Mechanobiology of Lymphatic Vessels

Regulating Lymphatic Vasculature in Fibrosis: Understanding the Biology to Improve the Modeling

“…Much is known about the effects of biomechanical inputs (e.g., flow, stretch, interstitial pressure), because they have historically dominated the lymphatic narrative. [5] However, gaps still remain in the field of lymphatic vascular mechanobiology, because less attention has been placed on investigating the contributions of ECM stiffness, and much of the research to date focuses on lymphatics in embryonic development rather than disease. [60,96,97] As more studies emerge to focus on ECM stiffness and lymphatics under normal and pathological conditions, [104,107] the field will have a deeper, more comprehensive understanding of lymphatic mechanobiology.…”

“…However, evidence over the years has shown that lymphatic vasculature plays a more active role in physiological and pathophysiological conditions. [3,4] Moreover, the diverse origins of lymphatic vessels produce organ-and diseasespecific vascular growth, structures, and functions that put lymphatic vasculature in the spotlight as a potential therapeutic target, [4,5] especially for diseases or conditions with significant lymphatic involvement but no effective curative solutions.Lymphangiogenesis-new vessel growth (or sprouting) from existing lymphatic vessels-is a key participant in many natural and pathological processes in adult tissues (e.g., wound healing, inflammation, tumor metastasis, fibrosis). [6] As lymphatic capillaries grow and branch, they form dense vascular networks to increase the overall surface area available for interstitial fluid uptake.…”

“…However, evidence over the years has shown that lymphatic vasculature plays a more active role in physiological and pathophysiological conditions. [3,4] Moreover, the diverse origins of lymphatic vessels produce organ-and diseasespecific vascular growth, structures, and functions that put lymphatic vasculature in the spotlight as a potential therapeutic target, [4,5] especially for diseases or conditions with significant lymphatic involvement but no effective curative solutions.…”

Lymphangiogenesis and Lymphatic Barrier Dysfunction in Renal Fibrosis

“…Laminar shear stress (LSS) exists in straight long vessels, and oscillatory SS is generated when fluid is disturbed at branch points [19]. Barrier function of the lymphatic endothelium increases with enhanced laminar flow [20,21], mechanism of which may be related to the small GTPase Rac1, which directs cytoskeletal reorganization at intercellular junctions [20]. Collagen fibers of LECs are attached to anchoring filaments, which can be pulled apart by increased interstitial pressure, resulting in opening of the LV lumen and enhancing uptake of lymph components [22].…”

“…This paracellular fluid transportation in lymphatic endothelium generates transmural SS. Decreased expression of tight junction, in the presence of elevated transmural SS, leads to increased permeability of endothelium [16,21]. Since transmural SS can help recruit CCR7 + immune cells into LVs and lymph nodes via promoting expression of cytokine CCL21 expression in LECs, it has been regarded as an important regulator of LEC function as well as an inflammatory cue at early stage for lymphatics [16].…”