Due to its good biocompatibility and degradability,magnesium alloy(Mg alloy)has shown great promise in cardiovascular stent applications.Rapid stent re-endothelialization is derived from migrated and adhered endotheli...Due to its good biocompatibility and degradability,magnesium alloy(Mg alloy)has shown great promise in cardiovascular stent applications.Rapid stent re-endothelialization is derived from migrated and adhered endothelial cells(ECs),which is an effective way to reduce late thrombosis and inhibit hyperplasia.However,fundamental questions regarding Mg alloy affecting migration and adhesion of ECs are not fully understood.Here,we evaluated the effects of Mg alloy on the ECs proliferation,adhesion and migration.A global gene expression profiling of ECs co-culturing with Mg alloy was conducted,and the adhesion-and migration-related genes were examined.We found that Mg alloy had no adverse effects on ECs viability but significantly affected ECs migration and adhesion.Co-cultured with Mg alloy extract,ECs showed contractive adhesion morphology and decreased motility,which was supported by the down-regulation of adhesion-related genes(Paxillin and Vinculin)and migration-related genes(RAC 1,Rho A and CDC 42).Accordingly,the re-endothelialization of Mg alloy stent was inhibited in vivo.Our results may provide new inspiration for improving the broad application of Mg alloy stents.展开更多
Magnesium alloy(Mg alloy)has attracted massive attention in the potential applications of cardiovascular stents because of its good biocompatibility and degradability.However,whether and how the Mg alloy induces infla...Magnesium alloy(Mg alloy)has attracted massive attention in the potential applications of cardiovascular stents because of its good biocompatibility and degradability.However,whether and how the Mg alloy induces inflammation in endothelial cells remains unclear.In the present work,we investigated the activation of Yes-associated protein(YAP)upon Mg alloy stimuli and unveiled the transcriptional function in Mg alloy-induced inflammation.Quantitative RT–PCR,western blotting and immunofluorescence staining showed that Mg alloy inhibited the Hippo pathway to facilitate nuclear shuttling and activation of YAP in human coronary artery endothelial cells(HCAECs).Chromatin immunoprecipitation followed sequencing was carried out to explore the transcriptional function of YAP in Mg alloy-derived inflammation.This led to the observation that nuclear YAP further bonded to the promoter region of inflammation transcription factors and co-transcription factors.This binding event activated their transcription and modified mRNA methylation of inflammation-related genes through regulating the expression of N6-methyladenosine modulators(METTL3,METTL14,FTO and WTAP).This then promoted inflammation-related gene expression and aggravated inflammation in HCAECs.In YAP deficiency cells,Mg alloy-induced inflammation was reduced.Collectively,our data suggest that YAP contributes to the Mg alloy-derived inflammation in HCAECs and may provide a potential therapeutic target that alleviates inflammation after Mg alloy stent implantation.展开更多
The limitations of current drug-eluting stent technologies in selectively inhibiting vascular smooth muscle cell proliferation,which often leads to inflammation,call for innovative approaches in coronary artery diseas...The limitations of current drug-eluting stent technologies in selectively inhibiting vascular smooth muscle cell proliferation,which often leads to inflammation,call for innovative approaches in coronary artery disease treatment.In the present work,we propose a revolutionary solution:a three-in-one platform for vascular stents,combining arsenic trioxide(ATO)and tacrolimus(TAC)to address anti-proliferation,pro-endothelialization,and anti-inflammation aspects.Our findings demonstrate that the synergistic action of ATO and TAC effectively suppresses aberrant vascular smooth muscle cell proliferation and mitigates endothelial cell inflammation.Remarkably,the combination treatment of TAC/ATO enhances endothelial cell migration and adhesion abilities.Moreover,our TAC/ATO-eluting stent exhibits superior re-endothelialization and anti-restenosis effects in a rabbit and porcine stent implantation model.Both in vitro and in vivo results solidify the notion that the TAC/ATO-eluting stent ensures rapid re-endothelialization and significantly reduces the incidence of in-stent restenosis.Overall,this study represents a promising and novel multifunctional platform with immense potential in the therapy of coronary artery disease.展开更多
基金This research was supported by the National Natural Science Foundation of China(11802190)National Key Research and Development Program(2016YFC1102200)the 111 Project[The Program of Introducing Talents of Discipline to Universities(B16033)].
