JAHA 2018.pdf

<p>Background-—Lymphatic vessels interconnect with blood vessels to form an elaborate system that aids in the control of tissue</p> <p>pressure and edema formation. Although the lymphatic system has been known to exist in a heart, little is known about the role the</p> <p>cardiac lymphatic system plays in the development of heart failure.</p> <p>Methods and Results-—Mice (C57BL/6J, male, 8 to 12 weeks of age) were subjected to either myocardial ischemia or myocardial</p> <p>ischemia and reperfusion for up to 28 days. Analysis revealed that both models increased the protein expression of vascular</p> <p>endothelial growth factor C and VEGF receptor 3 starting at 1 day after the onset of injury, whereas a significant increase in lymphatic</p> <p>vessel density was observed starting at 3 days. Further studies aimed to determine the consequences of inhibiting the endogenous</p> <p>lymphangiogenesis response on the development of heart failure. Using 2 different pharmacological approaches, we found that</p> <p>inhibiting VEGF receptor 3 with MAZ-51 and blocking endogenous vascular endothelial growth factor C with a neutralizing antibody</p> <p>blunted the increase in lymphatic vessel density, blunted lymphatic transport, increased inflammation, increased edema, and</p> <p>increased cardiac dysfunction. Subsequent studies revealed that augmentation of the endogenous lymphangiogenesis response with</p> <p>vascular endothelial growth factor C treatment reduced inflammation, reduced edema, and improved cardiac dysfunction.</p> <p>Conclusions-—These results suggest that the endogenous lymphangiogenesis response plays an adaptive role in the development</p> <p>of ischemic-induced heart failure and supports the emerging concept that therapeutic lymphangiogenesis is a promising new</p> <p>approach for the treatment of cardiovascular disease.</p>