Role of sirtuins in attenuating plaque vulnerability in atherosclerosis

Abstract

Atherosclerosis is characterized by the development of intimal plaque, thrombosis, and stenosis of the vessel lumen causing decreased blood flow and hypoxia precipitating angina. Chronic inflammation in the stable plaque renders it unstable and rupture of unstable plaques results in the formation of emboli leading to hypoxia/ischemia to the organs by occluding the terminal branches and precipitate myocardial infarction and stroke. Such delibitating events could be controlled by the strategies that prevent plaque development or plaque stabilization. Despite the use of statins to stabilize plaques, there is a need for novel targets due to continuously increasing cases of cardiovascular events. Sirtuins (SIRTs), a family of signaling proteins, are involved in sustaining genome integrity, DNA damage response and repair, modulating oxidative stress, aging, inflammation, and energy metabolism. SIRTs play a critical role in modulating inflammation and involves in the development and progression of atherosclerosis. The role of SIRTs in relation to atherosclerosis and plaque vulnerability is scarcely discussed in the literature. Since SIRTs regulate oxidative stress, inflammation, and aging, they may also regulate plaque progression and vulnerability as these molecular mechanisms underlie the pathogenesis of plaque development, progression, and vulnerability. This review critically discusses the role of SIRTs in plaque progression and vulnerability and the possibility of targeting SIRTs to attenuate plaque rupture, focusing on the highlights in genomics, molecular pathways, and cell types involved in the underlying pathophysiology.

Sirtuins as Players in the Signal Transduction of Citrus Flavonoids

“…On these bases, SIRTs act as "cellular sensors" since, in response to stress phenomena caused by metabolic deficits or oxidative damage, they counteract aging by contributing to cell survival [14] (Figure 2). Consistent with this, changes in SIRT expression and activity are associated with pathological conditions, ranging from insulin resistance and type 2 diabetes (T2D) [15], to oxidative stress and kidney damage [16], cardiovascular and gynecological diseases [2,17,18], rheumatoid arthritis [19], neuro-inflammation [20,21], and various types of cancer [22][23][24]. In this light, a regulation of SIRT activity might support the treatment of the above-mentioned diseases.…”