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. 2019 Sep 12;10:1173. doi: 10.3389/fphys.2019.01173

FIGURE 2.

FIGURE 2

Pathways implicating the development of arterial remodeling and the role of SIRT1 in targeting arterial remodeling. Arterial remodeling is the structural alteration of arteries resulting from endothelial senescence/dysfunction, SMC activation, and changes in the extracellular matrix. Based on the current limited literature, SIRT1 in vascular smooth muscle cells is responsible for repressing neointima formation via a p53-PAI-1 pathway and inhibits Ang-II induced remodeling and intimal thickening. SIRT1 in vascular smooth muscle cells also prevents arterial stiffening via inhibition of NF-κB and downregulation VCAM-1 and p47phox. Endothelial SIRT1 facilitates protein complex formation with HERC2 and LKB1, which in turn, enhances LKB1 degradation and downregulation of TGFβ-signaling. SIRT1-HERC2-LKB1 axis prevents arterial remodeling by targeting endothelial senescence and SMC activation. NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells. VCAM-1, vascular cell adhesion protein 1. AngII, angiotensin II. MMP, matrix metalloproteinase. PAI-1, plasminogen activator inhibitor-1. TGFβ, transforming growth factor-beta. NO, nitric oxide. PDGF, platelet-derived growth factor. HERC2, HECT and RLD domain containing E3 ubiquitin-protein ligase 2.