Résumé
The healthy adult aorta exhibits a remarkable homeostatic ability to respond to sustained changes in hemodynamic loads under many circumstances, but this mechanical homeostasis can be compromised or lost in natural aging and diverse pathological processes. Herein, we investigate persistent non-homeostatic changes in the composition and mechanical properties of the thoracic aorta in adult wild-type mice following 14 days of angiotensin II-induced hypertension. We employ a multiscale computational model of arterial growth and remodeling driven by mechanosensitive and angiotensin II-related cell signaling pathways. We find that experimentally observed findings can only be recapitulated computationally if the collagen deposited during the transient period of hypertension has altered properties (deposition stretch, fiber angle, crosslinking) compared with the collagen produced in the original homeostatic state. Some of these changes are predicted to persist for at least six months after blood pressure is restored to normal levels, consistent with the experimental findings.