Spatiotemporal signaling underlies progressive vascular rarefaction in myocardial infarction

Lin Wei Tung, Elena Groppa, Hesham Soliman, Bruce Lin, Chihkai Chang, Chun Wai Cheung, Morten Ritso, David Guo, Lucas Rempel, Sarthak Sinha, Christine Eisner, Julyanne Brassard, Kelly McNagny, Jeff Biernaskie and Fabio Rossi ()
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Lin Wei Tung: University of British Columbia
Elena Groppa: University of British Columbia
Hesham Soliman: University of British Columbia
Bruce Lin: University of British Columbia
Chihkai Chang: University of British Columbia
Chun Wai Cheung: University of British Columbia
Morten Ritso: University of British Columbia
David Guo: University of British Columbia
Lucas Rempel: University of British Columbia
Sarthak Sinha: University of Calgary
Christine Eisner: University of British Columbia
Julyanne Brassard: University of British Columbia
Kelly McNagny: University of British Columbia
Jeff Biernaskie: University of Calgary
Fabio Rossi: University of British Columbia

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract 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.

Date: 2023
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-44227-6

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DOI: 10.1038/s41467-023-44227-6

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