Seminar Paul Riley
Dr. Paul Riley
BHF Professor of Regenerative Medicine & Chair of Development and Cell Biology, Department of Physiology, Anatomy and Genetics, University of Oxford
Title: The cardiac lymphatic system: development and response to injury
Abstract: We adopt the paradigm of understanding how the heart develops during pregnancy as a first principal to inform on adult heart repair and regeneration. Here we describe the development of the cardiac lymphatic vessels and exploit their ability to respond to injury in the adult setting to improve outcome. In contrast to the prevailing dogma for systemic lymphatics, the cardiac lymphatic vessels have a heterogeneous cellular origin, whereby formation of at least part of the cardiac lymphatic network is independent of sprouting from veins. Multiple cre-lox based lineage tracing revealed a potential contribution from the hemogenic endothelium during development and discrete lymphatic endothelial progenitor populations were confirmed by conditional knockout of Prox1 in Tie2+ and Vav1+ compartments. In the adult heart, myocardial infarction (MI) promoted a significant lymphangiogenic response, which was augmented by treatment with VEGF-C, resulting in improved cardiac function. These data prompt the re-evaluation of a century-long debate on the origin of lymphatic vessels and suggest that invoking developmental lymphangiogenesis may represent a therapeutic target to promote cardiac repair following injury.
Host: Jiejia Xu