Publication
Title
Doxorubicin induces arterial stiffness : a comprehensive in vivo and ex vivo evaluation of vascular toxicity in mice
Author
Abstract
Arterial stiffness is an important predictor of cardiovascular risk. Clinical studies have demonstrated that arterial stiffness increases in cancer patients treated with the chemotherapeutic doxorubicin (DOX). However, the mechanisms of DOX-induced arterial stiffness remain largely unknown. This study aimed to evaluate artery stiffening in DOX-treated mice using in vivo and ex vivo techniques. Male C57BL/6J mice were treated for 2 weeks with 2 mg/kg (low dose) or 4 mg/kg (high dose) of DOX weekly. Arterial stiffness was assessed in vivo with ultrasound imaging (abdominal aorta pulse wave velocity (aaPWV)) and applanation tonometry (carotid-femoral PWV) combined with ex vivo vascular stiffness and reactivity evaluation. The high dose increased aaPWV, while cfPWV did not reach statistical significance. Phenylephrine (PE)-contracted aortic segments showed a higher Peterson’s modulus (Ep) in the high dose group, while Ep did not differ when vascular smooth muscle cells (VSMCs) were relaxed by a NO donor (DEANO). In addition, aortic rings of DOX-treated mice showed increased PE contraction, decreased basal nitric oxide (NO) index and impaired acetylcholine-induced endothelium-dependent relaxation. DOX treatment contributed to endothelial cell loss and reduced endothelial nitric oxide synthase (eNOS) expression in the aorta. In conclusion, we have replicated DOX-induced arterial stiffness in a murine model and this aortic stiffness is driven by impaired endothelial function, contributing to increased vascular tone.
Language
English
Source (journal)
Toxicology letters. - Amsterdam
Publication
Amsterdam : 2021
ISSN
0378-4274
DOI
10.1016/J.TOXLET.2021.04.015
Volume/pages
346 (2021) , p. 23-33
ISI
000649284200004
Pubmed ID
33895255
Full text (Publisher's DOI)
Full text (open access)
Full text (publisher's version - intranet only)
UAntwerpen
Faculty/Department
Research group
Project info
The investigation of arterial stiffness as a potential marker in cardio-oncology.
The pathophysiological role of physical exercise in the development of (left ventricular) myocardial fibrosis during viral myocarditis.
From hit to lead: inducing basal autophagy for treating cardiovascular diseases.
MicroRNA in heart failure: Exercise as a tool to discover candidate microRNA for therapy and personalized medicine.
Is arterial stiffness an overlooked marker in cardio-oncology?
INnovation in Safety Pharmacology for Integrated cardiovascular safety assessment to REduce adverse events and late stage drug attrition (INSPIRE).
Infla-Med: Fundamental and translational research into targets for the treatment of inflammatory diseases.
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identifier
Creation 17.05.2021
Last edited 02.10.2024
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