RESUMO
BACKGROUND: Hyperlipidemia damages vascular wall and serves as a foundation for diseases such as atherosclerosis, hypertension and stiffness. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is implicated in vascular dysfunction associated with hyperlipidemia-induced vascular injury. Sodium tanshinone IIA sulfonate (STS), a well-established cardiovascular protective drug with recognized anti-inflammatory, antioxidant, and vasodilatory properties, is yet to be thoroughly investigated for its impact on vascular relaxant imbalance induced by hyperlipidemia. METHODS: In this study, we treated ApoE-knockout (ApoE-/-) mouse with STS and assessed the activation of the NLRP3 inflammasome, expression of MMP2/9, integrity of elastic fibers, and vascular constriction and relaxation. RESULTS: Our findings reveal that STS intervention effectively preserves elastic fibers, significantly restores aortic relaxation function in ApoE-/- mice, and reduces their excessive constriction. Furthermore, STS inhibits the phosphorylation of spleen tyrosine kinase (SYK), suppresses NLRP3 inflammasome activation, and reduces MMP2/9 expression. CONCLUSIONS: These results demonstrate that STS protects vascular relaxation against hyperlipidemia-induced damage through modulation of the SYK-NLRP3 inflammasome-MMP2/9 pathway. This research provides novel insights into the mechanisms underlying vascular relaxation impairment in a hyperlipidemic environment and uncovers a unique mechanism by which STS preserves vascular relaxation, offering valuable foundational research evidence for its clinical application in promoting vascular health.
Assuntos
Modelos Animais de Doenças , Inflamassomos , Metaloproteinase 2 da Matriz , Metaloproteinase 9 da Matriz , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Proteína 3 que Contém Domínio de Pirina da Família NLR , Fenantrenos , Transdução de Sinais , Quinase Syk , Vasodilatação , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Quinase Syk/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Fenantrenos/farmacologia , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Vasodilatação/efeitos dos fármacos , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/fisiopatologia , Vasodilatadores/farmacologia , Fosforilação , Camundongos , Aorta/efeitos dos fármacos , Aorta/fisiopatologia , Aorta/metabolismo , Aorta/enzimologia , Apolipoproteínas ERESUMO
Three new C10 and C12 aliphatic δ-lactones (1-3), three new fatty acid methyl esters (4-6), and eight known compounds (7-14) were isolated from the marine Aureobasidium sp. LUO5. Their structures were established by detailed analyses of the NMR, HRESIMS, optical rotation, and ECD data. All isolates were tested for their inhibitory effects on nitric oxide production in LPS-induced BV-2 cells. Notably, compound 4 displayed the strongest inhibitory effect with the IC50 value of 120.3â nM.
Assuntos
Aureobasidium , Óxido Nítrico , Animais , Camundongos , Aureobasidium/química , Aureobasidium/metabolismo , Linhagem Celular , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Conformação Molecular , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Óxido Nítrico/metabolismo , LactonasRESUMO
A donor-cell-assisted membrane biotinylation strategy was used to modify small extracellular vesicles (sEVs) while minimizing protein damage, and allowed the sEVs to be loaded onto carriers. Biotinylated programmed death-ligand 1 (PD-L1) positive sEVs were used to select for aptamers from a DNA library. PD-L1 negative sEVs from a homologous cell line were found to remove non-specific aptamer sequences to increase the specificity. After just four rounds, high-affinity aptamers for PD-L1 positive sEVs were selected as novel affinity reagents.
