The Importance Of The Lymphatic System

3. Discussion

The lymphatic system is specialized in the uptake of lymph from the interstitial space, the absorption of dietary lipids from the small intestine, and immune surveillance [64]. Since lymphatic markers have been identified much later than markers of blood vessels, research in the lymphatic system is quite new compared to that in blood vasculature. The importance of lymphatic vessels in health and disease is still not well established. Towards this end, work of this thesis was aimed at identifying molecules that are specifically expressed in the lymphatic vessels. In transcriptomic data analysis comparing blood and lymph endothelial cells, CD36 was determined to be specifically upregulated in the LECs of HDMECs in the tube formation assay. Therefore, research was directed toward unraveling the role of CD36 in the lymph system in vitro and in vivo. In vitro assays showed that CD36 was required for migration and proliferation of LECs. Furthermore, the effects of this soluble scavenger receptor were also structurally and functionally analyzed in detail in the skin of CD36-null mice and WT littermates. In vivo experiments focused on the skin since cellular experiments were focused on the dermal LECs. The function of the dermal lymphatics was analyzed in three different assays. In skin uptake experiments, Evans blue and FITC dextran were injected intradermally and the uptake of the lymphatics were visualized. Since these uptake experiments were qualitative, a quantitative assay was sought to measure lymphatic function. In a report on Emilin-deficient mice, Evans blue was injected in the footpad, and lymph nodes were analyzed quantitatively if they had the same dye content [167]. However, this assay had a limited window to q...

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...of anti-VEGFR3-treated mice because lymphatics on the aortic wall were disturbed, pointing out the importance of lymphatic vessels in RCT [191].

In conclusion, this work brings out important biological aspects of lymphangiogenesis. It also highlights the role of aging on lymphatic function, determined by a new lymphatic uptake assay. In addition, data of the present thesis shows previously undetermined role of CD36 in adipocyte and lymphatic biology with a focus on aging assessed by a unique Western diet feeding protocol. Although results of high fat feeding implies that loss of CD36 can ameliorate obesity, this work suggests that such a treatment should be carefully considered before implementation. Furthermore, studies involving conditional loss of CD36 in adipocytes of different ages would specifically determine effects of loss of CD36 on metabolism and aging.