Research Topic

Drugs Associated with Changes in Sirtuin-1 Plasma Concentration and Vascular Protection against Atherosclerosis Process: from Bench to Clinical Trials

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About this Research Topic

Sirtuins are a class of proteins that regulate a variety of cellular functions associated with longevity, such as genome integrity and cellular metabolism. Although sirtuins are associated with vascular protection in some animal species, their effects on humans are poorly understood. There are seven human sirtuins (SIRT1-7) that can be found in different subcellular locations including the cytoplasm (SIRT1, SIRT2), nucleus (SIRT1, SIRT2, SIRT6, SIRT7) and mitochondria (SIRT3, SIRT4, SIRT5). Studies in various animal species have shown an association between higher gene expression of sirtuins with longevity and lower incidence of age-related diseases such as cardiovascular, neurological and cancer.

Atherosclerosis is an immunoinflammatory process that results from a complex association of oxidized low density lipoproteins (LDLox), activated endothelial cells, monocyte-derived macrophages, T cells, and the vessel wall. Endothelial injury facilitates the entry of LDLox into the intima layer, stimulating the migration of inflammatory cells into the vessel wall and the production of inflammatory cytokines, intensifying the atherosclerotic lesion. Studies have shown that Sirt1 activation in particular, protects endothelial cells from senescence, vascular cells against DNA damage and medial degeneration for example. It is thought that Sirt1 exerts its athero-protective effects on the vessel wall by activating eNOS or by reducing cytokines activity in endothelial cells and macrophages.

SIRT1 is the most studied sirtuin due to the wide variety of protective effects on the vessel wall and its involvement in several cellular metabolic pathways. As examples, increased SIRT1 can influence various metabolic pathways that favour gluconeogenesis, reduce glycolysis and increase fatty acid oxidation. This can be in response to nutritional stimuli, particularly during calorie restriction and with phenolic compounds, and by regulating of essential metabolites such as glucose, cholesterol and fatty acids. As such, this places this protein in a central position as a universal molecular regulator that is likely to play a critical role in the systemic regulation of mammalian vascular protection.

However, further studies clarifying the mechanisms of action of Sirt1 on vascular protection are needed. Likewise, the development of new drugs may improve the pharmacological armamentarium against atherosclerotic disease. Therefore, this Research Topic aims to bring the most recent discovery on the Sirt1 mechanisms involved in vascular protection, novel pharmacological molecules that target Sirt1 for the treatment of the atherosclerosis, and animal and clinical studies related to the effects of Sirt1 against atherosclerosis.

The development of new molecules that act on Sirt1 levels can have a significant impact on reducing chronic diseases. Therefore, the proposed Research Topic on Sirt1 may be of great interest to researchers in the field of chronic degenerative diseases and also of great impact to the section of "Cardiovascular and Smooth Muscle Pharmacology" of the journal Frontiers in Pharmacology.

The intention of this Research Topic is to receive manuscripts from bench to clinical studies of interventions associated with changes in Sirt1 levels and their pathophysiological importance in the atherosclerosis process.


Keywords: Atherosclerosis, Sirtuin1, lipid metabolism, glucose metabolism disorders, animal research, clinical research


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Sirtuins are a class of proteins that regulate a variety of cellular functions associated with longevity, such as genome integrity and cellular metabolism. Although sirtuins are associated with vascular protection in some animal species, their effects on humans are poorly understood. There are seven human sirtuins (SIRT1-7) that can be found in different subcellular locations including the cytoplasm (SIRT1, SIRT2), nucleus (SIRT1, SIRT2, SIRT6, SIRT7) and mitochondria (SIRT3, SIRT4, SIRT5). Studies in various animal species have shown an association between higher gene expression of sirtuins with longevity and lower incidence of age-related diseases such as cardiovascular, neurological and cancer.

Atherosclerosis is an immunoinflammatory process that results from a complex association of oxidized low density lipoproteins (LDLox), activated endothelial cells, monocyte-derived macrophages, T cells, and the vessel wall. Endothelial injury facilitates the entry of LDLox into the intima layer, stimulating the migration of inflammatory cells into the vessel wall and the production of inflammatory cytokines, intensifying the atherosclerotic lesion. Studies have shown that Sirt1 activation in particular, protects endothelial cells from senescence, vascular cells against DNA damage and medial degeneration for example. It is thought that Sirt1 exerts its athero-protective effects on the vessel wall by activating eNOS or by reducing cytokines activity in endothelial cells and macrophages.

SIRT1 is the most studied sirtuin due to the wide variety of protective effects on the vessel wall and its involvement in several cellular metabolic pathways. As examples, increased SIRT1 can influence various metabolic pathways that favour gluconeogenesis, reduce glycolysis and increase fatty acid oxidation. This can be in response to nutritional stimuli, particularly during calorie restriction and with phenolic compounds, and by regulating of essential metabolites such as glucose, cholesterol and fatty acids. As such, this places this protein in a central position as a universal molecular regulator that is likely to play a critical role in the systemic regulation of mammalian vascular protection.

However, further studies clarifying the mechanisms of action of Sirt1 on vascular protection are needed. Likewise, the development of new drugs may improve the pharmacological armamentarium against atherosclerotic disease. Therefore, this Research Topic aims to bring the most recent discovery on the Sirt1 mechanisms involved in vascular protection, novel pharmacological molecules that target Sirt1 for the treatment of the atherosclerosis, and animal and clinical studies related to the effects of Sirt1 against atherosclerosis.

The development of new molecules that act on Sirt1 levels can have a significant impact on reducing chronic diseases. Therefore, the proposed Research Topic on Sirt1 may be of great interest to researchers in the field of chronic degenerative diseases and also of great impact to the section of "Cardiovascular and Smooth Muscle Pharmacology" of the journal Frontiers in Pharmacology.

The intention of this Research Topic is to receive manuscripts from bench to clinical studies of interventions associated with changes in Sirt1 levels and their pathophysiological importance in the atherosclerosis process.


Keywords: Atherosclerosis, Sirtuin1, lipid metabolism, glucose metabolism disorders, animal research, clinical research


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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