Blood Milieu in Acute Myocardial Infarction Reprograms Human Macrophages for Trauma Repair

Abstract: Acute myocardial infarction (AMI) is accompanied by a systemic trauma response that impacts the whole body, including blood. This study addresses whether macrophages, key players in trauma repair, sense and respond to these changes. For this, healthy human monocyte‐derived macrophages are exposed to 20% human AMI (n = 50) or control (n = 20) serum and analyzed by transcriptional and multiparameter functional screening followed by network‐guided data interpretation and drug repurposing. Results are validated in an independent cohort at functional level (n = 47 AMI, n = 25 control) and in a public dataset. AMI serum exposure results in an overt AMI signature, enriched in debris cleaning, mitosis, and immune pathways. Moreover, gene networks associated with AMI and with poor clinical prognosis in AMI are identified. Network‐guided drug screening on the latter unveils prostaglandin E2 (PGE2) signaling as target for clinical intervention in detrimental macrophage imprinting during AMI trauma healing. The results demonstrate pronounced context‐induced macrophage reprogramming by the AMI systemic environment, to a degree decisive for patient prognosis. This offers new opportunities for targeted intervention and optimized cardiovascular disease risk management.

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch

Erschienen in
Blood Milieu in Acute Myocardial Infarction Reprograms Human Macrophages for Trauma Repair ; day:16 ; month:12 ; year:2022 ; extent:14
Advanced science ; (16.12.2022) (gesamt 14)

Urheber
Fontaine, Margaux A. C.
Jin, Han
Gagliardi, Mick
Rousch, Mat
Wijnands, Erwin
Stoll, Monika
Li, Xiaofei
Schurgers, Leon
Reutelingsperger, Chris
Schalkwijk, Casper
van den Akker, Nynke M. S.
Molin, Daniel G.M.
Gullestad, Lars
Eritsland, Jan
Hoffman, Pavel
Skjelland, Mona
Andersen, Geir Ø.
Aukrust, Pål
Karel, Joël
Smirnov, Evgueni
Halvorsen, Bente
Temmerman, Lieve
Biessen, Erik A.L.

DOI
10.1002/advs.202203053
URN
urn:nbn:de:101:1-2022121714224194430269
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
15.08.2025, 07:39 MESZ

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Beteiligte

  • Fontaine, Margaux A. C.
  • Jin, Han
  • Gagliardi, Mick
  • Rousch, Mat
  • Wijnands, Erwin
  • Stoll, Monika
  • Li, Xiaofei
  • Schurgers, Leon
  • Reutelingsperger, Chris
  • Schalkwijk, Casper
  • van den Akker, Nynke M. S.
  • Molin, Daniel G.M.
  • Gullestad, Lars
  • Eritsland, Jan
  • Hoffman, Pavel
  • Skjelland, Mona
  • Andersen, Geir Ø.
  • Aukrust, Pål
  • Karel, Joël
  • Smirnov, Evgueni
  • Halvorsen, Bente
  • Temmerman, Lieve
  • Biessen, Erik A.L.

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