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May 1, 2022Circulation Heart FailureOpen Access

Mitochondrial Sirtuin-3 (SIRT3) Prevents Doxorubicin-Induced Dilated Cardiomyopathy by Modulating Protein Acetylation and Oxidative Stress

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Key result

Increased M1-SIRT3 expression prevented doxorubicin-induced cardiac remodeling and dysfunction in transgenic mice and attenuated superoxide formation in cardiomyocytes.

Why the study?

High doses of doxorubicin put cancer patients at risk for dilated cardiomyopathy, and whether SIRT3 expression can attenuate this toxicity in vivo by preventing mitochondrial protein acetylation was investigated.

Population

Nontransgenic, M3-SIRT3, and M1-SIRT3 transgenic mice, and primary rat and human induced stem cell derived cardiomyocytes

Comparison

M3-SIRT3 or M1-SIRT3 expression vs controls during doxorubicin treatment

Design

Preclinical animal and cellular study

Follow-up

4 weeks

Discussion

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Member takes

Overview

SIRT3 overexpression should not yet guide cardio-oncology practice; leaves open its role as a target against anthracycline cardiomyopathy.

Structured PICO

P
Population
Transgenic mice and primary rat and human induced stem cell-derived cardiomyocytes treated with doxorubicin to assess the protective effects of SIRT3.
I
Intervention
M1-SIRT3 or M3-SIRT3 overexpression during doxorubicin treatment (8 mg/kg body weight per week for 4 weeks in vivo).
C
Comparator
Nontransgenic mice or non-transduced cells treated with doxorubicin; saline-treated controls.
O
Outcome
Cardiac structure and function assessed by echocardiography, and mitochondrial protein acetylation.surrogate

Mitochondrial-localized SIRT3 (M1-SIRT3) prevents doxorubicin-induced dilated cardiomyopathy and oxidative stress in preclinical models, highlighting a potential therapeutic target.

Cite This Study

A 2022 study studied Doxorubicin-induced dilated cardiomyopathy. SIRT3 expression (M1-SIRT3 and M3-SIRT3) vs. Nontransgenic mice and deacetylase deficient mutants was evaluated on Cardiac structure and function and oxidative stress. Increased M1-SIRT3 expression prevented doxorubicin-induced cardiac remodeling and dysfunction in transgenic mice and attenuated superoxide formation in cardiomyocytes.

synapsesocial.com/papers/6a7f3750dac4de2d60b3ade2https://doi.org/10.1161/circheartfailure.121.008547
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1The role of sirtuins in mitochondrial function and doxorubicin-induced cardiac dysfunction2017 · 39 citations
  2. 2Honokiol, an activator of Sirtuin-3 (SIRT3) preserves mitochondria and protects the heart from doxorubicin-induced cardiomyopathy in mice2017 · 195 citations
  3. 3Mitochondrial Deacetylase Sirt3 Reduces Vascular Dysfunction and Hypertension While Sirt3 Depletion in Essential Hypertension Is Linked to Vascular Inflammation and Oxidative Stress2019 · 380 citations
  4. 4Renal mitochondrial oxidative stress is enhanced by the reduction of Sirt3 activity, in Zucker diabetic fatty rats2018 · 54 citations
  5. 5SIRT3 Protein Deacetylates Isocitrate Dehydrogenase 2 (IDH2) and Regulates Mitochondrial Redox Status2012 · 451 citations