Early clinical outcomes and molecular smooth muscle cell phenotyping using a prophylactic aortic arch replacement strategy in Loeys-Dietz syndrome

Pedroza, Albert J; Cheng, Paul; Dalal, Alex R.; Bäumler, Kathrin; Kino, Aya; Tognozzi, Emily; Shad, Rohan; Yokoyama, Nobu; Nakamura, Ken; Mitchel, Olivia; Hiesinger, William; MacFarlane, Elena Gallo; Fleischmann, Dominik; Woo, Y. Joseph; Quertermous, Thomas; Fischbein, Michael P.

doi:10.1016/j.jtcvs.2023.07.023

Cited by 1 publication

(2 citation statements)

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“…3D and Supplemental Fig. 4) 59 . Subpopulations of VSMCs expressing cluster-defining transcripts analogous to those found in VSMC1 and VSMC2 in mouse aortas could be identified in the human dataset ( Fig.…”

Section: Resultsmentioning

confidence: 98%

“…For re-analysis of the ascending aorta and aortic root samples from a recently published scRNAseq dataset of the donor and LDS patient aortas 59 we used the following criteria: > 1000 transcripts detected per cell but< 6000, > 1500 total molecules detected per cell < 30000, and < 20% mitochondrial transcripts per cell. This reduces this dataset from 58,947 aortic cells to 43,349 for further analysis.…”

Section: Methodsmentioning

confidence: 99%

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Intrinsic Gata4 expression sensitizes the aortic root to dilation in a Loeys-Dietz syndrome mouse model

Bramel,

Camejo,

Creamer

et al. 2024

Preprint

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Loeys-Dietz syndrome (LDS) is an aneurysm disorder caused by mutations that decrease transforming growth factor-β (TGF-β) signaling. Although aneurysms develop throughout the arterial tree, the aortic root is a site of heightened risk. To identify molecular determinants of this vulnerability, we investigated the heterogeneity of vascular smooth muscle cells (VSMCs) in the aorta of Tgfbr1M318R/+ LDS mice by single cell and spatial transcriptomics. 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 differentiated, proinflammatory profile. A similar population was also identified among aortic VSMCs in a human scRNAseq dataset. Postnatal VSMC-specific Gata4 deletion reduced aortic root dilation in LDS mice, suggesting that this factor sensitizes the aortic root to the effects of impaired TGF-β signaling.

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Section: Resultsmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%