Inducing Hypertension in Myh11R247C/R247C Mice Triggers Aortic Dissections With Increased Focal Adhesion Kinase Signaling

Authors

Callie S Kwartler
Shanzhi Wang
Zhen Zhou
Pujun Guan
Yang Yu
Xue-Yan Duan
Theodore Zhang
Jiyuan Chen
Elaine C Davis
Dianna M Milewicz

Language

English

Publication Date

1-1-2025

Journal

Frontiers in Cardiovascular Medicine

DOI

10.3389/fcvm.2025.1492768

PMID

40027514

PMCID

PMC11868086

PubMedCentral® Posted Date

2-14-2025

PubMedCentral® Full Text Version

Post-print

Abstract

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 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.

Conclusion: Gene-environment interactions trigger aortic dissections in Myh11R247C/R247C mice.

Keywords

myosin heavy chain, focal adhesion, elastin-contractile unit, thoracic aortic dissection, vascular disease, aortic dissection, smooth muscle cell (SMC)

Published Open-Access

yes

Recommended Citation

Kwartler, Callie S; Wang, Shanzhi; Zhou, Zhen; et al., "Inducing Hypertension in Myh11R247C/R247C Mice Triggers Aortic Dissections With Increased Focal Adhesion Kinase Signaling" (2025). Faculty, Staff and Student Publications. 6037.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6037