Study of the therapeutic benefit of cationic copolymer administration to vascular endothelium under mechanical stress

Kristina Giantsos-Adams, Veronica Lopez-Quintero, Pavla Kopeckova, Jindrich Kopecek, John M. Tarbell, Randal Dull

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Pulmonary edema and the associated increases in vascular permeability continue to represent a significant clinical problem in the intensive care setting, with no current treatment modality other than supportive care and mechanical ventilation. Therapeutic compound(s) capable of attenuating changes in vascular barrier function would represent a significant advance in critical care medicine. We have previously reported the development of HPMA-based copolymers, targeted to endothelial glycocalyx that are able to enhance barrier function. In this work, we report the refinement of copolymer design and extend our physiological studies to demonstrate that the polymers: 1) reduce both shear stress and pressure-mediated increase in hydraulic conductivity, 2) reduce nitric oxide production in response to elevated hydrostatic pressure and, 3) reduce the capillary filtration coefficient (Kfc) in an isolated perfused mouse lung model. These copolymers represent an important tool for use in mechanotransduction research and a novel strategy for developing clinically useful copolymers for the treatment of vascular permeability.

Original languageEnglish (US)
Pages (from-to)288-294
Number of pages7
JournalBiomaterials
Volume32
Issue number1
DOIs
StatePublished - Jan 1 2011
Externally publishedYes

Keywords

  • Acute respiratory distress syndrome
  • Endothelium
  • Mechanotransduction
  • Nitric oxide
  • Vascular tone and reactivity

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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