Mapping the cardiac vascular niche in heart failure

Fabian Peisker, Maurice Halder, James Nagai, Susanne Ziegler, Nadine Kaesler, Konrad Hoeft, Ronghui Li, Eric M.J. Bindels, Christoph Kuppe, Julia Moellmann, Michael Lehrke, Christian Stoppe, Michael T. Schaub, Rebekka K. Schneider, Ivan Costa, Rafael Kramann*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

45 Citations (Scopus)
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Abstract

The cardiac vascular and perivascular niche are of major importance in homeostasis and during disease, but we lack a complete understanding of its cellular heterogeneity and alteration in response to injury as a major driver of heart failure. Using combined genetic fate tracing with confocal imaging and single-cell RNA sequencing of this niche in homeostasis and during heart failure, we unravel cell type specific transcriptomic changes in fibroblast, endothelial, pericyte and vascular smooth muscle cell subtypes. We characterize a specific fibroblast subpopulation that exists during homeostasis, acquires Thbs4 expression and expands after injury driving cardiac fibrosis, and identify the transcription factor TEAD1 as a regulator of fibroblast activation. Endothelial cells display a proliferative response after injury, which is not sustained in later remodeling, together with transcriptional changes related to hypoxia, angiogenesis, and migration. Collectively, our data provides an extensive resource of transcriptomic changes in the vascular niche in hypertrophic cardiac remodeling.

Original languageEnglish
Article number3027
JournalNature Communications
Volume13
Issue number1
Early online date31 May 2022
DOIs
Publication statusPublished - Dec 2022

Bibliographical note

Funding Information:
This work was supported by the National Natural Science Foundation of China (31671018, 81973255), Natural Science Foundation of Jiangsu Province-Outstanding Young Scientist Fund (BK20200031), Key Science Foundation of Jiangyin Health Commission (K202101).

Publisher Copyright:
© 2022, The Author(s).

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