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

Paper ID Volume ID Publish Year Pages File Format Full-Text
8425 589 2011 7 PDF Available
Title
Study of the therapeutic benefit of cationic copolymer administration to vascular endothelium under mechanical stress
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.

Keywords
Endothelium; Acute respiratory distress syndrome; Mechanotransduction; Nitric oxide; Vascular tone and reactivity
First Page Preview
Study of the therapeutic benefit of cationic copolymer administration to vascular endothelium under mechanical stress
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 32, Issue 1, January 2011, Pages 288–294
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering