Journal article
Extracellular BRICK1 drives heart repair after myocardial infarction in mice
Science translational medicine, Vol.18(831), p.eadx2876
01/07/2026
DOI: 10.1126/scitranslmed.adx2876
PMID: 41499524
Abstract
Tissue repair after myocardial infarction entails a vigorous angiogenic response that mitigates scarring and worsening of heart function. Angiogenesis in the infarct wound is guided by incompletely defined myeloid cell-endothelial cell interactions. Here, we identify the 75-amino acid microprotein BRICK1 (BRK1) as an indispensable driver of postinfarction angiogenesis in a mouse model of reperfused myocardial infarction. We show that BRK1 is preferentially expressed by myeloid cells and translocates to the extracellular space after myocardial infarction in mice and humans. As a subunit of the intracellular actin-regulatory WAVE complex, BRK1 was not previously known to function outside the cell. We find that BRK1 is not actively secreted but released during myeloid cell death. Cre-loxP-driven myeloid cell-selective genetic deletion of Brk1 or antibody-mediated neutralization of extracellular BRK1 impaired microvessel formation in the infarct border zone and resulted in severe postinfarction heart failure in mice. Conversely, treatment with recombinant BRK1 preserved heart function in infarcted mice. Mechanistically, BRK1 induced an angiogenic phenotype in human cardiac endothelial cells by signaling via the small GTPase Ras-related protein Rap-1 and mitogen-activated protein kinases 1 and 3 to promote retinoblastoma protein hyperphosphorylation and E2F transcription factor activation. BRK1 thus emerges as an angiogenic factor linking myeloid cell death to ischemic tissue repair, potentially enabling a protein-based therapy for myocardial infarction.
Details
- Title: Subtitle
- Extracellular BRICK1 drives heart repair after myocardial infarction in mice
- Creators
- Felix Polten - Medizinische Hochschule HannoverMircea-Andrei Sandu - Medizinische Hochschule HannoverJan Faix - Medizinische Hochschule HannoverJan Hegermann - Medizinische Hochschule HannoverNils Kriedemann - Medizinische Hochschule HannoverRobert Zweigerdt - Medizinische Hochschule HannoverThomas Thum - Medizinische Hochschule HannoverJohann Bauersachs - Medizinische Hochschule HannoverHans W. Niessen - Amsterdam University Medical CentersAndrew L. Koenig - Washington University in St. LouisKory J. Lavine - Washington University in St. LouisAndreas Pich - Medizinische Hochschule HannoverYong Wang - Medizinische Hochschule HannoverMarc R. Reboll - Medizinische Hochschule HannoverMortimer Korf-Klingebiel - Medizinische Hochschule HannoverKai C. Wollert - Medizinische Hochschule Hannover
- Resource Type
- Journal article
- Publication Details
- Science translational medicine, Vol.18(831), p.eadx2876
- DOI
- 10.1126/scitranslmed.adx2876
- PMID
- 41499524
- NLM abbreviation
- Sci Transl Med
- ISSN
- 1946-6234
- eISSN
- 1946-6242
- Publisher
- Amer Assoc Advancement Science
- Number of pages
- 13
- Grant note
- GSSP 57243780 / German Academic Exchange Service; Deutscher Akademischer Austausch Dienst (DAAD) KFO311 WO 552/11-1; KFO311 WO 552/11-2; KFO311 ZW 64/7-1; FA 330/12-3 / German Research Foundation; German Research Foundation (DFG)
- Language
- English
- Date published
- 01/07/2026
- Academic Unit
- Stead Family Department of Pediatrics
- Record Identifier
- 9985161354502771
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