The Effects of the Chemotherapeutic Agent Doxorubicin on Cardiac Fibroblast Function
Faculty Mentor Information
Dr. Xinzhu Pu
Abstract
Doxorubicin (DOX) is a highly effective chemotherapeutic used to treat many adult and pediatric cancers, such as solid tumors, leukemia, lymphomas and breast cancer. However, its use is limited due to a dose-dependent cardiotoxicity, which can lead to lethal cardiomyopathy. The toxic effects of DOX on cardiomyocytes have been studied extensively. In contrast, effects of DOX on cardiac fibroblasts (CFBs), the largest cell population in the heart, are largely unknown. In this study, CFBs isolated from mouse heart tissue were exposed to various concentrations of DOX and the cytotoxicity of DOX was determined. The collagen production of CFBs was visualized using Sirius Red staining to examine the impact of DOX on cardiac extracellular matrix (ECM), which provides structural support of the heart. The expression of a panel of genes related to ECM and cell adhesions in CFBs after DOX treatment were determined using real time polymerization chain reactions (RT-PCR). Results of these experiments could extend the current knowledge about the mechanisms of DOX-induced cardiotoxicity and possibly open new avenues for treatment.
The Effects of the Chemotherapeutic Agent Doxorubicin on Cardiac Fibroblast Function
Doxorubicin (DOX) is a highly effective chemotherapeutic used to treat many adult and pediatric cancers, such as solid tumors, leukemia, lymphomas and breast cancer. However, its use is limited due to a dose-dependent cardiotoxicity, which can lead to lethal cardiomyopathy. The toxic effects of DOX on cardiomyocytes have been studied extensively. In contrast, effects of DOX on cardiac fibroblasts (CFBs), the largest cell population in the heart, are largely unknown. In this study, CFBs isolated from mouse heart tissue were exposed to various concentrations of DOX and the cytotoxicity of DOX was determined. The collagen production of CFBs was visualized using Sirius Red staining to examine the impact of DOX on cardiac extracellular matrix (ECM), which provides structural support of the heart. The expression of a panel of genes related to ECM and cell adhesions in CFBs after DOX treatment were determined using real time polymerization chain reactions (RT-PCR). Results of these experiments could extend the current knowledge about the mechanisms of DOX-induced cardiotoxicity and possibly open new avenues for treatment.