Sirtuin 1 steers anti-inflammatory effects in vascular smooth muscle cells: protection without burden?

Extract

This editorial refers to ‘CKII-SIRT1-SM22α loop evokes a self-limited inflammatory response in vascular smooth muscle cells’ by Y.N. Shu et al., pp. 1198–1207

SirT1 (mammalian homolog of silent information regulator 1 protein) is a nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylase which is highly expressed in vascular smooth muscle cells (VSMCs), and is considered as an important negative regulator of neointimal hyperplasia. The general concept attributing protective effects to SirT1 in VSMC function appears complex in terms of mechanisms since several direct and indirect molecular pathways contribute to the effects of SirT1 which are multifaceted. Several studies speculate that SirT1 and other molecules form a network which is necessary for its protective effects.¹ Thus, elucidation of these interactions within the network is required for the development of sirtuin-activating compounds (STACs).² The same comment may be formulated at the level of inflammatory cells and platelets present in the vascular wall during development of atherosclerosis, abdominal aortic aneurysm, vascular senescence, arterial stiffness and angiotensin II-induced medial hypertrophy.^3–6 SirT1 is localized predominantly in the nucleus and exerts its function through transcriptional mechanisms and epigenetic signalling pathways.¹ In contrast to Sirt1-mediated transcription regulation, the involvement of epigenetic factors has not been so far identified in neointimal hyperplasia.