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- W2955521775 abstract "Doxorubicin (DOX) is an effective anthracycline chemotherapy agent associated with several adverse side effects including cardiotoxicity. Although the mechanism responsible for the cardiotoxic effects of DOX has yet to be fully elucidated, the leading theory is that the generation of reactive oxygen species (ROS) damages cardiomyocytes and leads to cell death. ROS play a role in the expression and activation of matrix metalloproteinases (MMPs), a family of enzymes involved in extracellular matrix (ECM) degradation. Normally, MMP activity is regulated by tissue inhibitors of metalloproteinases (TIMPs). We hypothesized that DOX treatment would lead to overexpression of MMPs or underexpression of TIMPs, which would compromise the integrity of the myocardial ECM and disrupt cardiac function. PURPOSE: To investigate the effects of DOX on MMP-2, MMP-9, and TIMP-2 expression in rat cardiac tissue. METHODS: At 20 weeks of age, Sprague Dawley rats received a bolus injection of DOX (12 mg/kg; n=6) or saline (0.9%; n=8) as a control. Five days post-injection, cardiac tissue was collected from each animal, homogenized, and standardized for protein content. Samples were analyzed for expression of MMP-2, MMP-9, and TIMP-2 using western blotting with enhanced chemiluminescence. All results were normalized to GAPDH. Data were analyzed using a Student’s T-Test (α=0.05). RESULTS: Results showed significantly lower expression of MMP-9 in cardiac tissue from animals treated with DOX relative to the control (p = 0.0068). There was no significant difference in expression of MMP-2 (p = 0.8757) or TIMP-2 (p = 0.2266) between groups. CONCLUSIONS: These findings suggest that treatment with DOX significantly reduced the expression of MMP-9, contradicting our hypothesis. A potential explanation for these findings is that there is an intermediate factor affecting MMP-9 expression. Future studies should profile all components of MMP/TIMP signaling during DOX treatment." @default.
- W2955521775 created "2019-07-12" @default.
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- W2955521775 date "2019-06-01" @default.
- W2955521775 modified "2023-10-17" @default.
- W2955521775 title "The Effect Of Doxorubicin On Myocardial Extracellular Matrix Degradation" @default.
- W2955521775 doi "https://doi.org/10.1249/01.mss.0000561241.28667.8c" @default.
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