Sirtuin1 in vascular endothelial function, an overview

Sirtuin1 is a nutrient-sensitive class III histone deacetylase which is a well-known regulator of organismal lifespan. It has been extensively studied for its role in metabolic regulation as well. Along with its involvement in ageing and metabolism, Sirtuin1 directly deacetylates many critical proteins controlling cardiovascular pathophysiology. Studies using conditional expression and deletion of Sirtuin1 have revealed that it functions in a highly tissue/organ-specific manner. In the vasculature, Sirtuin1 controls endothelial homoeostasis by governing the expression of inflammatory mediators, oxidants and essential transcription factors. Adding to this complexity, Sirtuin1 expression and/or function is also governed by some of these target proteins. Therefore, the importance of better understanding the organ and tissue specificity of Sirtuin1 is highly desirable. Considering the huge volume of research done in this field, this review focuses on Sirtuin1 targets regulating vascular endothelial function. Here, we summarize the discovery of Sirtuin1 as a transcription controller and the further identification of direct target proteins involved in the vascular physiology. Overall, this review presents a holistic picture of the complex cross-talk involved in the molecular regulation of vascular physiology by Sirtuin1.

Automated summary

Sirtuin1, a nutrient-sensitive histone deacetylase, serves as a key regulator of organismal lifespan and metabolic regulation. It also plays a direct role in controlling cardiovascular pathophysiology, particularly in vascular endothelial homeostasis by regulating inflammatory mediators, oxidants, and essential transcription factors. The complexity of Sirtuin1's expression and function being governed by its target proteins underscores the importance of understanding its tissue specificity for potential therapeutic interventions.