What question did this study set out to answer?

To determine the role and molecular mechanism of SIRT2 in aging-related and angiotensin II–induced pathological cardiac hypertrophy.

September 25, 2017Circulation

SIRT2 Acts as a Cardioprotective Deacetylase in Pathological Cardiac Hypertrophy

Q: What is the clinical evidence from this study?

Population: Pathological cardiac hypertrophy. Intervention: SIRT2 knockout and overexpression vs. Wild-type littermates. Primary outcome: Cardiac hypertrophy, fibrosis, and cardiac function.

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Key result

SIRT2 overexpression protected against Ang II-induced cardiac hypertrophy and fibrosis and rescued cardiac function in mice by promoting AMPK activation via LKB1 deacetylation.

Why the study?

Does SIRT2 modulate aging-related and Ang II-induced pathological cardiac hypertrophy in mice?

Key Points

To determine the role and molecular mechanism of SIRT2 in aging-related and angiotensin II–induced pathological cardiac hypertrophy.
Assessed aging-associated cardiac remodeling in 24-month-old male C57BL/6J wild-type and Sirt2 knockout mice.
Infused 8- to 12-week-old Sirt2 knockout, cardiac-specific SIRT2 transgenic (SIRT2-Tg), and control littermate mice with angiotensin II (1.3 mg/kg/d) for 4 weeks.
Treated angiotensin II–infused wild-type and Sirt2 knockout mice with metformin (200 mg/kg/d) while analyzing cardiac hypertrophy, fibrosis, ejection fraction, and molecular signaling via LKB1 and AMPK.
SIRT2 expression declined in hypertrophic mouse hearts, while Sirt2 knockout worsened cardiac hypertrophy and fibrosis and impaired ejection fraction and fractional shortening in aged and angiotensin II–infused mice.
Cardiac-specific overexpression of SIRT2 protected against angiotensin II–induced hypertrophy and fibrosis while restoring cardiac function.
Mechanistically, SIRT2 bound and deacetylated LKB1 at lysine 48 to promote LKB1-AMPK pathway activation; knockout of Sirt2 blunted AMPK activation and abolished the cardioprotective benefits of metformin.

Structured PICO

Does SIRT2 modulate aging-related and Ang II-induced pathological cardiac hypertrophy in mice?

Population

Male C57BL/6J wild-type, Sirt2 knockout, and SIRT2-Tg mice subjected to aging-related and Ang II-induced cardiac hypertrophy.

Intervention

Sirt2 knockout, cardiac-specific SIRT2 overexpression, and metformin (200 mg/kg/d) treatment in Ang II-infused mice (1.3 mg/kg/d for 4 weeks).

Comparator

Wild-type littermates and vehicle-treated controls.

Outcome

Cardiac hypertrophy, fibrosis, and cardiac function (ejection fraction and fractional shortening).surrogate

SIRT2 acts as a cardioprotective deacetylase that promotes AMPK activation by deacetylating LKB1, protecting against aging- and stress-induced cardiac hypertrophy.

Discussion

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Implication

SIRT2 may modulate hypertrophy in mice; leaves open therapeutic relevance for human heart failure.

Cite This Study

Tang et al. (2017) studied Pathological cardiac hypertrophy. SIRT2 knockout and overexpression vs. Wild-type littermates was evaluated on Cardiac hypertrophy, fibrosis, and cardiac function. SIRT2 overexpression protected against Ang II-induced cardiac hypertrophy and fibrosis and rescued cardiac function in mice by promoting AMPK activation via LKB1 deacetylation.

synapsesocial.com/papers/6a97c0c244220fce7874bb3e https://doi.org/10.1161/circulationaha.117.028728

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SIRT2 Acts as a Cardioprotective Deacetylase in Pathological Cardiac Hypertrophy

Key Points

Structured PICO

Discussion

Implication

Cite This Study

SIRT2 Acts as a Cardioprotective Deacetylase in Pathological Cardiac Hypertrophy

Key Points

Structured PICO

Discussion

Implication

Cite This Study

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