Intrinsic GATA4 expression sensitizes the aortic root to dilation in a Loeys-Dietz syndrome mouse model.

ABSTRACT: Loeys-Dietz syndrome (LDS) is a connective tissue disorder caused by mutations that decrease transforming growth factor-β signaling. LDS-causing mutations increase the risk of aneurysm throughout the arterial tree, yet the aortic root is a site of heightened susceptibility. Here we investigate the heterogeneity of vascular smooth muscle cells (VSMCs) in the aorta of Tgfbr1^M318R/+ LDS mice by single-cell transcriptomics to identify molecular determinants of this vulnerability. Reduced expression of components of the extracellular matrix-receptor apparatus and upregulation of stress and inflammatory pathways were observed in all LDS VSMCs. However, regardless of genotype, a subset of Gata4-expressing VSMCs predominantly located in the aortic root intrinsically displayed a less dif

SUBMITTER: Bramel EE 

PROVIDER: S-EPMC11634776 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature