Abstract 131: Gata4 Ablation In Smooth Muscle Cells Reduces Aortic Root Dilation In A Murine Model Of Loeys-Dietz Syndrome

• DOI: 10.1161/atvb.41.suppl_1.131
• Publication Date: 2022-05-02T13:59:41Z
• Authors: Emily E Bramel; Muzna Saqib; Tyler J Creamer; Elena Gallo MacFa...
• Keywords: Periostin; GATA4

Loeys-Dietz syndrome (LDS) is a connective tissue disorder characterized by predisposition to aneurysm. Although dilation can develop in all segments of the arterial tree, aortic root especially prone disease. This region primarily composed vascular smooth muscle cells (VSMCs) derived from secondary heart field (SHF) progenitors, while VSMCs cardiac neural crest (CNC) predominate more distal ascending aorta. intrinsic differences have been found between these two types VSMCs, it remains unclear how may contribute localized risk. To identify transcripts associated with vulnerability LDS, we performed single cell transcriptomic analysis on proximal aortas 16-week-old control and Tgfbr1 M318R/+ LDS mice, which carry kinase-inactivating mutation TGF-β Receptor 1. We identified four major VSMC clusters regardless genotype, being defined CNC-enriched SHF-enriched transcripts. The latter were expression Gata4 , codes for transcription factor required development SHF-derived structures, as well higher previously involved aneurysm pathogenesis such Thbs1 Tgfb1, Tgfb3. In situ RNA hybridization confirmed that -expressing enriched aorta, almost no suggesting this transcript most susceptible effects mutation. GATA4 protein levels also upregulated mice. test if excessive or activity contributed generated mice was specifically deleted tamoxifen administration at 6 weeks age. intervention significantly reduced growth 8 20 mechanisms remain under investigation, data suggest might sensitize specific subsets an mutation, rendering