Chemotherapy-induced acute vascular injury involves intracellular generation of ROS via activation of the acid sphingomyelinase pathway.
Acid sphingomyelinase
Cisplatin
Doxorubicin
Normal tissues
Vascular injury
Journal
Cellular signalling
ISSN: 1873-3913
Titre abrégé: Cell Signal
Pays: England
ID NLM: 8904683
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
11
12
2020
revised:
23
02
2021
accepted:
24
02
2021
pubmed:
2
3
2021
medline:
18
1
2022
entrez:
1
3
2021
Statut:
ppublish
Résumé
Several categories of chemotherapy confer substantial risk for late-term vascular morbidity and mortality. In the present study, we aimed to investigate the mechanism of acute chemotherapy-induced vascular injury in normal tissues. Specifically, we looked at activation of the acid sphingomyelinase (ASMase)/ceramide pathway, which leads to generation of reactive oxygen species (ROS) and induction of oxidative stress that may result in vascular injury. In particular, we focused on two distinct drugs, doxorubicin (DOX) and cisplatin (CIS) and their effects on normal endothelial cells. In vitro, DOX resulted in increased ASMase activity, intra-cellular ROS production and induction of apoptosis. CIS treatment generated significantly reduced effects in endothelial cells. In-vivo, murine femoral arterial blood flow was measured in real-time, during and after DOX or CIS administration, using fluorescence optical imaging system. While DOX caused constriction of small vessels and disintegration of large vessels' wall, CIS induced minor vascular changes in arterial blood flow, correlating with the in vitro findings. These results demonstrate that DOX induces acute vascular injury by increased ROS production, via activation of ASMase/ceramide pathway, while CIS increases ROS production and its immediate extracellular translocation, without causing detectable acute vascular injury. Our findings may potentially lead to the development of new strategies to prevent long-term cardiovascular morbidity in cancer survivors.
Identifiants
pubmed: 33647448
pii: S0898-6568(21)00057-7
doi: 10.1016/j.cellsig.2021.109969
pmc: PMC10402763
mid: NIHMS1819651
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Reactive Oxygen Species
0
Doxorubicin
80168379AG
Cisplatin
Q20Q21Q62J
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
109969Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA105125
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
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