Abstract 10832: Adiponectin Stimulates Lymphangiogenesis and Ameliorates Secondary Lymphedema
Background: The lymphatic vascular system is linked with various pathological processes including tumor metastasis and lymphedema. Obesity is the major risk factor for secondary lymphedema due to the obstruction of lymphatic system. Adiponectin is an adipose-derived plasma protein whose concentration is downregulated in association with obesity-related disorders. Here, we investigated the effects of adiponectin on lymphatic vessel growth and lymphedema in a mouse model and assessed its potential mechanism.
Methods and Results: A mouse model of lymphedema was created by ablation of tail surface lymphatic network, and the tail diameter was measured to estimate lymphedema at day 28 after induction of lymphedema. Lymphatic vessels were analyzed by immunohistochemical staining for LYVE-1 and podoplanin. Adiponectin-knockout (APN-KO) mice (n=7) showed a greater tail thickness compared with wild-type (WT) mice (n=12) (p<0.05), which was accompanied by a lower number of lymphatic vessels in the injured tails (p<0.05). Systemic administration of adenoviral vectors encoding adiponectin to WT mice led to decrease in tail thickness and increase in lymphatic vessel density in the lesion. In vitro experiments revealed that treatment with adiponectin protein promoted the differentiation of human lymphatic endothelial cells (LECs) into tube-like structures (p<0.01) when cultured on Matrigel matrix. Adiponectin protein also stimulated the phosphorylation of AMP-activated protein kinase (AMPK) and endothelial nitric oxide synthesis (eNOS) in LECs. Furthermore, blockade of AMPK and eNOS activation cancelled the adiponectin-stimulated increase in LEC differentiation.
Conclusions: Our data clearly demonstrate that adiponectin promotes lymphatic vessel growth and ameliorates secondary lymphedema, at least in part, through activation of the AMPK-eNOS pathway within lymphatic endothelial cells.
- © 2012 by American Heart Association, Inc.