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Myocardial Infarction in Neonatal Mice, A Model of Cardiac Regeneration
Published on: May 24, 2016
The cardiac lymphatic system stimulates resolution of inflammation following myocardial infarction
Joaquim Miguel Vieira1, Sophie Norman1, Cristina Villa Del Campo1
1Burdon-Sanderson Cardiac Science Centre, Department of Physiology, Anatomy and Genetics.
Insights
Stimulating cardiac lymphangiogenesis with VEGF-C enhances immune cell clearance after myocardial infarction (MI). Targeting the lymphatic and immune cell axis may promote heart repair and reduce cardiac fibrosis.
Area of Science:
- Cardiovascular Biology
- Immunology
- Regenerative Medicine
Background:
- Myocardial infarction (MI) causes significant cardiomyocyte loss and leads to heart failure due to scar tissue formation and pathological remodeling.
- The innate immune system attempts to clear debris post-MI, but persistent inflammation and lack of cardiac regeneration result in fibrosis.
- Current treatments for MI are limited, highlighting the need for novel therapeutic strategies to promote heart repair.
Purpose of the Study:
- To investigate the role of cardiac lymphangiogenesis in modulating the immune response following MI.
- To determine if stimulating lymphangiogenesis with VEGF-C can improve post-MI inflammation resolution and cardiac function.
- To elucidate the mechanism involving LYVE-1 in immune cell trafficking through lymphatic vessels.
Main Methods:
- Utilized mouse models to study the effects of VEGF-C on cardiac lymphangiogenesis and immune cell clearance post-MI.
- Employed genetic deletion of Lyve1 to assess its role in leukocyte trafficking and inflammatory response.
- Analyzed immune cell infiltration, lymphatic vessel function, and cardiac remodeling using histological and functional assays.
Main Results:
- VEGF-C stimulation promoted cardiac lymphangiogenesis, enhancing the clearance of acute inflammation by trafficking immune cells to mediastinal lymph nodes (MLNs).
- This process was dependent on lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), which mediates leukocyte docking and transit.
- Deletion of Lyve1 exacerbated chronic inflammation and led to long-term deterioration of cardiac function after MI.
Conclusions:
- Targeting cardiac lymphangiogenesis and the lymphatic/immune cell axis represents a promising therapeutic strategy for post-MI recovery.
- Enhancing immune cell clearance via lymphatic vessels can mitigate chronic inflammation and improve cardiac function after myocardial infarction.
- LYVE-1 is crucial for the resolution of inflammation and prevention of cardiac dysfunction following MI.
Abstract:
Myocardial infarction (MI) arising from obstruction of the coronary circulation engenders massive cardiomyocyte loss and replacement by non-contractile scar tissue, leading to pathological remodeling, dysfunction, and ultimately heart failure. This is presently a global health problem for which there is no effective cure. Following MI, the innate immune system directs the phagocytosis of dead cell debris in an effort to stimulate cell repopulation and tissue renewal. In the mammalian adult heart, however, the persistent influx of immune cells, coupled with the lack of an inherent regenerative capacity, results in cardiac fibrosis. Here, we reveal that stimulation of cardiac lymphangiogenesis with VEGF-C improves clearance of the acute inflammatory response after MI by trafficking immune cells to draining mediastinal lymph nodes (MLNs) in a process dependent on lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1). Deletion of Lyve1 in mice, preventing docking and transit of leukocytes through the lymphatic endothelium, results in exacerbation of chronic inflammation and long-term deterioration of cardiac function. Our findings support targeting of the lymphatic/immune cell axis as a therapeutic paradigm to promote immune modulation and heart repair.
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