Spatiotemporal signaling underlies progressive vascular rarefaction in myocardial infarction.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
21 Dec 2023
21 Dec 2023
Historique:
received:
04
08
2022
accepted:
05
12
2023
medline:
22
12
2023
pubmed:
22
12
2023
entrez:
21
12
2023
Statut:
epublish
Résumé
Therapeutic angiogenesis represents a promising avenue to revascularize the ischemic heart. Its limited success is partly due to our poor understanding of the cardiac stroma, specifically mural cells, and their response to ischemic injury. Here, we combine single-cell and positional transcriptomics to assess the behavior of mural cells within the healing heart. In response to myocardial infarction, mural cells adopt an altered state closely associated with the infarct and retain a distinct lineage from fibroblasts. This response is concurrent with vascular rarefaction and reduced vascular coverage by mural cells. Positional transcriptomics reveals that the infarcted heart is governed by regional-dependent and temporally regulated programs. While the remote zone acts as an important source of pro-angiogenic signals, the infarct zone is accentuated by chronic activation of anti-angiogenic, pro-fibrotic, and inflammatory cues. Together, our work unveils the spatiotemporal programs underlying cardiac repair and establishes an association between vascular deterioration and mural cell dysfunction.
Identifiants
pubmed: 38129410
doi: 10.1038/s41467-023-44227-6
pii: 10.1038/s41467-023-44227-6
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
8498Subventions
Organisme : Heart and Stroke Foundation of Canada (Heart and Stroke Foundation)
ID : G-19-0026541
Organisme : Faculty of Medicine, University of British Columbia
ID : The Four-Year Doctoral Fellowship
Informations de copyright
© 2023. The Author(s).
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