Activators of Sirtuin-1 and their Involvement in Cardioprotection

Abstract

SIRT1 is a nicotinamide adenosine dinucleotide (NAD+)-dependent deacetylase, which removes acetyl groups from many target proteins, such as histone proteins, transcription factors and cofactors. SIRT1-catalyzed deacetylation of these factors modulates the activity of downstream proteins, thus influencing many biological processes. SIRT1 is involved in the regulation of metabolism, inflammation, and tumor growth. The activity of this enzyme is related to the beneficial health effects of calorie restriction, such as lifespan extension and, in particular, the activation of SIRT1 has a positive impact on the cardiovascular system. Therefore, SIRT1 is considered as an attractive drug target and modulation of SIRT1 may represents a new therapeutic strategy against cardiovascular diseases, as small molecules able to activate SIRT1 can be considered as cardioprotective agents. In this review, we summarize both natural or synthetic compounds developed as SIRT1 activators, with a focus on their promising therapeutic applications in cardiovascular pathologies.

Aβ-Induced Damage Memory in hCMEC/D3 Cell Mediated by Sirtuin-1

“…The sirt-1 activator SRT2104, similar to other sirt-1 activators, increased mitochondrial content and suppressed the inflammation pathways [32]. It also exhibits endothelial protective effects which is observed in this study [32].…”

“…When the PTP opens, the contact between the cytosolic and the mitochondrial pools of pyridine nucleotides may reduce NAD + via enzymatic reactions [25]. The sirt-1 activator SRT2104, similar to other sirt-1 activators, increased mitochondrial content and suppressed the inflammation pathways [32]. It also exhibits endothelial protective effects which is observed in this study [32].…”

Cardioprotection stimulated by resveratrol and grape products prevents lethal cardiac arrhythmias in an animal model of ischemia and reperfusion

“…In red wine, the concentration of resveratrol varies from 0.09 to 18 mg/L (average of 5 mg/L) 9 . The resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a small molecule with a molecular weight of 228.246 g/mol with anti-inflammatory, antioxidant, hypoglycemic and antihypertensive and cardioprotective effects, which acts through multiple mechanisms of action, including the activation of the silent information regulator factor 2-related enzyme 1 (Sirt1), a nicotinamide adenine dinucleotide-dependent deacetylase involved in many physiological functions like oxidative stress [9][10][11][12][13][14] . Based on our recent studies, we have suggested that the combined molecular actions of resveratrol on Sirt1 and other cellular proteins involved in the regulation of functions of cardiac cells stimulates the cardioprotective response, attenuating or preventing the cytosolic and mitochondrial Ca 2+ overload and bioenergetic collapse involved in cardiac arrhythmias caused by ischemia and reperfusion in cardiac cells 3 .…”

A Systematic Review on the Role of SIRT1 in Duchenne Muscular Dystrophy

“…Due to its role in the physiological processes, SIRT1 plays a key role in various diseases, such as diabetes, obesity, cancer, neurodegenerative and cardiovascular diseases, and age-related pathologies [19].…”