IGF1 Treatment Improves Cardiac Remodeling after Infarction by Targeting Myeloid Cells
| Autor: | Philipp A. Lang, Heiko Reffelt, Christina Alter, Rianne Nederlof, André Heinen, Priyadarshini Panjwani, Jelena Vasilevska, Annika Raupach, Maria Grandoch, Tengis Tschaidse, Johannes Boy, Anne Petz, Karl Köhrer, André Spychala, Axel Gödecke, Patrick Petzsch, Jens W. Fischer, Stefanie Gödecke |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Cardiac function curve
endocrine system Myeloid medicine.medical_treatment Macrophage polarization Myocardial Infarction Infarction Real-Time Polymerase Chain Reaction Receptor IGF Type 1 03 medical and health sciences Mice 0302 clinical medicine Drug Discovery Genetics Medicine Animals Myeloid Cells Myocardial infarction cardiovascular diseases Insulin-Like Growth Factor I Receptor Molecular Biology 030304 developmental biology Insulin-like growth factor 1 receptor Pharmacology Mice Knockout 0303 health sciences business.industry Growth factor medicine.disease Flow Cytometry Mice Inbred C57BL medicine.anatomical_structure Echocardiography 030220 oncology & carcinogenesis Cancer research Molecular Medicine Original Article business hormones hormone substitutes and hormone antagonists |
| Popis: | Insulin-like growth factor 1 (IGF1) is an anabolic hormone that controls the growth and metabolism of many cell types. However, IGF1 also mediates cardio-protective effects after acute myocardial infarction (AMI), but the underlying mechanisms and cellular targets are not fully understood. Here we demonstrate that short-term IGF1 treatment for 3 days after AMI improved cardiac function after 1 and 4 weeks. Regional wall motion was improved in ischemic segments, scar size was reduced, and capillary density increased in the infarcted area and the border zone. Unexpectedly, inducible inactivation of the IGF1 receptor (IGF1R) in cardiomyocytes did not attenuate the protective effect of IGF1. Sequential cardiac transcriptomic analysis indicated an altered myeloid cell response in the acute phase after AMI, and, notably, myeloid-cell Igf1r(−/−) mice lost the protective IGF1 function after I/R. In addition, IGF1 induced an M2-like anti-inflammatory phenotype in bone marrow-derived macrophages and enhanced the number of anti-inflammatory macrophages in heart tissue on day 3 after AMI in vivo. In summary, modulation of the acute inflammatory phase after AMI by IGF1 represents an effective mechanism to preserve cardiac function after I/R. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|