The role of the cardiac lymphatics in heart repair and regeneration
Heart attack or myocardial infarction (MI) triggers an immune response, whereby phagocytic cells remove dead tissue and assist with subsequent repair. High load and persistence of immune cells, however, contributes to further fibrosis, pathological remodelling and ultimately progression to heart failure.
We have shown that the adult cardiac lymphatics traffic macrophages to draining mediastinal lymph nodes post-MI, to effect optimal repair and improve function. We are currently investigating which subsets of cleared macrophages correlate with improved outcome. We have further investigated their role across the regenerative window in neonatal mice (post-natal days 1-7; P1-P7). Normal lymphatic growth and sprouting is evident in intact neonatal hearts until P16, which coincides with a transition in lymphatic endothelial cell junctions from “zipper” (impermeable) to “button”-type (permeable) junctions. Moreover, the response to injury is significantly altered, with decreased lymphangiogenesis and minimal clearance of macrophages in P1 compared to P7 mice, 7-days post-MI, consistent with the need to maintain a pro-regenerative population of macrophages in the P1 injured heart. To gain molecular insight into potentially altered lymphatic endothelium-macrophage interactions across this period, we have generated unbiased scRNA-Seq datasets from P1 versus P7 infarcted hearts and observe significant differences in cellular cross-talk. Finally, in mice lacking lymphatic endothelial receptor-1 (Lyve1), that exhibit impaired macrophage trafficking, we surprisingly observed impaired functional outcome in P1 mice 28-days post-MI. This suggests a distinct role for Lyve-1 in tissue resident macrophages during neonatal heart regeneration.
Further mechanistic studies may provide therapeutic insights into immunomodulation of the adult infarcted heart.
Date:
21 July 2025, 12:00
Venue:
Kennedy Institute of Rheumatology, Headington OX3 7FY
Venue Details:
Kennedy Lecture Theatre
Speaker:
Prof Paul Riley (Institute of Developmental and Regenerative Medicine, University of Oxford)
Organising department:
Kennedy Institute of Rheumatology
Organiser:
Magdalena Gross
Host:
Prof Jagdeep Nanchahal (Professor of Hand,Plastic and Reconstructive surgery)
Part of:
Kennedy Institute Seminars
Booking required?:
Not required
Audience:
Members of the University only
Editor:
Magdalena Gross
