Molecular identity of arteries, veins, and lymphatics

J Vasc Surg. 2019 Jan;69(1):253-262. doi: 10.1016/j.jvs.2018.06.195. Epub 2018 Aug 25.

Abstract

Background: Arteries, veins, and lymphatic vessels are distinguished by structural differences that correspond to their different functions. Each of these vessels is also defined by specific molecular markers that persist throughout adult life; these markers are some of the molecular determinants that control the differentiation of embryonic undifferentiated cells into arteries, veins, or lymphatics.

Methods: This is a review of experimental literature.

Results: The Eph-B4 receptor and its ligand, ephrin-B2, are critical molecular determinants of vessel identity, arising on endothelial cells early in embryonic development. Eph-B4 and ephrin-B2 continue to be expressed on adult vessels and mark vessel identity. However, after vascular surgery, vessel identity can change and is marked by altered Eph-B4 and ephrin-B2 expression. Vein grafts show loss of venous identity, with less Eph-B4 expression. Arteriovenous fistulas show gain of dual arterial-venous identity, with both Eph-B4 and ephrin-B2 expression, and manipulation of Eph-B4 improves arteriovenous fistula patency. Patches used to close arteries and veins exhibit context-dependent gain of identity, that is, patches in the arterial environment gain arterial identity, whereas patches in the venous environment gain venous identity; these results show the importance of the host infiltrating cells in determining vascular identity after vascular surgery.

Conclusions: Changes in the vessel's molecular identity after vascular surgery correspond to structural changes that depend on the host's postsurgical environment. Regulation of vascular identity and the underlying molecular mechanisms may allow new therapeutic approaches to improve vascular surgical procedures.

Keywords: Angiogenesis; Arteriogenesis; Eph-B4; Ephrin-B2; Identity; Vasculogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Arteries / embryology
  • Arteries / metabolism*
  • Arteries / surgery
  • Biomarkers / metabolism*
  • COUP Transcription Factor II / genetics
  • COUP Transcription Factor II / metabolism
  • Ephrin-B2 / genetics
  • Ephrin-B2 / metabolism
  • Gene Expression Regulation, Developmental
  • Gestational Age
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Lymphangiogenesis
  • Lymphatic Vessels / embryology
  • Lymphatic Vessels / metabolism*
  • Lymphatic Vessels / surgery
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Neovascularization, Physiologic
  • Receptor, EphB4 / genetics
  • Receptor, EphB4 / metabolism
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism
  • Signal Transduction
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism
  • Vascular Endothelial Growth Factor Receptor-2 / genetics
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism
  • Vascular Surgical Procedures
  • Veins / embryology
  • Veins / metabolism*
  • Veins / surgery

Substances

  • Biomarkers
  • COUP Transcription Factor II
  • Ephrin-B2
  • Homeodomain Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Receptors, Notch
  • Tumor Suppressor Proteins
  • delta protein
  • prospero-related homeobox 1 protein
  • Receptor, EphB4
  • Vascular Endothelial Growth Factor Receptor-2