Ultrasound-guided transfection of claudin-5 improves lung endothelial barrier function in lung injury without impairing innate immunity

Author:

Sanwal Rajiv12,Mintsopoulos Victoria2,Ditmans Mihails2,Lang Alice2,Latreille Elyse12,Ghaffari Siavash2,Khosraviani Negar12,Karshafian Raffi34,Leong-Poi Howard2,Hwang David M.5,Brochard Laurent26ORCID,Goffi Alberto26,Slutsky Arthur S.26,Lee Warren L.1246ORCID

Affiliation:

1. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada

2. Keenan Research Center for Biomedical Science, St. Michael’s Hospital, Toronto, Ontario, Canada

3. Department of Physics, Toronto Metropolitan University, Toronto, Ontario, Canada

4. Institute for Biomedical Engineering, Science and Technology (iBEST), Toronto, Ontario, Canada

5. Department of Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada

6. Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada

Abstract

Acute respiratory distress syndrome is characterized by spatial heterogeneity, with severely injured lung regions adjacent to relatively normal areas. This makes targeting treatment to the injured regions difficult. Here we use thoracic ultrasound and intravenous microbubbles (USMBs) to direct gene transfection specifically to injured lung regions. Transfection of the tight junction protein claudin-5 improved oxygenation and decreased vascular leakage without impairing innate immunity. These findings suggest that USMB is a novel treatment for ARDS.

Funder

Canada Research Chairs

Gouvernement du Canada | Canadian Institutes of Health Research

Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada

Publisher

American Physiological Society

Subject

Cell Biology,Physiology (medical),Pulmonary and Respiratory Medicine,Physiology

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