Many chemotherapeutics (including anthracyclines, such as doxorubicin) induce the proapoptotic transcription factor p53 in the tumor and nonspecifically in the heart, promoting heart failure.
Activation of p53-dependent apoptosis is critical for tumor suppression but aberrant activation of p53 also leads to developmental defects and heart failure.
Wnt/β-catenin signaling and the p53 pathway, both of which are key regulators of aging, have been demonstrated to play a critical role in the pathogenesis of heart failure.
We observed that EAT expressed more p53 mRNA than SAT (1.73 ± 0.07 vs. 1.69 ± 0.04, P < 0.001) and its levels were higher in HF patients (1.75 ± 0.07 vs. 1.70 ± 0.04, P < 0.01 in EAT and 1.70 ± 0.04 vs. 1.67 ± 0.04, P < 0.05 in SAT).
Our data provide evidence, for the first time, that the coherence of p53 with myo plays an active role during the transition of CH to HF in a model of HF induced by myo overexpression.
CaMKIIdelta plays a critical role in the development of heart failure in part by accumulation of p53 and induction of cardiomyocyte apoptosis in the DCM mouse model.
Tumor suppressor protein p53 accumulates in the myocardium after myocardial infarction, causes apoptosis of cardiomyocytes, and plays an important role in the progression into heart failure.