Abstract Title

Effects of Doxorubicin on Cardiac Fibroblasts and the Extracellular Matrix

Additional Funding Sources

This project is supported by a 2020-2021 STEM Undergraduate Research Grant from the Higher Education Research Council, Institutional Development Awards (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under Grant Nos. P20GM103408 and P20GM109095, and National Science Foundation S-STEM Gateway Scholarships in Biological Sciences under Grant Award No. DUE-1644233. We also acknowledge support from the Biomolecular Research Center at Boise State with funding from the National Science Foundation, Grant Nos. 0619793 and 0923535, the M.J. Murdock Charitable Trust, and the Idaho State Board of Education.

Abstract

Cardiotoxicity has been associated with various types of chemotherapeutic drugs contributing to a plethora of cardiac insults and is a significant side effect when treating cancer. Many highly effective anticancer drugs are severely dose dependent, and at higher doses can lead to: cardiac arrhythmias, hypertension, and lethal cardiomyopathy. A well known example of this cardiotoxic side effect is Doxorubicin, a common chemotherapeutic used to treat cancers of the breast, ovary, bladder, and thyroid. Extensive research has shown that high doses of doxorubicin detrimentally alters the normal function of cardiac fibroblasts and cardiomyocytes. In contrast to the extensive research on the toxic effects of chemotherapeutics like doxorubicin in cardiomyocytes, little is known on the effects in cardiac fibroblasts and mechanisms of these drugs on the cardiac extracellular matrix (cECM). We show that doxorubicin has a direct impact on cardiac fibroblasts and in turn the function of the cECM, indicating that the cECM plays an important role in cardiac toxicity induced by doxorubicin.

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Effects of Doxorubicin on Cardiac Fibroblasts and the Extracellular Matrix

Cardiotoxicity has been associated with various types of chemotherapeutic drugs contributing to a plethora of cardiac insults and is a significant side effect when treating cancer. Many highly effective anticancer drugs are severely dose dependent, and at higher doses can lead to: cardiac arrhythmias, hypertension, and lethal cardiomyopathy. A well known example of this cardiotoxic side effect is Doxorubicin, a common chemotherapeutic used to treat cancers of the breast, ovary, bladder, and thyroid. Extensive research has shown that high doses of doxorubicin detrimentally alters the normal function of cardiac fibroblasts and cardiomyocytes. In contrast to the extensive research on the toxic effects of chemotherapeutics like doxorubicin in cardiomyocytes, little is known on the effects in cardiac fibroblasts and mechanisms of these drugs on the cardiac extracellular matrix (cECM). We show that doxorubicin has a direct impact on cardiac fibroblasts and in turn the function of the cECM, indicating that the cECM plays an important role in cardiac toxicity induced by doxorubicin.