Frontiers in Cardiovascular Medicine (Feb 2025)
Inducing hypertension in Myh11R247C/R247C mice triggers aortic dissections with increased focal adhesion kinase signaling
Abstract
ObjectiveWe 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 resultsAdministration of L-NAME via drinking water and a high salt diet increased blood pressure in WT and Myh11R247C/R247C mice and triggered type A dissections with cardiac tamponade in 20% of the Myh11R247C/R247C mice. Myh11R247C/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.ConclusionGene-environment interactions trigger aortic dissections in Myh11R247C/R247C mice.
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