Abstract 5883: Role of Myocardial Lymphangiogenesis in Hypertensive Heart Failure
Recent reports have emphasized the important role of inflammation in the pathophysiology of heart failure. Lymphatic system is important in immune responses. The vascular endothelial growth factor (VEGF)-C/VEGF-D/VEGF receptor (VEGFR)-3 signaling pathway is crucial for lymphangiogenesis. However, the roles of lymphatic vessels in myocardium remain unclear. This study was designed to examine the role of myocardial lymphangiogenesis in a murine model of hypertensive heart failure. Nine-week-old C57BL/6 mice were exposed to pressure over load produced by banding of the abdominal aorta (day 0). The hearts were fixed in 10% formalin, embedded in paraffin, sectioned, and analyzed, performing immunohistochemical staining on day 14, 28, 56, 77, and 105. We used the antibodies against VEGFR-3 or podoplanin which is specific for lymphatic vessels. In addition, we examined the effects of VEGF-C156S, lymphangiogenesis inducer, or VEGFR3-Fc, lymphangiogenesis blocker, on hemodynamics in the same model. Immunohistochemical staining for VEGFR-3 and podoplanin resulted in successful labeling of lymphatic capillaries in myocardium. Lymphatic vessels appeared in the myocardium on day 28. The number of lymphatic vessels was 4.8 ± 0.4 vessels/mm2, and lymphatic area was 1.4 ± 0.5%. In the chronic phase, lymphatic vessels were decreased. The number of lymphatic vessels was 2.4 ± 0.2 vessels/mm2, and lymphatic area was 0.4 ± 0.2%. VEGF-C156S and VEGFR3-Fc proteins were successfully expressed in myocardium. Myocardial lymphatic vessels were successfully determined by immunohistochemical staining. These findings provide new insights into the role of myocardial lymphangiogenesis in the pathophysiology of hypertensive heart failure, and suggest therapeutic benefits by modulating lymphangiogenesis in hypertensive heart failure.