Spatiotemporal signaling underlies progressive vascular rarefaction in myocardial infarction.

Autor: Tung LW; School of Biomedical Engineering & Department of Medical Genetics, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada., Groppa E; School of Biomedical Engineering & Department of Medical Genetics, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.; Borea Therapeutics, Scuola Internazionale Superiore di Studi Avanzati, Via Bonomea, 265, 34136, Trieste, Italy., Soliman H; School of Biomedical Engineering & Department of Medical Genetics, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.; Aspect Biosystems, 1781 W 75th Ave, Vancouver, BC, V6P 6P2, Canada.; Faculty of Pharmaceutical Sciences, Minia University, Minia, Egypt., Lin B; School of Biomedical Engineering & Department of Medical Genetics, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada., Chang C; School of Biomedical Engineering & Department of Medical Genetics, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada., Cheung CW; School of Biomedical Engineering & Department of Medical Genetics, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada., Ritso M; School of Biomedical Engineering & Department of Medical Genetics, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada., Guo D; School of Biomedical Engineering & Department of Medical Genetics, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada., Rempel L; School of Biomedical Engineering & Department of Medical Genetics, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada., Sinha S; Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada.; Department of Surgery, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada., Eisner C; School of Biomedical Engineering & Department of Medical Genetics, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada., Brassard J; School of Biomedical Engineering & Department of Medical Genetics, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada., McNagny K; School of Biomedical Engineering & Department of Medical Genetics, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada., Biernaskie J; Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada.; Department of Surgery, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada., Rossi F; School of Biomedical Engineering & Department of Medical Genetics, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada. fabio@brc.ubc.ca.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Dec 21; Vol. 14 (1), pp. 8498. Date of Electronic Publication: 2023 Dec 21.
DOI: 10.1038/s41467-023-44227-6
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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