Atherosclerosis serves as the core pathological basis of cardiovascular,cerebrovascular,and peripheral arterial diseases,posing a serious threat to human health.However,current mainstream treatments such as statin dru...Atherosclerosis serves as the core pathological basis of cardiovascular,cerebrovascular,and peripheral arterial diseases,posing a serious threat to human health.However,current mainstream treatments such as statin drugs and stent implantation are associated with significant side effects or limited efficacy,highlighting the urgent need for new therapeutic strategies.Pulsed electromagnetic fields(PEMFs),due to their noninvasive nature and anti-inflammatory properties,show potential in the treatment of atherosclerosis.This study utilized ApoE-/-mice,ApoE-/-NLRP3-/-knockout mice,human umbilical vein endothelial cells(HUVECs),human aortic endothelial cells(HAECs),and human plasma samples for experiments,revealing significant endothelial cell(EC)inflammation and pyroptosis during the progression of atherosclerosis.PEMFs were found to effectively inhibit the activation of the NLRP3 inflammasome,reduce plaque formation,and delay the progression of atherosclerosis.Proteomic analysis of plasma from atherosclerosis patients further indicated elevated expression levels of proteins related to inflammation and pyroptosis,with particularly notable changes in membrane proteins.Mechanistic studies demonstrated that PEMFs improve mitochondrial dysfunction in ECs by regulating membrane tension and the mechanosensitive tension-mediated transient receptor potential vanilloid 4(TRPV4)channels,thereby reducing pyroptosis.This discovery not only reveals a novel mechanobiological pathway but also provides a solid theoretical foundation for the development of PEMF-based therapies for atherosclerosis.展开更多
基金supported by the National Key Research and Development Program of China(Grant No.2023YFC3603800 and 2023YFC3603801)the National Natural Science Foundation of China(Grant No.82372574,82172534,82202792,and 82202793)+1 种基金the Natural Science Foundation of Sichuan Province(Grant No.2024NSFSC0534)the Natural Science Foundation Innovation Group of Sichuan Province(Grant No.2023NSFSC1999).
文摘Atherosclerosis serves as the core pathological basis of cardiovascular,cerebrovascular,and peripheral arterial diseases,posing a serious threat to human health.However,current mainstream treatments such as statin drugs and stent implantation are associated with significant side effects or limited efficacy,highlighting the urgent need for new therapeutic strategies.Pulsed electromagnetic fields(PEMFs),due to their noninvasive nature and anti-inflammatory properties,show potential in the treatment of atherosclerosis.This study utilized ApoE-/-mice,ApoE-/-NLRP3-/-knockout mice,human umbilical vein endothelial cells(HUVECs),human aortic endothelial cells(HAECs),and human plasma samples for experiments,revealing significant endothelial cell(EC)inflammation and pyroptosis during the progression of atherosclerosis.PEMFs were found to effectively inhibit the activation of the NLRP3 inflammasome,reduce plaque formation,and delay the progression of atherosclerosis.Proteomic analysis of plasma from atherosclerosis patients further indicated elevated expression levels of proteins related to inflammation and pyroptosis,with particularly notable changes in membrane proteins.Mechanistic studies demonstrated that PEMFs improve mitochondrial dysfunction in ECs by regulating membrane tension and the mechanosensitive tension-mediated transient receptor potential vanilloid 4(TRPV4)channels,thereby reducing pyroptosis.This discovery not only reveals a novel mechanobiological pathway but also provides a solid theoretical foundation for the development of PEMF-based therapies for atherosclerosis.
