Beyond longevity: novel roles of Sirtuin-3 in thrombosis

Extract

This editorial refers to ‘Loss of Sirt3 accelerates arterial thrombosis by increasing formation of neutrophil extracellular traps and plasma tissue factor activity’ by D.S. Gaul et al., pp. 1178–1188.

Sirtuins comprise a highly conserved family of proteins with protective effects in ageing and cardiovascular diseases.¹ Sirtuin-3 (SIRT3) is a mitochondrial isoform that catalyses protein deacetylation using nicotinamide adenine dinucleotide (NAD⁺) as a co-substrate. It acts as a sensor of energy balance and redox state, to regulate post-translational protein modifications and thereby influences diverse metabolic pathways.

In humans, genetic polymorphism increasing SIRT3 expression has been associated with an increased lifespan,² whereas mutations that reduce SIRT3 activity have been associated with myocardial infarction³ and metabolic syndrome.⁴ In rodents, global SIRT3-deficiency has been mainly associated with cardiac deterioration. SIRT3-knockout mice develop spontaneous cardiac hypertrophy and fibrosis with age.⁵ Moreover, these animals also exhibit adverse outcomes when challenged with pressure overload stimuli⁶ or when subjected to experimental myocardial infarction.⁷