Title:
Lymphatic vessel mechanics: a clue towards treating lymphedema
Lymphatic vessel mechanics: a clue towards treating lymphedema
Author(s)
Mukherjee, Anish
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Abstract
Lymphedema, a debilitating disease characterized by a disfiguring swelling of the extremities, affects
nearly 140 to 250 million people worldwide. In the US the primary cause of lymphedema is breast
cancer related surgery and it can affect about 70% of the patients depending on the nature of the
surgery and any secondary insult. The exact pathogenesis of lymphedema is not clear and diagnosis
usually happens at a late stage. Further, the treatment of lymphedema is rarely corrective and
focuses more on disease management.
One of the primary causes of lymphedema is suspected to be dysfunctions in the lymphatic system.
The lymphatic system is a complex network of vessels and nodes that plays an important role in the
maintenance of the tissue fluid balance in the body. Lymphatic vessels have been shown to modulate
their contractility in response to mechanical forces like transmural pressure and flow induced shear stress (referred to as shear sensitivity). Reduction in shear sensitivity of the lymphangions is
suspected to be a major cause of lymphatic dysfunction and, in turn, lymphedema. Hence, it is
important to understand how the shear sensitivity of the lymphatic vessel affects the contractility of
the vessel in response to the dynamic mechanical microenvironment within the lymphatic vessels.
The molecular mechanisms involved in the shear sensitivity of lymphangions also need to be
delineated. Finally it is important to investigate whether the lymphatic vessel function can be
optimized through mechanical stimulation.
These central questions will be approached from three different length scales; in vitro through
molecular mechanisms of mechanosensitivity, ex vivo through functional response of lymphatic
vessels to oscillatory shear stress and in vivo through reduction in swelling in animals using external
oscillatory mechanical stimuli. These aims will lead to the identification of some of the molecular
pathways involved in the transduction of shear stress by lymphatic endothelial cells and will motivate
studies into pharmacological modulation of lymphatic contractility to maximize its response to
oscillatory shear stresses. Quantifying the effect of externally applied pressure, such as those applied
during physiotherapy, will provide a scientific basis for enhancing lymphatic system function noninvasively.
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Date Issued
2018-11-07
Extent
03:11 minutes
Resource Type
Moving Image
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