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.
- Aspelund A, Robciuc MR, Karaman S, Makinen T, Alitalo K. Lymphatic System in Cardiovascular Medicine. Circulation Research. 2016;118(3):515-530. doi:10.1161/circresaha.115.306544.
- Henri O, Pouehe C, Houssari M, et al. Selective Stimulation of Cardiac Lymphangiogenesis Reduces Myocardial Edema and Fibrosis Leading to Improved Cardiac Function Following Myocardial Infarction. Circulation. 2016;133(15):1484-1497. doi:10.1161/circulationaha.115.020143
- Huang L-H, Lavine KJ, Randolph GJ. Cardiac Lymphatic Vessels, Transport, and Healing of the Infarcted Heart. JACC: Basic to Translational Science. 2017;2(4):477-483. doi:10.1016/j.jacbts.2017.02.005.
- Oduk Y, Zhu W, Kannappan R, et al. VEGF nanoparticles repair the heart after myocardial infarction. American Journal of Physiology-Heart and Circulatory Physiology. 2017;314(2):278-284. doi:10.1152/ajpheart.00471.2017
- Shimizu Y, Polavarapu R, Eskla KL, et al. Impact of Lymphangiogenesis on Cardiac Remodeling After Ischemia and Reperfusion Injury. Journal of the American Heart Association. 2018;7(19). doi:10.1161/jaha.118.009565.
- Westman PC, Lipinski MJ, Luger D, et al. Inflammation as a Driver of Adverse Left Ventricular Remodeling After Acute Myocardial Infarction. Journal of the American College of Cardiology. 2016;67(17):2050-2060. doi:10.1016/j.jacc.2016.01.073.
- Yang Y, Shi C, Hou X, et al. Modified VEGF targets the ischemic myocardium and promotes functional recovery after myocardial infarction. Journal of Controlled Release. 2015;213:27-35. doi:10.1016/j.jconrel.2015.06.036
- Zhao T, Zhao W, Meng W, Liu C, Chen Y, Gerling IC, et al. VEGF-C/ VEGFR-3 pathway promotes myocyte hypertrophy and survival in the infarcted myocardium. American Journal of Translational Research. 2015;7(4):697-709.