Lymphedema and therapeutic lymphangiogenesis

Abstract

Lymphedema is a disorder of the lymphatic vascular system characterized by impaired lymphatic return and swelling of the extremities. Lymphedema is divided into primary and secondary forms based on the underlying etiology. Despite substantial advances in both surgical and conservative techniques, therapeutic options for the management of lymphedema are limited. Although rarely lethal, lymphedema is a disfiguring and disabling condition with an associated decrease in the quality of life. The recent impressive expansion of knowledge on the molecular mechanisms governing lymphangiogenesis provides new possibilities for the treatment of lymphedema. This review highlights the lymphatic biology, the pathophysiology of lymphedema, and the therapeutic lymphangiogenesis using hepatocyte growth factor.

Figure 1

Schematic diagram of the pathophysiology of lymphedema.

Figure 2

HGF lymphangiogenesis and gene therapy for lymphedema. (a) Effect of HGF plasmid on c-fos promoter activity in LEC. n = 4, *P < 0.05 versus control, VEGF165. (b) Typical western blot of ERK or Akt and phosphorylated ERK or Akt in cLEC before and 5, 10, and 15 minutes after treatment with human recombinant HGF (50 ng/mL). (c) Representative pictures of the fluorescent lymphography using PDE at day 7 and day 35 after surgery. “HGF” indicates human HGF plasmid (200 μg/0.1 mL) and “control” indicates GFP plasmid injection (200 μg/0.1 mL).