Dysregulation of endothelial cell connexin-43 localisation in response to doxorubicin

Veerman, Ben and McGivern, Samantha-Joe and Dempsie, Yvonne and Martin, Patricia E M and Johnston, Blair and Currie, Susan and Cunningham, Margaret Rose (2020) Dysregulation of endothelial cell connexin-43 localisation in response to doxorubicin. Heart, 106 (1). 11. ISSN 1468-201X

[img]
Preview
Text (Veerman-etal-Heart-2020-Dysregulation-of-endothelial-cell-connexin-43)
Veerman_etal_Heart_2020_Dysregulation_of_endothelial_cell_connexin_43.pdf
Accepted Author Manuscript

Download (426kB)| Preview

    Abstract

    Introduction: Anthracyclines, such as doxorubicin, remain an important class of chemotherapeutic agent however their efficacy in treating cancer is limited by a cumulative dose-dependent cardiotoxicity. Whilst most studies have focused on cardiomyocyte impairment, circulating doxorubicin has been shown to impact human microvascular responses to doxorubicin in coronary vessels.1 Studies show increased endothelial cell permeability resulting in increased paracellular permeability due to damage to the integrity of cell-cell junctions.2 Strategies to maintain vessel integrity and prevent endothelial cell dysregulation could represent a novel therapeutic opportunity to limit the toxic effects of doxorubicin. The aim of this project was to assess the impact of doxorubicin upon endothelial gap junction proteins, in particular connexin-43 (Cx43).