May 8, 2014Cardiovascular ResearchOpen Access

P53 inhibition exacerbates late-stage anthracycline cardiotoxicity

View Full Paper

Ask AI

Bookmark

Why the study?

Does p53 inhibition alter acute and late-stage doxorubicin-induced cardiotoxicity in a juvenile mouse model?

Population

Juvenile mice

Comparison

Doxorubicin 25 mg/kg cumulative dose vs Saline injections

Design

Preclinical

Follow-up

13 weeks after final DOX injection

Authors

WZWuqiang ZhuWinnMed WZWenjun ZhangBerkeley College WSWeinian ShouPediatric / Congenital Cardiology

Discussion

Member takes

Implication

p53 inhibition warrants caution in juvenile doxorubicin models due to late worsening; leaves open optimal timing for p53 modulation in cardiotoxicity.

Structured PICO

Does p53 inhibition alter acute and late-stage doxorubicin-induced cardiotoxicity in a juvenile mouse model?

Population

Juvenile mice (2-week-old MHC-CB7 mice expressing dominant-interfering p53 in cardiomyocytes, n=72, and non-transgenic littermates, n=70; STAT3-CKO mice with cardiac-restricted STAT3 deletion, n=16, and wild-type controls, n=17)

Intervention

Doxorubicin (DOX) 25 mg/kg cumulative dose (5 weekly intraperitoneal injections of 5 mg/kg)

Comparator

Saline injections

Outcome

Cardiac function (fractional shortening and ejection fraction) and cardiomyocyte apoptosis at acute (1 week post-treatment) and late (13 weeks post-treatment) stagessurrogate

Inhibition of p53 protects against acute doxorubicin cardiotoxicity but paradoxically exacerbates late-stage heart failure, highlighting the complex temporal role of p53 in anthracycline-induced myocardial stress.

Limitations

Direct proof of the proposed mechanism requires additional transgenic animals with conditional expression of relevant proteins

Cite This Study

Zhu et al. (2014) studied this question.

synapsesocial.com/papers/6a766b0fee08d608e595c412 https://doi.org/10.1093/cvr/cvu118

Topics

Heart failure HFrEF treatment

View Full Paper

Ask AI

Bookmark

Implication

p53 inhibition warrants caution in juvenile doxorubicin models due to late worsening; leaves open optimal timing for p53 modulation in cardiotoxicity.

P53 inhibition exacerbates late-stage anthracycline cardiotoxicity

Discussion

Member takes

Implication

Structured PICO

Limitations

Cite This Study

Topics

P53 inhibition exacerbates late-stage anthracycline cardiotoxicity

Discussion

Member takes

Implication

Structured PICO

Limitations

Cite This Study

Also Consider

Topics

Also Consider