文摘Due to its good biocompatibility and degradability,magnesium alloy(Mg alloy)has shown great promise in cardiovascular stent applications.Rapid stent re-endothelialization is derived from migrated and adhered endothelial cells(ECs),which is an effective way to reduce late thrombosis and inhibit hyperplasia.However,fundamental questions regarding Mg alloy affecting migration and adhesion of ECs are not fully understood.Here,we evaluated the effects of Mg alloy on the ECs proliferation,adhesion and migration.A global gene expression profiling of ECs co-culturing with Mg alloy was conducted,and the adhesion-and migration-related genes were examined.We found that Mg alloy had no adverse effects on ECs viability but significantly affected ECs migration and adhesion.Co-cultured with Mg alloy extract,ECs showed contractive adhesion morphology and decreased motility,which was supported by the down-regulation of adhesion-related genes(Paxillin and Vinculin)and migration-related genes(RAC 1,Rho A and CDC 42).Accordingly,the re-endothelialization of Mg alloy stent was inhibited in vivo.Our results may provide new inspiration for improving the broad application of Mg alloy stents.
基金supported by the National Natural Science Foundation of China(11802190)National Key Research and Development Program(2016YFC1102200)the 111 Project The Program of Introducing Talents of Discipline to Universities(B16033).
文摘Magnesium alloy(Mg alloy)has attracted massive attention in the potential applications of cardiovascular stents because of its good biocompatibility and degradability.However,whether and how the Mg alloy induces inflammation in endothelial cells remains unclear.In the present work,we investigated the activation of Yes-associated protein(YAP)upon Mg alloy stimuli and unveiled the transcriptional function in Mg alloy-induced inflammation.Quantitative RT–PCR,western blotting and immunofluorescence staining showed that Mg alloy inhibited the Hippo pathway to facilitate nuclear shuttling and activation of YAP in human coronary artery endothelial cells(HCAECs).Chromatin immunoprecipitation followed sequencing was carried out to explore the transcriptional function of YAP in Mg alloy-derived inflammation.This led to the observation that nuclear YAP further bonded to the promoter region of inflammation transcription factors and co-transcription factors.This binding event activated their transcription and modified mRNA methylation of inflammation-related genes through regulating the expression of N6-methyladenosine modulators(METTL3,METTL14,FTO and WTAP).This then promoted inflammation-related gene expression and aggravated inflammation in HCAECs.In YAP deficiency cells,Mg alloy-induced inflammation was reduced.Collectively,our data suggest that YAP contributes to the Mg alloy-derived inflammation in HCAECs and may provide a potential therapeutic target that alleviates inflammation after Mg alloy stent implantation.
基金National Natural Science Foundation of China(11932014,31971239)Sichuan Science and Technology Program(2022NSFSC0765,2022ZYD0079).
文摘The limitations of current drug-eluting stent technologies in selectively inhibiting vascular smooth muscle cell proliferation,which often leads to inflammation,call for innovative approaches in coronary artery disease treatment.In the present work,we propose a revolutionary solution:a three-in-one platform for vascular stents,combining arsenic trioxide(ATO)and tacrolimus(TAC)to address anti-proliferation,pro-endothelialization,and anti-inflammation aspects.Our findings demonstrate that the synergistic action of ATO and TAC effectively suppresses aberrant vascular smooth muscle cell proliferation and mitigates endothelial cell inflammation.Remarkably,the combination treatment of TAC/ATO enhances endothelial cell migration and adhesion abilities.Moreover,our TAC/ATO-eluting stent exhibits superior re-endothelialization and anti-restenosis effects in a rabbit and porcine stent implantation model.Both in vitro and in vivo results solidify the notion that the TAC/ATO-eluting stent ensures rapid re-endothelialization and significantly reduces the incidence of in-stent restenosis.Overall,this study represents a promising and novel multifunctional platform with immense potential in the therapy of coronary artery disease.
