Lymphangiogenesis via VEGF-C/VEGFR-3 Pathway Following Myocardial Ischemia-Reperfusion Injury due to Myocardial Infarction

Melanie L. Painter

Introduction. Myocardial infarction results from insufficient blood flow to the heart. Endogenous lymphangiogenesis is initiated after myocardial infarction and serves a protective role against the development of heart failure by reducing inflammation and edema.3 Vascular Endothelial Growth Factor C (VEGF-C) and VEGF Receptor 3 (VEGFR-3) both increase in expression in the 7 days following ischemic injury; the VEGF-C/VEGFR-3 pathway promotes lymphangiogenesis.4,8 Prolonged increased edema and inflammation in myocardial tissues increases the development of fibrosis.6 Fibrotic myocardial tissue negatively impacts cardiac function following myocardial infarction ischemic injury.2,5,6 Iatrogenic VEGF-C administration following myocardial infarction could be useful given its ability to promote lymphangiogenesis.1 Methods. A mouse model using mice of a single sex is used to reduce the introduction of new variables into the experiments due to known sex differences in cardiovascular disease. Coronary artery occlusion followed by reperfusion is performed to mimic the process that occurs during a myocardial infarction. Manipulations of lymphangiogenesis include both inhibition of the VEGF-C/VEGFR-3 pathway as well as stimulation. Cardiac function is assessed using echocardiography and lymphatic markers were screened for using immunohistochemistry. Results. Functional recovery after myocardial infarction is correlated with increased VEGF-C/VEGFR-3 signaling following injury.5,7 Aberrations of endogenous lymphangiogenesis correlate with increased adverse cardiac remodeling and increased risk of developing heart failure following myocardial ischemic injury.1,3,6  Conclusions. Iatrogenic VEGF-C administration following myocardial ischemic injury is correlated with improved cardiac functional recovery and reduced adverse remodeling. The ability to promote functional recovery after myocardial infarction will decrease the rate of development of heart failure and thus improve quality of life and decrease healthcare costs.

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