Abstract 14344: Reduced Lymphatic Density in Skeletal Muscles in Human and Experimental Peripheral Artery Disease
Background: Peripheral Artery Disease (PAD) is most frequently caused by lower extremity atherosclerosis that results in arterial obstruction. Little is known about lymphangiogenesis and lymphatic vessel density in PAD patients. The Vascular Endothelial Growth Factor Receptor-3 (VEGFR-3) is a diagnostic marker of lymph vessels and this receptor is activated by VEGF. It is known that VEGF is upregulated under ischemic conditions. Hence we hypothesized that PAD subjects would have a greater lymphatic vessel density compared to healthy individuals.
Methods and Results: We obtained gastrocnemius (GA) skeletal muscle biopsies from patients with PAD (n=19) and healthy individuals (n=13) who served as controls. Immunohistochemical staining with anti-LYVE-1 (Lymphatic Vascular Endothelial Marker-1) antibody, a marker for lymphatic vessels, was performed and the number of LYVE-1 positive vessels per muscle fiber in each slide was determined. The average of number of lymphatic vessels per muscle fiber was lower in patients with PAD (0.07 ± 0.05) compared to healthy controls (0.15 ± 0.12), p=0.04. In a mouse model of PAD, the number of lymphatic vessels per muscle fiber was lower in ischemic leg GA (0.18 ± 0.04) when compared with non-ischemic leg GA (0.25 ± 0.03), p=0.003. We also found that VEGF-C, the ligand specific for lymphangiogenesis, was lower (p=0.005 on day 14 post-ischemia, p=0.02 on day 28 post ischemia) in ischemic versus non-ischemic muscles on western blot quantification in the PAD mouse model.
Conclusion: Lymphatic vessel density and lymphangiogenesis were lower in both human subjects and in a mouse model of peripheral artery disease compared to controls. These findings suggest reduction in lymph formation due to decreased blood flow in PAD and warrant further investigation since they may have clinical implications for PAD management.
- © 2013 by American Heart Association, Inc.