4.7 Review

Biochemical and mechanical signals in the lymphatic vasculature

Journal

CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 78, Issue 16, Pages 5903-5923

Publisher

SPRINGER BASEL AG
DOI: 10.1007/s00018-021-03886-8

Keywords

Mechanotransduction; Shear stress; Lymphatic vascular development; Valve; Lymphatic endothelial cells; PROX1; FOXC2; GATA2; Wnt; YAP; TAZ

Funding

  1. NIH/NHLBI [R01HL131652, R01HL133216]
  2. NIH/NIGMS COBRE [P20 GM103441]
  3. Oklahoma Center for Adult Stem Cell Research [4340]
  4. American Heart Association [19POST34380819]

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The lymphatic vasculature is crucial for maintaining interstitial fluid balance, regulating lipid assimilation, and inflammatory response. Defects in lymphatic vessels or valves can lead to fluid accumulation, metabolic disorders, and inflammation. Studies have identified molecules and mechanical signals that play key roles in the development and function of the lymphatic vasculature, providing insights for potential therapies.
Lymphatic vasculature is an integral part of the cardiovascular system where it maintains interstitial fluid balance. Additionally, lymphatic vasculature regulates lipid assimilation and inflammatory response. Lymphatic vasculature is composed of lymphatic capillaries, collecting lymphatic vessels and valves that function in synergy to absorb and transport fluid against gravitational and pressure gradients. Defects in lymphatic vessels or valves leads to fluid accumulation in tissues (lymphedema), chylous ascites, chylothorax, metabolic disorders and inflammation. The past three decades of research has identified numerous molecules that are necessary for the stepwise development of lymphatic vasculature. However, approaches to treat lymphatic disorders are still limited to massages and compression bandages. Hence, better understanding of the mechanisms that regulate lymphatic vascular development and function is urgently needed to develop efficient therapies. Recent research has linked mechanical signals such as shear stress and matrix stiffness with biochemical pathways that regulate lymphatic vessel growth, patterning and maturation and valve formation. The goal of this review article is to highlight these innovative developments and speculate on unanswered questions.

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