Intracellular retention of mutant lysyl oxidase leads to aortic dilation in response to increased hemodynamic stress.

ABSTRACT: Heterozygous missense mutations in lysyl oxidase (LOX) are associated with thoracic aortic aneurysms and dissections. To assess how LOX mutations modify protein function and lead to aortic disease, we studied the factors that influence the onset and progression of vascular aneurysms in mice bearing a Lox mutation (p.M292R) linked to aortic dilation in humans. We show that mice heterozygous for the M292R mutation did not develop aneurysmal disease unless challenged with increased hemodynamic stress. Vessel dilation was confined to the ascending aorta although both the ascending and descending aortae showed changes in vessel wall structure, smooth muscle cell number and inflammatory cell recruitment that differed between wild-type and mutant animals. Studies with isolated cells found that M2

SUBMITTER: Lee VS 

PROVIDER: S-EPMC6693828 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature