Endothelialization of arterial vascular grafts by circulating monocytes.

Randall J Smith, Bita Nasiri, Julien Kann, Donald Yergeau, Jonathan E Bard, Daniel D Swartz, Stelios T Andreadis
Author Information
  1. Randall J Smith: Department of Biomedical Engineering, University at Buffalo, State University of New York, Amherst, NY, 14260, USA.
  2. Bita Nasiri: Department of Chemical and Biological, University at Buffalo, State University of New York, Amherst, NY, 14260, USA.
  3. Julien Kann: Genomics and Bioinformatics Core, University at Buffalo, State University of New York, Amherst, NY, 14260, USA.
  4. Donald Yergeau: Genomics and Bioinformatics Core, University at Buffalo, State University of New York, Amherst, NY, 14260, USA. ORCID
  5. Jonathan E Bard: Genomics and Bioinformatics Core, University at Buffalo, State University of New York, Amherst, NY, 14260, USA. ORCID
  6. Daniel D Swartz: Angiograft LLC, Amherst, NY, 14260, USA.
  7. Stelios T Andreadis: Department of Biomedical Engineering, University at Buffalo, State University of New York, Amherst, NY, 14260, USA. sandread@buffalo.edu.

Abstract

Recently our group demonstrated that acellular tissue engineered vessels (A-TEVs) comprised of small intestinal submucosa (SIS) immobilized with heparin and vascular endothelial growth factor (VEGF) could be implanted into the arterial system of a pre-clinical ovine animal model, where they endothelialized within one month and remained patent. Here we report that immobilized VEGF captures blood circulating monocytes (MC) with high specificity under a range of shear stresses. Adherent MC differentiate into a mixed endothelial (EC) and macrophage (Mφ) phenotype and further develop into mature EC that align in the direction of flow and produce nitric oxide under high shear stress. In-vivo, newly recruited cells on the vascular lumen express MC markers and at later times they co-express MC and EC-specific proteins and maintain graft patency. This novel finding indicates that the highly prevalent circulating MC contribute directly to the endothelialization of acellular vascular grafts under the right chemical and biomechanical cues.

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Grants

  1. R01 HL151196/NHLBI NIH HHS
  2. F31 HL134323/NHLBI NIH HHS
  3. R01 HL086582/NHLBI NIH HHS

MeSH Term

Animals
Arteries
Blood Vessel Prosthesis
Cardiovascular System
Cell Differentiation
Cell Proliferation
Endothelium
Heparin
Macrophages
Models, Animal
Monocytes
Sheep
Stress, Mechanical
Tissue Engineering
Vascular Endothelial Growth Factor A

Chemicals

Vascular Endothelial Growth Factor A
Heparin