Editors' ChoiceCardiovascular Disease

I heart lymphatics

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Science Translational Medicine  13 Apr 2016:
Vol. 8, Issue 334, pp. 334ec58
DOI: 10.1126/scitranslmed.aaf6936

Fluid builds up in the heart immediately after ischemia, or the temporary interruption of blood flow—something that happens after myocardial infarction (MI) or obstruction of cardiac lymphatics during surgery. The blockage of vessels or lymphatics, which return macromolecules and fluids from peripheral tissues, can have deleterious effects on cardiac function. However, the association of lymphatic insufficiency with MI-induced edema has remained underexplored. New evidence from Henri et al. reveals that lymphatic dysfunction in the heart occurs after injury and contributes to chronic myocardial edema and inflammation, leading to cardiac fibrosis and dysfunction. Such a linkage implicates the potential for therapeutic lymphangiogenesis (i.e., generation of lymphatic vessels) in the treatment of cardiovascular diseases.

The authors looked at cardiac and lymphatic function after the induction of MI in rats, using a combination of heart imaging tools, hemodynamic measurements, as well as tissue staining. They discovered decreased cardiac lymphatic transport resulting from remodeling of lymphatic vessels in the tissue lining the heart after MI. Negative remodeling and impaired lymphatic function were associated with increased heart inflammation, fibrosis, and dysfunction. Henri et al. hypothesized that stimulating lymphangiogenesis would be therapeutic. Indeed, application of vascular endothelial growth factor C delivered via albumin-alginate microparticles directly to the heart limited lymphatic and pathological tissue remodeling post-MI.

This study reveals a critical role for lymphatics in exacerbating cardiac pathology after MI and implies that genetic or acquired lymphangiogenic deficits may increase risk of chronic myocardial edema and cardiac dysfunction with myocardial ischemia. It also suggests the potential for growth factor­–based or other interventions that stimulate lymphangiogenesis to improve lymphatic function in the treatment of ischemic heart disease.

O. Henri et al., Selective stimulation of cardiac lymphangiogenesis reduces myocardial edema and fibrosis leading to improved cardiac function following myocardial infarction. Circulation 10.1161/CIRCULATIONAHA.115.020143 (2016). [Abstract]

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