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Establishment and maintenance of blood–lymph separation

  • Harish P. Janardhan
  • Chinmay M. TrivediEmail author
Review

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.

Keywords

Lymphovenous valve Hemostasis Platelet Lymphatic development Lymph Blood 

Notes

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.

Compliance with ethical standards

Conflict of interest

The authors have declared that no conflict of interest exists.

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Division of Cardiovascular MedicineUniversity of Massachusetts Medical SchoolWorcesterUSA
  2. 2.Department of MedicineUniversity of Massachusetts Medical SchoolWorcesterUSA
  3. 3.Department of Molecular, Cell, and Cancer BiologyUniversity of Massachusetts Medical SchoolWorcesterUSA
  4. 4.The Li-Weibo Institute for Rare Diseases ResearchUniversity of Massachusetts Medical SchoolWorcesterUSA

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