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. 2021 Oct 29;9(11):1574. doi: 10.3390/biomedicines9111574

Table 2.

Interventions that modulate SIRT3 signaling in cardiac hypertrophy.

Experimental Model Intervention The Effect of Intervention Reference
Adult male CD-1 mice with induced cardiac fibrosis Honokiol Protects against the appearance and progression of cardiac hypertrophy by activating mitochondrial SIRT3;
Honokiol directly binds to SIRT3 and increases its enzymatic activity, affinity for NAD+ and gene expression.
[124]
Male Sprague Dawley rats; Transverse aortic constriction (TAC)-induced hypertrophy Choline Decreases cardiac hypertrophy and fibroses by activating SIRT3-AMPK-UPRmt signaling; Improves metabolic function;
Increases serum beta-hydroxy butyrate and acetylcholine levels;
Increases cardiac levels of enzymes required to metabolize ketone bodies and fatty acids that decrease cardiac hypertrophy.
[125]
TAC mice models Sesamin Decreases cardiac hypertrophy, fibrosis and inflammation;
Improves cardiac function;
Sesamin-induced reduction in hypertrophy is dependent on SIRT3, which decreases ROS; Increases SIRT3 and SOD2 expression and decreases FOXO3a phosphorylation.
[126]
In vitro neonatal rat cardiomyocytes hypertrophy model induced by ANGII Hydrogen sulfide ↑ SIRT3 promoter activity and expression;
↓ Hypertrophy, ↑ mt function, ↑ SOD2 and FOXO3a expression, ↓ oxidative stress;
All hydrogen sulfide-induced changes were SIRT3-dependent.
[127]
Mice with TAC induced hypertrophy ↓ Cardiac hypertrophy, ↓ ROS, ↓ Blood pressure;
Restores myocardial mitochondrial structure, number and volume;
↑ OPA1, MFN1, MFN2 (mitochondrial fusion genes that increase respiratory chain efficiency) and pro PGC-1α, all the modifications being SIRT3 dependent.
[127]
Mice with TAC induced hypertrophy Dihydromyricetin ↓ Hypertrophy, ↓ ROS, ↑ expression and activity of SIRT3, FOXO3a, SOD2;
Activates AMPK-PGC1alpha-ERRalpha axis, which increases SIRT3 expression and leads to mtSOD2 deacetylation and decreased oxidative damage.
[128]
[129]
Resveratrol ↓ Cardiac hypertrophy and collagen deposition,
↑ Cardiac function, all in an SIRT3-dependent manner;
In vitro, prevents fibroblast-myoblast differentiation by inhibiting TGFbeta-Smad3 signaling.
[130]
NAD+ ↓ Hypertrophy in a SIRT3-dependent manner by activating SIRT3-LKB1-AMPK signaling and culminates with decreased mTOR activity and decreased hypertrophy;
Pathologic cardiac hypertrophy decreases Nampt and NAD+ levels (but not in exercise-induced hypertrophy).
[131]
Emodin ↑ PGC-1α-SIRT3 signaling. [132]
Angiotensin II induced hypertrophy in cardiomyoblast H9c2 cells 1,25-OH vitamin D3 ↓ Hypertrophy in a SIRT3 independent manner;
SIRT3 expression was unaffected by the intervention.
[133]

Abbreviations: ↑ increases, ↓ decreases.