The Unresolved Pathophysiology of Lymphedema.

Syaza Hazwany Azhar,Veronique Angeli,Bien-Keem Tan,Hwee Ying Lim

doi:10.3389/fphys.2020.00137

Syaza Hazwany Azhar, Veronique Angeli + Show 2 more

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https://doi.org/10.3389/fphys.2020.00137

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Abstract

Lymphedema is the clinical manifestation of impaired lymphatic transport. It remains an under-recognized and under-documented clinical condition that still lacks a cure. Despite the substantial advances in the understanding of lymphatic vessel biology and function in the past two decades, there are still unsolved questions regarding the pathophysiology of lymphedema, especially in humans. As a consequence of impaired lymphatic drainage, proteins and lipids accumulate in the interstitial space, causing the regional tissue to undergo extensive and progressive architectural changes, including adipose tissue deposition and fibrosis. These changes are also associated with inflammation. However, the temporal sequence of these events, the relationship between these events, and their interplay during the progression are not clearly understood. Here, we review our current knowledge on the pathophysiology of lymphedema derived from human and animal studies. We also discuss the possible cellular and molecular mechanisms involved in adipose tissue and collagen accumulation during lymphedema. We suggest that more studies should be dedicated to enhancing our understanding of the human pathophysiology of lymphedema to pave the way for new diagnostic and therapeutic avenues for this condition.

Highlights

Specialty section: This article was submitted to Lipid and Fatty Acid Research, a section of the journal Frontiers in PhysiologyReceived: 13 December 2019 Accepted: 11 February 2020 Published: 17 March 2020Citation: Azhar SH, Lim HY, Tan B-K and Angeli V (2020) The Unresolved Pathophysiology of Lymphedema.Front
Methods to diagnose lymphedema have primarily focused on the detection of edema, lymphatic vessel transport, and lymph flow, until the recent advances in our knowledge of disease pathophysiology prompted the development of methods to assess tissue transformation including fibrosis and fat deposition (O’Donnell et al, 2017)
Lymphedema is characterized by several pathophysiological events, including lymph stasis, lymphatic vessel remodeling and dysfunction, inflammation, adipose tissue deposition, and fibrosis

Summary

Introduction

Specialty section: This article was submitted to Lipid and Fatty Acid Research, a section of the journal Frontiers in PhysiologyReceived: 13 December 2019 Accepted: 11 February 2020 Published: 17 March 2020Front. Lymphedema is a chronic and progressive disease arising from impaired lymphatic drainage causing the accumulation of interstitial fluid which results in tissue swelling (Rockson, 2001). Chy mice, a mouse model of lymphedema, due to heterozygous inactivating mutations in the vascular endothelial growth factor receptor 3, developed abnormal subcutaneous fat deposition, especially in edematous subcutaneous adipose tissue close to dysfunctional hypoplastic lymphatic vessels (Karkkainen et al, 2001).

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