Developing a Reliable Mouse Model for Cancer Therapy-Induced Cardiovascular Toxicity in Cancer Patients and Survivors

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dc.citation.articleNumber26en_US
dc.citation.journalTitleFrontiers in Cardiovascular Medicineen_US
dc.citation.volumeNumber5en_US
dc.contributor.authorKo, Kyung Aeen_US
dc.contributor.authorWang, Yinen_US
dc.contributor.authorKotla, Sivareddyen_US
dc.contributor.authorFujii, Yukaen_US
dc.contributor.authorVu, Hang Thien_US
dc.contributor.authorVenkatesulu, Bhanu P.en_US
dc.contributor.authorThomas, Tamlyn N.en_US
dc.contributor.authorMedina, Jan L.en_US
dc.contributor.authorGi, Young Jinen_US
dc.contributor.authorHada, Megumien_US
dc.contributor.authorGrande-Allen, Janeen_US
dc.contributor.authorPatel, Zarana S.en_US
dc.contributor.authorMilgrom, Sarah A.en_US
dc.contributor.authorKrishnan, Sunilen_US
dc.contributor.authorFujiwara, Keigien_US
dc.contributor.authorAbe, Jun-Ichien_US
dc.date.accessioned2018-11-15T17:16:11Zen_US
dc.date.available2018-11-15T17:16:11Zen_US
dc.date.issued2018en_US
dc.description.abstractBACKGROUND: The high incidence of cardiovascular events in cancer survivors has long been noted, but the mechanistic insights of cardiovascular toxicity of cancer treatments, especially for vessel diseases, remain unclear. It is well known that atherosclerotic plaque formation begins in the area exposed to disturbed blood flow, but the relationship between cancer therapy and disturbed flow in regulating plaque formation has not been well studied. Therefore, we had two goals for this study; (1) Generate an affordable, reliable, and reproducible mouse model to recapitulate the cancer therapy-induced cardiovascular events in cancer survivors, and (2) Establish a mouse model to investigate the interplay between disturbed flow and various cancer therapies in the process of atherosclerotic plaque formation. METHODS AND RESULTS: We examined the effects of two cancer drugs and ionizing radiation (IR) on disturbed blood flow-induced plaque formation using a mouse carotid artery partial ligation (PCL) model of atherosclerosis. We found that doxorubicin and cisplatin, which are commonly used anti-cancer drugs, had no effect on plaque formation in partially ligated carotid arteries. Similarly, PCL-induced plaque formation was not affected in mice that received IR (2 Gy) and PCL surgery performed one week later. In contrast, when PCL surgery was performed 26 days after IR treatment, not only the atherosclerotic plaque formation but also the necrotic core formation was significantly enhanced. Lastly, we found a significant increase in p90RSK phosphorylation in the plaques from the IR-treated group compared to those from the non-IR treated group. CONCLUSIONS: Our results demonstrate that IR not only increases atherosclerotic events but also vulnerable plaque formation. These increases were a somewhat delayed effect of IR as they were observed in mice with PCL surgery performed 26 days, but not 10 days, after IR exposure. A proper animal model must be developed to study how to minimize the cardiovascular toxicity due to cancer treatment.en_US
dc.identifier.citationKo, Kyung Ae, Wang, Yin, Kotla, Sivareddy, et al.. "Developing a Reliable Mouse Model for Cancer Therapy-Induced Cardiovascular Toxicity in Cancer Patients and Survivors." <i>Frontiers in Cardiovascular Medicine,</i> 5, (2018) Frontiers: https://doi.org/10.3389/fcvm.2018.00026.en_US
dc.identifier.digitalfcvm-05-00026en_US
dc.identifier.doihttps://doi.org/10.3389/fcvm.2018.00026en_US
dc.identifier.urihttps://hdl.handle.net/1911/103340en_US
dc.language.isoengen_US
dc.publisherFrontiersen_US
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.subject.keywordcancer treatment-related cardiovascular toxicityen_US
dc.subject.keywordatherosclerosisen_US
dc.subject.keyworddisturbed blood flowen_US
dc.subject.keywordionizing radiationen_US
dc.subject.keywordp90RSKen_US
dc.titleDeveloping a Reliable Mouse Model for Cancer Therapy-Induced Cardiovascular Toxicity in Cancer Patients and Survivorsen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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