Coronary Revascularization During Heart Regeneration Is Regulated by Epicardial and Endocardial Cues and Forms a Scaffold for Cardiomyocyte Repopulation
| Autor: | Sofia-Iris Bibli, Sri Teja Mullapuli, Rubén Marín-Juez, Kenneth D. Poss, Ingrid Fleming, Aosa Kamezaki, Christian S. M. Helker, Didier Y.R. Stainier, Hadil El-Sammak, Matthew J. Foglia |
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| Rok vydání: | 2019 |
| Předmět: |
Receptors
CXCR4 medicine.medical_specialty Heart Ventricles medicine.medical_treatment Neovascularization Physiologic Infarction Biology Revascularization Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Internal medicine Myocardial Revascularization medicine Animals Regeneration Myocytes Cardiac cardiovascular diseases Myocardial infarction Molecular Biology Zebrafish Endocardium Cell Proliferation 030304 developmental biology Wound Healing 0303 health sciences Heart Cell Biology Zebrafish Proteins Hypoxia (medical) medicine.disease biology.organism_classification Chemokine CXCL12 Apelin Vascular endothelial growth factor A cardiovascular system Cardiology Cues medicine.symptom Pericardium 030217 neurology & neurosurgery Signal Transduction Developmental Biology |
| Zdroj: | Dev Cell |
| ISSN: | 1534-5807 |
| Popis: | Defective coronary network function and insufficient blood supply are both cause and consequence of myocardial infarction. Efficient revascularization after infarction is essential to support tissue repair and function. Zebrafish hearts exhibit a remarkable ability to regenerate, and coronary revascularization initiates within hours of injury, but how this process is regulated remains unknown. Here we show that revascularization requires a coordinated multi-tissue response culminating with the formation of a complex vascular network available as a scaffold for cardiomyocyte repopulation. During a process we term “coronary-endocardial anchoring”, new coronaries respond by sprouting 1) superficially within the regenerating epicardium, and 2) intra-ventricularly towards the activated endocardium. Mechanistically, superficial revascularization is guided by epicardial Cxcl12-Cxcr4 signaling, and intra-ventricular sprouting by endocardial Vegfa signaling. Our findings indicate that the injury-activated epicardium and endocardium support cardiomyocyte replenishment initially through the guidance of coronary sprouting. Simulating this process in the injured mammalian heart should help its healing. |
| Databáze: | OpenAIRE |
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