Roles of Lymphatic Vessels in Cardiac Tissue Regeneration
Abstract
Tissue regeneration holds great promise of treating organ injuries and chronic diseases, including coronary heart disease. Heart failure is the global leading cause of death, and coronary heart disease is a major risk factor that accounts for 380,000 deaths annually in the United States. Consequently, there is an urgent need for novel therapeutic interventions to help improve heart regeneration. Zebrafish have remarkable regenerative capacity after traumatic injuries or diseases. Hence, we will take this unique opportunity to study molecular mechanisms of tissue regeneration in zebrafish and try to apply this knowledge to improve therapies for human patients. How lymphatic vessels affect tissue regeneration is not well understood. Myocardial edema decreases cardiac output and can cause the heart to form scar tissues, which affect the contractions. Despite these findings, the importance of the cardiac lymphatic system has been largely underappreciated. The classic roles of lymphatic vessels are for fluid homeostasis and immune response. We unexpectedly discovered that zebrafish cardiac lymphatic vessels can also carry blood. This novel finding suggests that zebrafish lymphatic vessels might be utilized to provide additional oxygen and nutrients to the cardiac muscle when they regenerate. Furthermore, cardiac lymphatic vessels can regulate immune cell trafficking, and clearance of immune responses is essential for heart regeneration. In this proposal, we will determine how lymphatic vessels modulate revascularization and immune cell clearance to affect cardiac tissue regeneration. Molecular mechanisms within this new paradigm might lead to the development of novel therapies for heart failure.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910359
Entities
People
- Ching-ling Lien
Organizations
- Children's Hospital Los Angeles
- United States Army