Fig. 1.

Inflammatory pathway leading to cascade resulting in plaque vulnerability and the effect of Sirtuins attenuating pro-inflammatory mediators. Intimal injury during vascular intervention or during atherogenesis induce release of DAMPs which stimulate inflammatory signaling by activating Toll-like receptors (TLRs) and receptor for advanced glycation end-products (RAGE) leading to immune response involving increased recruitment of innate and adaptive immune cells, secretion of pro-inflammatory cytokines, and NLRP3 inflammasome activation. Altogether, they cause chronic inflammation in the plaque and induce vulnerability. Intimal injury also causes disruption of vasa-vasorum and leads to hypoxia and oxidative stress which in turn activate sirtuins. Increased sirtuins act as oxidative stress scavenger and reduce oxygen radicals and decrease oxidative stress which may lead to attenuated plaque vulnerability