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Biomimetic Microsystems for Blood and Lymphatic Vascular Research
Published in Hyun Jung Kim, Biomimetic Microengineering, 2020
At molecular levels, FOXC2, a member of the Forkhead/winged-helix family of transcription factors is one of the main players in the collecting lymphatic vessel maturation (Norrmen et al. 2009). In human, FOXC2 mutation causes lymphedema-distichiasis, a lymphatic stagnation featured by increased lymph backflow (Mellor et al. 2011). In mouse models, FOXC2 deficiency also showed dysregulated lymphatic valve formation and impaired mural cell coverage in the collecting lymphatic vessels during the maturation processes (Noon et al. 2006). Interestingly, the inactivation of the FOXC2 results in dilated lymphatic capillaries and ectopic coverage of mural cells on the lymphatic capillaries (de Mooij et al. 2009), suggesting that FOXC2 is critical for differential maturation of the initial and collecting lymphatic vessels. In lymphatic valve cells, FOXC2-calcineurin/NFATc1 signaling is activated and the loss of calcineurin at development results in lymphatic valve defects (Sabine and Petrova 2014). Besides, the gap junction protein CX37 is also known to be essential for the assembly of lymphatic valves (Kanady et al. 2015) (Figure 2.2b).
A fully coupled fluid-structure interaction model of the secondary lymphatic valve
Published in Computer Methods in Biomechanics and Biomedical Engineering, 2018
John T. Wilson, Lowell T. Edgar, Saurabh Prabhakar, Marc Horner, Raoul van Loon, James E. Moore
Solutes and fluid passively enter the lymphatic system through initial lymphatic vessels which eventually give rise to the collecting lymphatics, which differ from initial lymphatics in size as well as the presence of lymphatic muscle cells (LMCs) and secondary valves (Zawieja et al. 2011). The secondary lymphatic valves are bi-leaflet structures that serve to prevent retrograde flow. The leaflets consist of lymphatic endothelial cells (LECs) (Takada 1971; Vajda and Tomcsik 1971) with an extracellular matrix (ECM) composed of elastin and are almost entirely devoid of collagen (Rahbar et al. 2012). The valves are frequent throughout collecting vessels and function in a complex mechanical environment where the valve deflections are determined by fluid pressures upstream and downstream of the valve. Further, the forkhead transcription factor FOXC2 is highly expressed in LECs of the valve sinus where others have proposed the existence of complex flow patterns (Mellor et al. 2007; Sabine et al. 2015).