Eur J Pharmacol. 2023 Aug 23 ;957:175965. Epub 2023 Aug 23. PMID: 37625682
Melatonin ameliorates atherosclerosis by suppressing S100a9-mediated vascular irritation.
Atherosclerosis (AS)-associated cardiovascular ailments are predominant causes of morbidity and mortality worldwide. Melatonin, a circadian hormone with anti-inflammatory exercise, could also be a novel therapeutic intervention for AS. Nonetheless, the precise mechanism is unclear. This analysis supposed to research the mechanism of melatonin in treating AS. Melatonin (20 mg/kg/d) was intraperitoneally administered in a high-fat food regimen (HFD)-induced AS mannequin utilizing apolipoprotein E-deficient (ApoE) mice for 12 weeks. Immunohistochemical and immunofluorescence analyses, data-independent acquisition (DIA)-based protein profiling, ingenuity pathway evaluation (IPA), and western blotting had been employed to research the therapeutic results of melatonin in treating HFD-induced AS. An adeno-associated virus (AAV) vector was additional used to substantiate the antiatherosclerotic mechanism of melatonin. Melatonin therapy markedly attenuated atherosclerotic lesions, induced steady phenotypic sclerotic plaques, inhibited macrophage infiltration, and suppressed the manufacturing of proinflammatory cytokines in ApoEmice with HFD-induced AS. Notably, DIA-based quantitative proteomics along with IPA recognized S100a9 as a pivotal mediator within the protecting results of melatonin. Furthermore, melatonin considerably suppressed HFD-induced S100a9 expression at each the mRNA and protein ranges. The overexpression of S100a9 considerably activated the NF-κB signaling pathway and markedly abolished the antagonistic impact of melatonin on HFD-induced vascular irritation throughout atherogenesis. Melatonin exerts a big antiatherogenic impact by inhibiting S100a9/NF-κB signaling pathway-mediated vascular irritation. Our findings reveal a novel antiatherosclerotic mechanism of melatonin and underlie its potential scientific use in modulating AS with good availability and affordability.