An Myh11 single lysine deletion causes aortic dissection by reducing aortic structural integrity and contractility.

ABSTRACT: Pathogenic variants in myosin heavy chain (Myh11) cause familial thoracic aortic aneurysms and dissections (FTAAD). However, the underlying pathological mechanisms remain unclear because of a lack of animal models. In this study, we established a mouse model with Myh11 K1256del, the pathogenic variant we found previously in two FTAAD families. The Myh11^∆K/∆K aorta showed increased wall thickness and ultrastructural abnormalities, including weakened cell adhesion. Notably, the Myh11^∆K/+ mice developed aortic dissections and intramural haematomas when stimulated with angiotensin II. Mechanistically, integrin subunit alpha2 (Itga2) was downregulated in the Myh11^∆K/∆K aortas, and the smooth muscle cell lineage cells that differentiated from Myh11^∆K/∆K

SUBMITTER: Negishi K 

PROVIDER: S-EPMC9133116 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature