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Review
. 2011 Jan;21(1):27-32.
doi: 10.1016/j.tcm.2012.01.005.

Protection of the heart against ischemia/reperfusion by silent information regulator 1

Takanobu Yamamoto  1 , Junichi Sadoshima
Affiliations
Review

Protection of the heart against ischemia/reperfusion by silent information regulator 1

Takanobu Yamamoto et al. Trends Cardiovasc Med. 2011 Jan.

Abstract

Myocardial ischemia followed by ischemia/reperfusion (I/R) induces irreversible damage to cardiac muscle. Medical treatment that effectively prevents I/R injury would alleviate the consequent development of cardiac remodeling and failure. Mechanisms that extend life span often make organisms resistant to stress, and an accumulation of such mechanisms may prevent aging and susceptibility to age-associated diseases. Sirtuins are a group of molecules involved in longevity and stress resistance. Stimulation of silent information regulator 1 (Sirt1), the mammalian ortholog of yeast Sir2 and a member of the sirtuin family, extends the life span of mice fed a high-fat diet and retards aging in the heart. Recent evidence suggests that stimulation of Sirt1 mimics ischemic preconditioning and protects the heart from I/R injury, suggesting an intriguing possibility of using longevity factors to treat cardiac disease. Here, we discuss the cardioprotective effects of Sirt1 and possible underlying mechanisms.

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Figures

Figure 1
Figure 1. Cardioprotective Effects of Sirt1 on Ischemia/Reperfusion. Expression and activity of Sirt1 are regulated by multiple mechanisms
Sirt1 protects the heart from I/R injury through multiple mechanisms. For example, Sirt1 suppresses ROS production, apoptosis and inflammation, whereas it also induces autophagy. The effect of Sirt1 is mediated through both protein deacetylation (post-translational modification) and transcription (such as modulation of FoxO). ROS: reactive oxygen species; UPR: unfolded protein response; NF-κB: nuclear factor of κ light polypeptide gene enhancer in B-cells; XBP: X-box binding protein; Bcl-xL: B cell lymphoma like X; Bax: Bcl-2-associated X; MnSOD: manganese superoxide dismutase; Trx: thioredoxin; Rab7: Rab-protein 7; LC3-II: light chain 3-II; FoxO1: forkhead box O1; NAD: nicotinamide adenine dinucleotide; STACs: Sirt1-activating compounds.
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