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Figure 1. Restoration of PINK1/Parkin-associated mitophagy via the NAD⁺/SIRT1 axis attenuates KD vasculitis. In the LCWE murine model of KD, cardiovascular lesions are characterized by depletion of circulating NAD⁺ precursors (nicotinamide, 1-methylnicotinamide, nicotinamide N-oxide) and downregulation of the NAD⁺-dependent deacetylase SIRT1 in heart and abdominal aortic tissue (left panel). In VSMCs, low SIRT1 permits the pathogenic synthetic phenotypic switch from contractile type-I VSMCs (αSMA+, Myh11+) to synthetic type-II VSMCs (MMP3/14 up), contributing to luminal myofibroblast proliferation and coronary stenosis. In macrophages, impaired mitophagy leads to accumulation of damaged mitochondria that release mtDNA and ROS, activating the NLRP3 inflammasome and driving caspase-1-dependent maturation and secretion of IL-1β. Restoring the NAD⁺/SIRT1 axis through four complementary interventions (middle panel), constitutive SIRT1 overexpression (Sirt1super mice), tamoxifen-inducible SIRT1-ER activation (Sirt1ER/ER mice), pharmacological SIRT1 activation (SRT1720, resveratrol), or NAD⁺ precursor supplementation (NR, β-NMN), rescues the diseased phenotype (right panel). SIRT1 activation restores PINK1/Parkin-mediated mitophagic flux, clearing damaged mitochondria, suppressing NLRP3 inflammasome activity and IL-1β production, and preserving the contractile VSMC identity, thereby reducing coronary arteritis, abdominal aortic dilation, immune cell infiltration, and cardiac dysfunction. Cell-type-specific deletion of Sirt1 in VSMCs (Myh11-Cre/ERT2) or myeloid cells (Csf1r-Cre) exacerbates LCWE-induced vasculitis, confirming that both compartments are non-redundant nodes of SIRT1-dependent protection. The figure was created using LibreOffice and Inkscape. PINK1: PTEN-induced kinase 1; NAD⁺: nicotinamide adenine dinucleotide; SIRT1: Sirtuin 1; KD: Kawasaki disease; LCWE: Lactobacillus casei cell wall extract; VSMCs: vascular smooth muscle cells; αSMA+: alpha-smooth muscle actin-positive; MMP3/14: matrix metalloproteinase 3/14; mtDNA: mitochondrial DNA; ROS: reactive oxygen species; NLRP3: NOD-like receptor family pyrin domain containing 3; IL-1β: interleukin-1β; NR: nicotinamide riboside; β-NMN: β-nicotinamide mononucleotide.