Targeting cardiomyocyte ADAM10 ectodomain shedding promotes survival early after myocardial infarction

Research output: Contribution to journalResearch articleContributedpeer-review



After myocardial infarction the innate immune response is pivotal in clearing of tissue debris as well as scar formation, but exaggerated cytokine and chemokine secretion with subsequent leukocyte infiltration also leads to further tissue damage. Here, we address the value of targeting a previously unknown a disintegrin and metalloprotease 10 (ADAM10)/CX3CL1 axis in the regulation of neutrophil recruitment early after MI. We show that myocardial ADAM10 is distinctly upregulated in myocardial biopsies from patients with ischemia-driven cardiomyopathy. Intriguingly, upon MI in mice, pharmacological ADAM10 inhibition as well as genetic cardiomycyte-specific ADAM10 deletion improves survival with markedly enhanced heart function and reduced scar size. Mechanistically, abolished ADAM10-mediated CX3CL1 ectodomain shedding leads to diminished IL-1β-dependent inflammation, reduced neutrophil bone marrow egress as well as myocardial tissue infiltration. Thus, our data shows a conceptual insight into how acute MI induces chemotactic signaling via ectodomain shedding in cardiomyocytes.


Original languageEnglish
Article number7648
JournalNature communications
Issue number1
Publication statusPublished - Dec 2022

External IDs

Scopus 85143720104
PubMed 36496449
Mendeley 6828270a-a91b-34bb-aefc-65b4fbb8410e
unpaywall 10.1038/s41467-022-35331-0
ORCID /0000-0001-6466-2589/work/142238097
ORCID /0009-0008-1895-4538/work/142248969
ORCID /0000-0003-2514-9429/work/148606774


DFG Classification of Subject Areas according to Review Boards

Subject groups, research areas, subject areas according to Destatis


  • Animals, Mice, ADAM10 Protein/genetics, Amyloid Precursor Protein Secretases/genetics, Leukocytes, Membrane Proteins/genetics, Myocardial Infarction/genetics, Humans