Jacob von Esebeck
Research Subjects
Jacob von Esebeck has a total of 22 co-authors. Here are the top co-authors by number of shared publications:
Carolin Lerchenmüller
Department of Cardiology, Angiology, Pulmonology, University Hospital Heidelberg, Heidelberg, Germany
1 shared publication- Christian David Sadik
Department of Dermatology, Allergy, and Venereology University of Lübeck Lübeck Germany
1 shared publication Christine Zürn
Department of Cardiology, University Heart Center, University Hospital Basel, Basel, Switzerland; Cardiovascular Research Institute Basel, University Heart Center, University Hospital Basel, Basel, Switzerland
1 shared publication- Daniel Duerschmied
First Department of Medicine University Medical Centre Mannheim, Medical Faculty Mannheim of the University of Heidelberg Mannheim Germany
1 shared publication - Harald F. Langer
Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, European Center for Angioscience (ECAS), Medical Faculty Mannheim, University Medical Centre Mannheim, Heidelberg University, Mannheim, Germany
1 shared publication Hellmut Augustin
Division of Vascular Oncology and Metastasis, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
1 shared publication
Latest Publications
- Open Access
Platelet C5aR1 mediates sex-specific ischemia-driven revascularization through estradiol-dependent CXCL4 release
Platelet activation is a central driver of myocardial infarction. The complement anaphylatoxin C5a is abundantly generated during myocardial infarction, and its receptor C5aR1 is highly expressed on platelets. However, the functional role of platelet C5aR1 in myocardial infarction (MI) remains unknown. Here, we show that platelet&[ndash]expressed C5aR1 critically amplifies thromboinflammatory cardiac injury by promoting platelet&[ndash]mediated neutrophil activation after MI. Platelet&[ndash]specific C5aR1 deletion reduced infarct size, fibrosis, and adverse remodeling while enhancing neovascularization and preserving cardiac function. Mechanistically, cell&[ndash]specific C5aR1 deletion markedly reduced myocardial platelet&[ndash]neutrophil accumulation and neutrophil extracellular trap (NET) formation, while circulating platelet&[ndash]neutrophil complexes were increased. Ex vivo, C5a&[ndash]stimulated platelets robustly induced NET release from neutrophils in a platelet C5aR1&[ndash] and CXCL4&[ndash]dependent manner, whereas platelets lacking C5aR1 failed to trigger NET formation. Pharmacological C5aR1 inhibition with PMX205 phenocopied the genetic platelet&[ndash]specific deletion, resulting in comparable cardioprotection. Together, these findings identify platelet C5aR1 as a druggable target of platelet&[ndash]neutrophil&[ndash]NET signaling that exacerbates myocardial injury and limits reparative healing after MI, highlighting platelet C5aR1 as a potential therapeutic approach to restrain thromboinflammation.
Open AccessPlatelet C5aR1 mediates sex-specific ischemia-driven revascularization through estradiol-dependent CXCL4 release
Platelet activation is a central driver of myocardial infarction. The complement anaphylatoxin C5a is abundantly generated during myocardial infarction, and its receptor C5aR1 is highly expressed on platelets. However, the functional role of platelet C5aR1 in myocardial infarction (MI) remains unknown. Here, we show that platelet&[ndash]expressed C5aR1 critically amplifies thromboinflammatory cardiac injury by promoting platelet&[ndash]mediated neutrophil activation after MI. Platelet&[ndash]specific C5aR1 deletion reduced infarct size, fibrosis, and adverse remodeling while enhancing neovascularization and preserving cardiac function. Mechanistically, cell&[ndash]specific C5aR1 deletion markedly reduced myocardial platelet&[ndash]neutrophil accumulation and neutrophil extracellular trap (NET) formation, while circulating platelet&[ndash]neutrophil complexes were increased. Ex vivo, C5a&[ndash]stimulated platelets robustly induced NET release from neutrophils in a platelet C5aR1&[ndash] and CXCL4&[ndash]dependent manner, whereas platelets lacking C5aR1 failed to trigger NET formation. Pharmacological C5aR1 inhibition with PMX205 phenocopied the genetic platelet&[ndash]specific deletion, resulting in comparable cardioprotection. Together, these findings identify platelet C5aR1 as a druggable target of platelet&[ndash]neutrophil&[ndash]NET signaling that exacerbates myocardial injury and limits reparative healing after MI, highlighting platelet C5aR1 as a potential therapeutic approach to restrain thromboinflammation.