Inducing hypertension in Myh11R247C/R247C mice triggers aortic dissections with increased focal adhesion kinase signaling

作者：Callie Kwartler, Shanzhi Wang, Zhen Zhou, Pujun Guan, Yang Yu, Xueyan Duan, Theodore Zhang, Jiyuan Chen, Elaine C. Davis, Dianna M. Milewicz · 发表于：Frontiers in Cardiovascular Medicine · 年份：2025 · DOI：10.3389/fcvm.2025.1492768 · 被引用次数：5 · 研究领域：Aortic Disease and Treatment Approaches、Aortic aneurysm repair treatments、Connective tissue disorders research

Objective We sought to determine if hypertension in combination with a “variant of uncertain significance” that disrupts protein function, MYH11 p.Arg247Cys, would induce aortic dissections in a mouse model. Approach and results Administration of L-NAME via drinking water and a high salt diet increased blood pressure in WT and Myh11 R247C/R247C mice and triggered type A dissections with cardiac tamponade in 20% of the Myh11 R247C/R247C mice. Myh11 R247C/R247C aortas have aberrant smooth muscle contractile unit-elastin connections by transmission electron microscopy, along with increased focal adhesion signaling at baseline, which further increases with hypertension. Conclusion Gene-environment interactions trigger aortic dissections in Myh11 R247C/R247C mice.