Abstract
Daunorubicin-induced arterial stiffness in Down syndrome
Physiology (Bethesda, Md.), Vol.38(S1)
05/01/2023
DOI: 10.1152/physiol.2023.38.s1.5733537
Abstract
Children with Down syndrome have a high risk of leukemia and are at a higher risk for delayed early onset heart failure after treatment. Cardiac toxicity is more severe in female patients. Traditional risk factors for cardiovascular diseases in the general population may not be predictive of chemotherapy-induced heart failure in the Down Syndrome population. We used the Ts65Dn Down syndrome mouse model to investigate the impact of the chemotherapy agent daunorubicin on survival and arterial stiffness, a predictor of heart failure risk. We hypothesized that arterial stiffness will be increased in Ts65Dn mice treated with daunorubicin. Four-month-old Ts65Dn (n=12) and control wild-type Ts65Dn (WT Ts65Dn, n=8) mice were treated with low (2mg/kg), high (4mg/kg) dose of daunorubicin, or saline. Mice were injected twice over two weeks. Following treatment, we measured pulse wave velocity (PWV) weekly for 8 weeks using the Indus mouse Doppler flow velocity system. There was a significant decrease in PWV in mice treated with high-dose daunorubicin (p<0.001). Additionally, high-dose daunorubicin treatment resulted in a decreased survival in Ts65Dn mice (p<0.01). Overall, high-dose daunorubicin reduced PWV and survival in Ts65Dn and WT Ts65Dn mice. Daunorubicin has a dose-dependent impact on PWV in Ts65Dn and WT Ts65Dn mice. High-dose daunorubicin decreased aortic stiffness and increased mortality in Ts65Dn and WT Ts65Dn mice. This is the first demonstration that daunorubicin, the well known cardiotoxic agent, significantly impacts the conducting vasculature in Down syndrome as well. NIH R21 HD099573 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Details
- Title: Subtitle
- Daunorubicin-induced arterial stiffness in Down syndrome
- Creators
- Michelle Buckman - University of IowaAnastasiia Vasileva - University of IowaMikhail Vasilyev - University of IowaCharles Jedlicka - University of IowaHardik Kalra - University of IowaLara DeRuisseau - University of Health Sciences and PharmacyMichael Tomasson - University of IowaMelissa Bates - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Physiology (Bethesda, Md.), Vol.38(S1)
- Publisher
- American Physiological Society
- DOI
- 10.1152/physiol.2023.38.s1.5733537
- ISSN
- 1548-9213
- eISSN
- 1548-9221
- Language
- English
- Date published
- 05/01/2023
- Academic Unit
- Internal Medicine; Fraternal Order of Eagles Diabetes Research Center; Health and Human Physiology; Hematology, Oncology, and Blood & Marrow Transplantation
- Record Identifier
- 9984528090002771
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