Abstract
Post-daunorubicin treatment effects on cardiovascular function in the Ts65Dn mouse model of Down syndrome
Physiology (Bethesda, Md.), Vol.41(S1), 2293068
05/2026
DOI: 10.1152/physiol.2026.41.S1.2293068
Abstract
Abstract only Adults with Down syndrome (DS) are two times more likely to be diagnosed with chronic heart failure post-anthracycline chemotherapy compared to age and sex-matched individuals without DS. They have an elevated lifetime risk of cardiovascular diseases, increasing their likelihood of anthracycline-induced chronic cardiovascular toxicity. We investigated the chronic effects of daunorubicin on the cardiovascular system of the adult Ts65Dn mouse model of DS compared to wild-type euploid mice (WT). WT and Ts65Dn mice received two doses of 2mg/kg or 4mg/kg of daunorubicin or saline and were monitored for up to 117 days. Cardiac and vascular function were evaluated using left ventricular catheterization, histology, pulse wave velocity, and cardiac troponin I tests. Survival significantly decreased in the Ts65Dn 4mg/kg group compared to saline controls (p< 0.001). Further experiments were carried out with the saline and 2mg/kg groups, which exhibited lower mortality. Body weight (p=0.001), end-diastolic pressure (p=0.016), and left ventricular mass (p=0.021) decreased in treated mice. The effect of treatment differed significantly between strains for ejection fraction and cardiac fibrosis (p=0.029 and p=0.001). Pulse wave velocity increased over time (p< 0.001). Treatment had significantly different effects on collagen in the thoracic aorta across strains (p=0.002). There was a strain difference for cardiac troponin I, indicating an increase in Ts65Dn mice (p=0.020). Daunorubicin altered cardiac function and led to a distinct cardiovascular remodeling phenotype in Ts65Dn mice. More mechanistic studies are warranted to outline the pathophysiology of anthracycline cardiovascular toxicity in DS. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Details
- Title: Subtitle
- Post-daunorubicin treatment effects on cardiovascular function in the Ts65Dn mouse model of Down syndrome
- Creators
- Michelle Buckman - University of IowaAnastasiia Vasileva - University of IowaHardik Kalra - University of IowaImmaculate Edwin - University of IowaGuiru Ma - University of IowaMikhail Vasilyev - University of IowaBarry London - University of IowaCharles Jedlicka - University of IowaGary Beasley - University of IowaPatrick Breheny - University of IowaMichael Tomasson - University of IowaMelissa Bates - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Physiology (Bethesda, Md.), Vol.41(S1), 2293068
- DOI
- 10.1152/physiol.2026.41.S1.2293068
- ISSN
- 1548-9213
- eISSN
- 1548-9221
- Publisher
- American Physiology
- Language
- English
- Date published
- 05/2026
- Academic Unit
- Molecular Physiology and Biophysics; Cardiology; Hematology, Oncology, and Blood & Marrow Transplantation; Stead Family Department of Pediatrics; Biostatistics; Cardiovascular Medicine; Health, Sport, and Human Physiology ; Internal Medicine
- Record Identifier
- 9985163700502771
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