Insufficient Lymph Drainage Causes Abnormal Lipid Accumulation and Vein Wall Degeneration

Objective: Previously, we analyzed human varicose veins (VV) using imaging mass spectrometry (IMS) and detected the abnormal accumulation of lipid molecules in the walls of VV, possibly due to insufficient lipid drainage by the lymphatic vessels. In this study, we created an animal model of lymphatic insufficiency to investigate the effects of insufficient lymph drainage on vein walls. Methods: In rats, the lymphatic collecting vessels surrounding the femoral vein were ligated on one side (the model tissue), which caused the local retention of lymphatic fluid in the perivascular tissue. The equivalent contralateral tissue was used as a control. A histological study of the femoral vein and the surrounding perivascular tissue was conducted. IMS was used to analyze the distribution of lipid molecules in the perivascular tissue. Results: Fourteen days after the procedure, the lymphatic vessels in the model tissue were significantly dilated. Furthermore, IMS revealed that the composition of the lipid molecules in the perivascular regions of the model tissue had altered. Compared with the control tissue, the model tissue exhibited marked perivascular accumulation of lysophosphatidylcholine (1-acyl 16:0), phosphatidylcholine (16:0/20:4), and triglycerides (52:2). Interestingly, the walls of the femoral veins running through the model tissue were 3.4-fold thicker than those of the femoral veins running through the control tissue. The number of tumor necrosis factor α-positive adipocytes was increased in the perivascular regions of the model tissue. Conclusion: The findings of this study indicated that the accumulation of lymphatic fluid due to insufficient lymph drainage changes the structure of vein walls, and such changes might be associated with chronic venous insufficiency. (This is a translation of Jpn J Phlebol 2015; 26: 227-235.).