Redox Homeostasis in Cardiovascular Disease: The Role of Mitochondrial Sirtuins

Zullo, Alberto; Guida, Rosa; Sciarrillo, Rosaria; Mancini, Francesco Paolo

doi:10.3389/fendo.2022.858330

Cited by 19 publications

(13 citation statements)

References 76 publications

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“… 183 Localized in the mitochondria, SIRT4 regulates proteins involved in metabolic reactions, antioxidant pathways and autophagy, thus maintaining mitochondrial homeostasis. 307 Overexpression of SIRT4 inhibits ROS production and autophagy by activating the Akt/mTOR signaling pathway. 308 Furthermore, the SIRT4/optic atrophy 1 axis is causally linked to mitochondrial dysfunction and altered mitochondrial dynamics that translates into aging-associated decreased mitophagy.…”

Section: Introductionmentioning

confidence: 99%

The sirtuin family in health and disease

Zhang

Chen

et al. 2022

Sig Transduct Target Ther

223

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Sirtuins (SIRTs) are nicotine adenine dinucleotide(+)-dependent histone deacetylases regulating critical signaling pathways in prokaryotes and eukaryotes, and are involved in numerous biological processes. Currently, seven mammalian homologs of yeast Sir2 named SIRT1 to SIRT7 have been identified. Increasing evidence has suggested the vital roles of seven members of the SIRT family in health and disease conditions. Notably, this protein family plays a variety of important roles in cellular biology such as inflammation, metabolism, oxidative stress, and apoptosis, etc., thus, it is considered a potential therapeutic target for different kinds of pathologies including cancer, cardiovascular disease, respiratory disease, and other conditions. Moreover, identification of SIRT modulators and exploring the functions of these different modulators have prompted increased efforts to discover new small molecules, which can modify SIRT activity. Furthermore, several randomized controlled trials have indicated that different interventions might affect the expression of SIRT protein in human samples, and supplementation of SIRT modulators might have diverse impact on physiological function in different participants. In this review, we introduce the history and structure of the SIRT protein family, discuss the molecular mechanisms and biological functions of seven members of the SIRT protein family, elaborate on the regulatory roles of SIRTs in human disease, summarize SIRT inhibitors and activators, and review related clinical studies.

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Section: Introductionmentioning

confidence: 99%

The sirtuin family in health and disease

Zhang

Chen

et al. 2022

Sig Transduct Target Ther

223

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“…SIRT4 and SIRT5 are two other mitochondrial sirtuins, which have been reported to be regulators of cellular metabolism ( 87 ). For instance, mitochondrial SIRT3, 4 and 5 may affect cell metabolism and ROS homeostasis, ultimately regulating cardiovascular health ( 88 ). Interestingly, on the one hand, SIRT4 could attenuate inflammatory damage to human umbilical vein endothelial cells ( 89 , 90 ).…”

Section: Discussionmentioning

confidence: 99%

The Role of Sirtuins in Osteogenic Differentiation of Vascular Smooth Muscle Cells and Vascular Calcification

Wang

2022

Front. Cardiovasc. Med.

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Vascular calcification (VC) is a common pathological change in many chronic diseases, such as diabetes and chronic kidney disease. It is mainly deposited in the intima and media of vessels in the form of hydroxyapatite. Recently, a lot of research has been performed to show that VC is associated with various cellular stresses, such as hyperphosphate, hyperglycemia and oxidative stress. Unfortunately, our understanding of the pathogenesis of calcification is far from comprehensive. Sirtuins belong to a family of class III highly conserved deacetylases that are involved in the regulation of biological and cellular processes including mitochondrial biogenesis, metabolism, oxidative stress, inflammatory response, DNA repair, etc. Numerous studies have shown that sirtuins might play protective roles in VC, and restoring the activity of sirtuins may be a potentially effective treatment for VC. However, the exact mechanism of their vascular protection remains unclear. Here, we reviewed the roles of sirtuins in the osteogenic transformation of vascular smooth muscle cells and the development of VC. We also elucidated the applications of sirtuins agonists for the treatment of VC.

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“…Administration of atorvastatin increased the expression of SIRT1, but no change was observed in the rosuvastatin group [ 82 ]. SIRT3 deficiency causes cellular dysfunction and is related to the development of various diseases, including metabolic disorders, aging, and CVD [ 96 ]. The sirtuin members also may have negative effects on CVDs.…”

Section: Evidence For Statins In the Regulation Of Sirtuin-mediated A...mentioning

confidence: 99%

Regulatory Effects of Statins on SIRT1 and Other Sirtuins in Cardiovascular Diseases

Khayatan

Razavi

Arab

et al. 2022

Life

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Adverse cardiovascular disease (CVD) outcomes, such as sudden cardiac death, acute myocardial infarction, and stroke, are often catastrophic. Statins are frequently used to attenuate the risk of CVD-associated morbidity and mortality through their impact on lipids and they may also have anti-inflammatory and other plaque-stabilization effects via different signaling pathways. Different statins, including atorvastatin, rosuvastatin, pravastatin, pitavastatin, and simvastatin, are administered to manage circulatory lipid levels. In addition, statins are potent inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase via modulating sirtuins (SIRTs). During the last two decades, SIRTs have been investigated in mammals and categorized as a family of nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylases (HDACs) with significant oxidative stress regulatory function in cells—a key factor in extending cell lifespan. Recent work has demonstrated that statins upregulate SIRT1 and SIRT2 and downregulate SIRT6 in both in vitro and in vivo experiments and clinical trials. As statins show modulatory properties, especially in CVDs, future investigations are needed to delineate the role of SIRT family members in disease and to expand knowledge about the effects of statins on SIRTs. Here, we review what is currently known about the impact of statins on SIRTs and how these changes correlate with disease, particularly CVDs.

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Redox Homeostasis in Cardiovascular Disease: The Role of Mitochondrial Sirtuins

Cited by 19 publications

References 76 publications

The sirtuin family in health and disease

The sirtuin family in health and disease

The Role of Sirtuins in Osteogenic Differentiation of Vascular Smooth Muscle Cells and Vascular Calcification

Regulatory Effects of Statins on SIRT1 and Other Sirtuins in Cardiovascular Diseases

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