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Establishment and maintenance of blood–lymph separation

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Abstract

Hippocratic Corpus, a collection of Greek medical literature, described the functional anatomy of the lymphatic system in the fifth century B.C. Subsequent studies in cadavers and surgical patients firmly established that lymphatic vessels drain extravasated interstitial fluid, also known as lymph, into the venous system at the bilateral lymphovenous junctions. Recent advances revealed that lymphovenous valves and platelet-mediated hemostasis at the lymphovenous junctions maintain life-long separation of the blood and lymphatic vascular systems. Here, we review murine models that exhibit failure of blood–lymph separation to highlight the novel mechanisms and molecular targets for the modulation of lymphatic disorders. Specifically, we focus on the transcription factors, cofactors, and signaling pathways that regulate lymphovenous valve development and platelet-mediated lymphovenous hemostasis, which cooperate to maintain blood–lymph separation.

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Acknowledgements

We gratefully acknowledge Zachary J. Milstone for critical reading of the article. C.M.T is supported by National Heart, Lung, and Blood Institute grants R01 HL141377 (to C.M.T). We apologize to our colleagues whose work could not be discussed due to space limitations.

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Authors and Affiliations

  1. Division of Cardiovascular Medicine, University of Massachusetts Medical School, The Albert Sherman Center, AS7-1047, 368 Plantation St, Worcester, MA, 01605, USA

    Harish P. Janardhan & Chinmay M. Trivedi

  2. Department of Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA

    Harish P. Janardhan & Chinmay M. Trivedi

  3. Department of Molecular, Cell, and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, 01605, USA

    Chinmay M. Trivedi

  4. The Li-Weibo Institute for Rare Diseases Research, University of Massachusetts Medical School, Worcester, MA, 01605, USA

    Chinmay M. Trivedi

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Janardhan, H.P., Trivedi, C.M. Establishment and maintenance of blood–lymph separation. Cell. Mol. Life Sci. 76, 1865–1876 (2019). https://doi.org/10.1007/s00018-019-03042-3

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