Increased Afterload Augments Sunitinib-Induced Cardiotoxicity in an Engineered Cardiac Microtissue Model
Year: 2018
Type: article
Abstract: Sunitinib, a multitargeted oral tyrosine kinase inhibitor, used widely to treat solid tumors, results in hypertension in up to 47% and left ventricular dysfunction in up to 19% of treated individuals. The relative contribution of afterload toward inducing cardiac dysfunction with sunitinib treatment remains unknown. We created a preclinical model of sunitinib cardiotoxicity using engineered microtissues that exhibited cardiomyocyte death, decreases in force generation, and spontaneous beating at clinically relevant doses. Simulated increases in afterload augmented sunitinib cardiotoxicity in both rat and human microtissues, which suggest that antihypertensive therapy may be a strategy to prevent left ventricular dysfunction in patients treated with sunitinib.
Institution: University of Pennsylvania
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,750
Funders: National Science Foundation, American Heart Association, Pfizer, University of Pennsylvania, Institute for Translational Medicine and Therapeutics, National Institutes of Health, Perelman School of Medicine, University of Pennsylvania, National Heart, Lung, and Blood Institute, National Center for Research Resources, National Center for Advancing Translational Sciences
OpenAlex ID: W2801312657