DataVXAdvanced SciencePaper
journal article·2023-02Open access

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

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

Advanced Science· Volume 10· Issue 5
Publisher pageOpen full text
Source abstract

Abstract

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.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Cardiac Fibrosis and Remodeling · Signaling Pathways in Disease · Immune cells in cancer

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Cardiovascular Research Institute Maastricht University Medical Center (CARIM) Maastricht University Maastricht The Netherlands

Department of Pathology Maastricht University Maastricht The Netherlands

Department of Physiology Maastricht University Maastricht The Netherlands

Institut für Humangenetik Westfälische Wilhelms‐Universität Münster Münster Germany

Department of Biochemistry Maastricht University Maastricht The Netherlands

Department of Internal Medicine Maastricht University Maastricht The Netherlands

Department of Cardiology Oslo University Hospital Rikshospitalet Oslo Norway

K. G. Jebsen Cardiac Research Centre and Centre for Heart Failure Research University of Oslo Oslo Norway

Department of Cardiology Oslo University Hospital Ullevål University of Oslo Oslo Norway

Research Institute of Internal Medicine Oslo University Hospital Rikshospitalet University of Oslo Oslo Norway

Department of Neurology Oslo University Hospital Rikshospitalet University of Oslo Oslo Norway

Section of Clinical Immunology and Infectious Diseases Oslo University Hospital Rikshospitalet University of Oslo Oslo Norway

Department of Data Science and Knowledge Engineering (DKE) Maastricht University Maastricht the Netherlands

Institute for Molecular Cardiovascular Research (IMCAR) Universitätsklinikum Aachen Aachen Germany

Funding

Hartstichting · China Scholarship Council · Stichting voor de Technische Wetenschappen

References (39)

Show source-provided references
1. 10.1016/j.cca.2011.02.03010.1016/j.cca.2011.02.030 ↗
2. 10.1038/s41598-019-45473-910.1038/s41598-019-45473-9 ↗
3. 10.1038/nature1126010.1038/nature11260 ↗
4. 10.1016/j.atherosclerosis.2013.04.00410.1016/j.atherosclerosis.2013.04.004 ↗
5. 10.1038/s41590-018-0272-210.1038/s41590-018-0272-2 ↗
6. 10.1093/cvr/cvz33610.1093/cvr/cvz336 ↗
7. 10.1093/cvr/cvy28610.1093/cvr/cvy286 ↗
8. 10.1016/j.immuni.2014.01.00610.1016/j.immuni.2014.01.006 ↗
9. 10.3389/fimmu.2019.0189310.3389/fimmu.2019.01893 ↗
10. 10.1161/JAHA.113.00067910.1161/JAHA.113.000679 ↗
11. 10.3390/ijms2020508610.3390/ijms20205086 ↗
12. 10.1186/s13073-015-0149-z10.1186/s13073-015-0149-z ↗
13. 10.1038/s41586-022-05060-x10.1038/s41586-022-05060-x ↗
14. 10.1016/j.yjmcc.2018.11.01210.1016/j.yjmcc.2018.11.012 ↗
15. 10.1016/j.immuni.2018.09.00510.1016/j.immuni.2018.09.005 ↗
16. 10.1016/j.cell.2017.10.04910.1016/j.cell.2017.10.049 ↗
17. 10.1210/en.2005-045110.1210/en.2005-0451 ↗
18. 10.1136/hrt.2003.02809210.1136/hrt.2003.028092 ↗
19. 10.1161/CIRCULATIONAHA.108.78185610.1161/CIRCULATIONAHA.108.781856 ↗
20. 10.3892/etm.2013.109510.3892/etm.2013.1095 ↗
21. 10.1016/j.ijcard.2008.04.05910.1016/j.ijcard.2008.04.059 ↗
22. 10.1007/s00395-018-0686-x10.1007/s00395-018-0686-x ↗
23. 10.1161/CIRCULATIONAHA.116.02180310.1161/CIRCULATIONAHA.116.021803 ↗
24. 10.1016/j.coph.2018.07.00210.1016/j.coph.2018.07.002 ↗
25. 10.1016/j.jacc.2021.02.04910.1016/j.jacc.2021.02.049 ↗
26. 10.3389/fcvm.2022.103129310.3389/fcvm.2022.1031293 ↗
27. 10.1038/s41591-018-0059-x10.1038/s41591-018-0059-x ↗
28. 10.1161/CIRCIMAGING.115.00414810.1161/CIRCIMAGING.115.004148 ↗
29. 10.1038/s41591-019-0590-410.1038/s41591-019-0590-4 ↗
30. 10.1016/j.immuni.2019.10.01010.1016/j.immuni.2019.10.010 ↗
31. Wu J. M. F. · J. Am. Heart Assoc. · 2018 · 7 · e00921610.1161/JAHA.118.009216 ↗
32. 10.1186/gb-2006-7-10-r10010.1186/gb-2006-7-10-r100 ↗
33. 10.1109/TPAMI.2005.15910.1109/TPAMI.2005.159 ↗
34. 10.1126/science.120543810.1126/science.1205438 ↗
35. Lundberg S. M. · Adv. Neural Inf. Process. Syst. · 2017 · 30
36. 10.1186/1471-2105-7-S1-S710.1186/1471-2105-7-S1-S7 ↗
37. 10.1016/j.cell.2018.01.02910.1016/j.cell.2018.01.029 ↗
38. 10.1186/1471-2105-14-710.1186/1471-2105-14-7 ↗
39. 10.1126/science.113293910.1126/science.1132939 ↗