Background:Atherosclerosis(AS)is a chronic progressive inflammatory disease,and plaque stability plays a critical role in preventing acute events.Tanyu Tongzhi formula(TTF),a traditional Chinese medicine,has potential...Background:Atherosclerosis(AS)is a chronic progressive inflammatory disease,and plaque stability plays a critical role in preventing acute events.Tanyu Tongzhi formula(TTF),a traditional Chinese medicine,has potential therapeutic effects on AS.Methods:We used an AS animal model to examine the effects of TTF on atherosclerotic plaque vulnerability and CD40^(+)monocyte differentiation.AS plaque area,collagen content,and lipid area were assessed using histological staining.AS plaque-related biomarkers(monocyte chemoattractant protein 1(MCP-1),monocyte plus macrophage(MOMA-2),von Willebrand factor(vWF),CD31,and alpha-smooth muscle actin(α-SMA))were detected using immunohistochemistry.Inflammatory cytokines were determined using enzyme-linked immunosorbent assay.CD40 mRNA expression was detected by real-time quantitative PCR.CD40^(+)monocyte differentiation was evaluated by flow cytometry analysis in ApoE-/-mice and peripheral blood mononuclear cells(PBMCs).AMPK/NF-κB signaling pathways-related protein expression was investigated through western blotting.Results:TTF treatment reduced AS plaque area,collagen content,and lipid area in AS model mice.Levels of MCP-1,MOMA-2,vWF,and CD31 were decreased,whileα-SMA level was increased by TTF in model mice.TTF reduced inflammatory cytokines levels,including tumor necrosis factor receptor-α(TNF-α),high-sensitivity C-reactive protein(hs-CRP),and interleukin-6(IL-6).TTF inhibited CD40^(+)monocyte differentiation and decreased the number of CD40^(+)/CD40-and Ly6C^(+)/Ly6C-cells and M1/M2 ratio in AS model mice and human PBMCs.Additionally,TTF modulated the AMPK/NF-κB signaling pathway in human PBMCs.Conclusion:TTF attenuates atherosclerotic plaque vulnerability by inhibiting CD40^(+)monocyte differentiation,possibly through the regulation of the AMPK/NF-κB signaling pathway.These findings suggest that TTF could be a potential therapeutic agent for preventing plaque rupture and subsequent cardiovascular events in patients with AS.展开更多
基金Natural Science Foundation of Zhejiang Province(grant number LY20H290005)Key Research and Development Program of Zhejiang Province(grant number 2020C03119)+2 种基金National Natural Science Foundation of China(grant numbers 81673706,81973579,82174150)Science and Technology Program of Zhejiang Traditional Chinese Medicine(grant number 2018ZY005)TCM science and Technology Foundation Project of Zhejiang Province(grant number 2023ZL411).
文摘Background:Atherosclerosis(AS)is a chronic progressive inflammatory disease,and plaque stability plays a critical role in preventing acute events.Tanyu Tongzhi formula(TTF),a traditional Chinese medicine,has potential therapeutic effects on AS.Methods:We used an AS animal model to examine the effects of TTF on atherosclerotic plaque vulnerability and CD40^(+)monocyte differentiation.AS plaque area,collagen content,and lipid area were assessed using histological staining.AS plaque-related biomarkers(monocyte chemoattractant protein 1(MCP-1),monocyte plus macrophage(MOMA-2),von Willebrand factor(vWF),CD31,and alpha-smooth muscle actin(α-SMA))were detected using immunohistochemistry.Inflammatory cytokines were determined using enzyme-linked immunosorbent assay.CD40 mRNA expression was detected by real-time quantitative PCR.CD40^(+)monocyte differentiation was evaluated by flow cytometry analysis in ApoE-/-mice and peripheral blood mononuclear cells(PBMCs).AMPK/NF-κB signaling pathways-related protein expression was investigated through western blotting.Results:TTF treatment reduced AS plaque area,collagen content,and lipid area in AS model mice.Levels of MCP-1,MOMA-2,vWF,and CD31 were decreased,whileα-SMA level was increased by TTF in model mice.TTF reduced inflammatory cytokines levels,including tumor necrosis factor receptor-α(TNF-α),high-sensitivity C-reactive protein(hs-CRP),and interleukin-6(IL-6).TTF inhibited CD40^(+)monocyte differentiation and decreased the number of CD40^(+)/CD40-and Ly6C^(+)/Ly6C-cells and M1/M2 ratio in AS model mice and human PBMCs.Additionally,TTF modulated the AMPK/NF-κB signaling pathway in human PBMCs.Conclusion:TTF attenuates atherosclerotic plaque vulnerability by inhibiting CD40^(+)monocyte differentiation,possibly through the regulation of the AMPK/NF-κB signaling pathway.These findings suggest that TTF could be a potential therapeutic agent for preventing plaque rupture and subsequent cardiovascular events in patients with AS.
