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BBB Seminar: Anatoliy A. Gashev

Mechanisms of lymph transport and their aging

Anatoliy A. Gashev
Department of Systems Biology and Translational Medicine, College of Medicine, Texas A&M Health Science Center, Temple, TX, USA

Effective lymph flow is crucial for fluid and macromolecule homeostasis, fat absorption, and immunity. Studies of the last decade significantly advanced the understanding of the basic mechanisms controlling lymph flow, and therefore all processes indicated above. Aging alters all of these functions, however, even the status of contractility and flow in aged lymph vessels is not well characterized. The role of oxidative stress and chronic inflammation as risk factors for aging of lymph vessels is unknown.

The major units of lymphatic vessels, lymphangions, pump lymph in a self-regulatory mode by constantly adjusting their contractions to the complicated combinations of lymph pressure and flows. Phasic contraction-generated spikes of nitric oxide, and imposed-flow generated shifts in basal levels of NO play pivotal role in the adaptive regulation of lymph pumping. Regional variability in regulatory mechanisms of lymph flow relates to the existence of the additional, not completely discovered regulatory pathways involved into stretch- and flow-dependent modulation of lymphatic contractility. We found weakening of the lymphatic pump in isolated aged mesenteric lymph vessels (MLV) including diminished tone, contraction amplitude, and frequency with corresponding decrease in their minute productivity. Application of L-NAME is able to enhance contractility of aged MLV. Observations in situ revealed a greater degree of the contractile inhibition of aged MLV related to excessive NO in a natural tissue environment. Data demonstrate diminished ability of the aged MLV to resist to oxidative stress: decreased SOD activity referred to diminished expression of its Cu/Zn isoform. High levels of superoxide anions and increased levels of lipid peroxidation confirmed in aged MLV. The experimental data confirm the feasibility and effectiveness of culture of the isolated lymphatic vessels and their adenoviral transfection (GFP and SERCA2a).

Cumulatively, the recent advancements of the field support the concept of lymph flow as a constant interplay of the action of extrinsic and intrinsic lymph pumps with a key role of phasic lymphatic contractility, and demonstrate the complexity of these mechanisms. Latest findings demonstrate links between age-related oxidative stress, inflammation and functional disturbances in aged MLV. Results of in vivo studies demonstrate the potential to maintain normal lymphatic transport function in elderly by correction of aged-induced environmental changes in tissues. Modern research developments provide powerful tools to lymphologists to target genes involved in regulation of lymph transport.

Host: Helge Wiig, Department of Biomedicine