuous 14-day angiotensin II infusion, which elevated blood pressure similarly in both strains. Histological and biomechanical assessments of excised vessels were similar at baseline, suggesting a common homeostatic set-point for mean wall stress. Histology further revealed near mechano-adaptive remodelling of the hypertensive 129S6/SvEvTac aortas, but a grossly maladaptive remodelling of C57BL/6 J aortas. Bulk RNA sequencing suggested that increased smooth muscle contractile processes promoted mechano-adaptation of 129S6/SvEvTac aortas while immune processes prevented adaptation of C57BL/6 J aortas. Functional studies confirmed an increased vasoconstrictive capacity of the former while immunohistochemistry demonstrated marked increases in inflammatory cells in the latter. We then used multiple computational biomechanical models to test the hypothesis that excessive adventitial wall stress correlates with inflammatory cell infiltration. These models consistently predicted that increased vasoconstriction against an increased pressure coupled with modest deposition of new matrix thickens the wall appropriately, restoring wall stress towards homeostatic consistent with adaptive remodelling. By contrast, insufficient vasoconstriction permits high wall stresses and exuberant inflammation-driven matrix deposition, especially in the adventitia, reflecting compromised homeostasis and gross maladaptation.

高血压引起显着的主动脉重塑，通常是适应性的，但有时不是。为了确定导致差异重塑的免疫机械机制，我们研究了 129S6/SvEvTac 和 C57BL/6 J 小鼠在连续 14 天血管紧张素 II 输注前后的胸主动脉，这两种品系的血压升高相似。切除血管的组织学和生物力学评估在基线时相似，表明平均壁应力有一个共同的稳态设定点。组织学进一步揭示了高血压 129S6/SvEvTac 主动脉的近机械适应性重塑，但 C57BL/6 J 主动脉的严重适应不良重塑。大量 RNA 测序表明，增加的平滑肌收缩过程促进了 129S6/SvEvTac 主动脉的机械适应，而免疫过程阻止了 C57BL/6 J 主动脉的适应。功能研究证实前者的血管收缩能力增加，而免疫组织化学表明后者的炎症细胞显着增加。然后，我们使用多个计算生物力学模型来检验过度外膜壁应力与炎症细胞浸润相关的假设。这些模型一致预测，针对压力增加而增加的血管收缩加上新基质的适度沉积会适当地增厚壁，使壁应力恢复到与适应性重塑一致的稳态。相比之下，