Adriamycin enhanced susceptibility to ischemia-reperfusion-induced hemodynamic changes and altered the expression of 52 proteins, primarily those involved in energy metabolism and the cytoskeleton.
Does adriamycin alter cardiac protein expression and hemodynamic response to ischemia-reperfusion?
Adriamycin-induced cardiotoxicity may be mediated by alterations in energy metabolism and cytoskeletal protein expression, increasing susceptibility to ischemia-reperfusion injury.
Adriamycin is a potent antitumor drug that causes severe cardiotoxicity. However, the toxic mechanisms are not clear. We used a proteomics approach to analyze changes in protein profiles after adriamycin-induced changes in hemodynamic factors. Although adriamycin itself did not affect left ventricular developed pressure (LVDP) or left ventricular end diastolic pressure (LVEDP), the drug did enhance susceptibility to ischemia-reperfusion-induced changes in LVDP, LVEDP and heart rate. Adriamycin altered the expression of 52 proteins, primarily energy metabolism and cytoskeleton proteins. Adriamycin decreased the expression of the metabolism-related proteins, ATP synthase, Sdha protein, Triose phosphate isomerase 1 (TPI-1), pyruvate dehydrogenase E1 alpha1, 6-phosphofructokinase, and fructose-1,6-bisphosphatase, as did cytoskeletal proteins, such as actin. Alterations in energy metabolism and subsequent free radical production may affect cytoskeletal protein expression, producing adriamycin-induced changes in cardiac hemodynamics.
Cui et al. (Wed,) conducted a other in Adriamycin-induced cardiotoxicity. Adriamycin was evaluated on Changes in protein profiles and hemodynamic factors. Adriamycin enhanced susceptibility to ischemia-reperfusion-induced hemodynamic changes and altered the expression of 52 proteins, primarily those involved in energy metabolism and the cytoskeleton.