Sirtuin-1 and Its Relevance in Vascular Calcification

Figures

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  Figure 1. Enzyme activity of Sirtuins-1. NAD+ receive acetyl-lysine residues from the target protein during the deacetylation process and generate nicotinamide (NAM) and 2′-O-Acetyl-ADP-ribose. NAD, Nicotinamide adenine dinucleotide and NAM, nicotinamide.

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  Figure 2. The factors contribute to the development of vascular calcification. In endothelium, endothelial-derived NO has vasodilation and antioxidant properties to protect against atherosclerosis and oxidative stress. Senescence of both ECs and VSMCs contributes to VC. Senescent VSMCs exhibit a transition into the osteoblastic phenotype, which plays a crucial role in developing vascular medial calcification. Higher calcium and higher phosphorus also lead to osteogenic phenotype transdifferentiation. PVAT has the ability to release proinflammatory adipokines and, consequently, promote VSMCs proliferation. ECM, extracellular matrix; NO, nitric oxide; NOS, NO synthase; PVAT, perivascular adipose tissue; and VSMCs, vascular smooth muscle cells.

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  Figure 3. The protective role of Sirt1 activator resveratrol in attenuating vascular calcification. In epithelial cells, Sirt1 and eNOS/NO can regulate each other in a positive feedback loop to possess significant antioxidant and anti-inflammatory properties. Sirt1 inhibit the upregulation of the p16 and p21 expression and thereby delay cell VSMCs senescence. Additionally, Sirt1 directly inhibit osteogenic phenotypic transdifferentiation of VSMCs through deacetylation of RUNX2 and β-catenin. Sirt1 protects against oxidative stress and inflammatory insult by preventing adipocytokine release through the AMPK pathway or normalizing adiponectin secretion in PVAT. AMPK, adenosine monophosphate-activated protein kinase; FoxO, Forkhead box O; GSK-3β, glycogen synthase kinase-3 beta; NO, nitric oxide; NOS, NO synthase; RUNX2, runt-related transcription factor-2; PVAT, perivascular adipose tissue; and VSMCs, vascular smooth muscle cells. (Solid arrow: promote; Dotted arrow: inhibit)