The Saban Research Institute of Children's Hospital Los Angeles, Los Angeles, United States
Xidi Feng
The Saban Research Institute of Children's Hospital Los Angeles, Los Angeles, United States
Guqin Mo
The Saban Research Institute of Children's Hospital Los Angeles, Los Angeles, United States
Antonio Aguayo
The Saban Research Institute of Children's Hospital Los Angeles, Los Angeles, United States
Jessi Villafuerte
The Saban Research Institute of Children's Hospital Los Angeles, Los Angeles, United States; Department of Biology, California State University of San Bernardino, San Bernardino, United States
Tyler Yoshida
The Saban Research Institute of Children's Hospital Los Angeles, Los Angeles, United States; Department of Biological Sciences, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, United States
Caroline A Pearson
Department of Neurobiology, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States
Institute of Cardiovascular Organogenesis and Regeneration, Faculty of Medicine, University of Münster, Münster, Germany; CiM Cluster of Excellence (EXC1003 CiM), University of Münster, Münster, Germany
The Saban Research Institute of Children's Hospital Los Angeles, Los Angeles, United States; Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, United States; Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, United States
The cardiac lymphatic vascular system and its potentially critical functions in heart patients have been largely underappreciated, in part due to a lack of experimentally accessible systems. We here demonstrate that cardiac lymphatic vessels develop in young adult zebrafish, using coronary arteries to guide their expansion down the ventricle. Mechanistically, we show that in cxcr4a mutants with defective coronary artery development, cardiac lymphatic vessels fail to expand onto the ventricle. In regenerating adult zebrafish hearts the lymphatic vasculature undergoes extensive lymphangiogenesis in response to a cryoinjury. A significant defect in reducing the scar size after cryoinjury is observed in zebrafish with impaired Vegfc/Vegfr3 signaling that fail to develop intact cardiac lymphatic vessels. These results suggest that the cardiac lymphatic system can influence the regenerative potential of the myocardium.
