Background:Vascular smooth muscle cells(VSMCs)undergo a conversion from a contractile phenotype to a proliferative synthetic phenotype,contributing to the pathogenesis of cardiovascular diseases.Semaphorin 7A(SEMA7A)i...Background:Vascular smooth muscle cells(VSMCs)undergo a conversion from a contractile phenotype to a proliferative synthetic phenotype,contributing to the pathogenesis of cardiovascular diseases.Semaphorin 7A(SEMA7A)is a glycosylphosphatidylinositol-anchored membrane protein that plays an important role in vascular homeostasis by regulating endothelial cell behaviors.However,the expression and role of SEMA7A in VSMCs remain unclear.Methods:In this study,we screened for VSMC-regulating genes in publicly available datasets and analyzed the expression of SEMA7A in human coronary artery smooth muscle cells(hCASMCs)treated with platelet-derived growth factor-BB(PDGF-BB).The effects of SEMA7A overexpression and knockdown on hCASMC proliferation and migration were examined.The signaling pathways involved in the action of SEMA7A in hCASMCs were determined.Results:Bioinformatic analysis showed that SEMA7A was significantly dysregulated in VSMCs treated with oxidized low-density lipoprotein or overexpressing progerin,a pro-atherogenic gene.The PDGF-BB stimulation led to a concentration-and time-dependent induction of SEMA7A.Depletion of SEMA7A attenuated PDGF-BB-induced hCASMC proliferation and migration.Conversely,overexpression of SEMA7A enhanced hCASMC proliferation and migration.Mechanistically,SEMA7A stimulated the activation of theβ-catenin pathway and upregulated c-Myc,CCND1,and MMP7.Knockdown ofβ-catenin impaired SEMA7A-induced hCASMC proliferation and migration.Conclusions:SEMA7A triggers phenotype switching in VSMCs through theβ-catenin signaling pathway and may serve as a potential therapeutic target for cardiovascular diseases.展开更多
Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus-2(SARS-CoV-2),has rapidly become a global health emergency.In addition to causing respiratory effects,SARS-CoV-2 can result in...Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus-2(SARS-CoV-2),has rapidly become a global health emergency.In addition to causing respiratory effects,SARS-CoV-2 can result in cardiac involvement leading to myocardial damage,which is increasingly being explored in the literature.Myocardial injury is an important pathogenic feature of COVID-19.The angiotensin-converting enzyme-2 receptor plays a key role in the pathogenesis of the virus,serving as a"bridge"allowing SARS-CoV-2 to invade the body.However,the exact mechanism underlying how SARS-CoV-2 causes myocardial injury remains unclear.This review summarizes the main possible mechanisms of myocardial injury in patients with COVID-19,including direct myocardial cell injury,microvascular dysfunction,cytokine responses and systemic inflammation,hypoxemia,stress responses,and drug-induced myocardial injury.Understanding of the underlying mechanisms would aid in proper identification and treatment of myocardial injury in patients with COVID-19.展开更多
基金supported by the Basic Research Program of Shanxi Province(Free Exploration)of China(20210302124416)Science and Technology Grant for Selected Returned Chinese Scholars of Shanxi Province of China(20220043)Four“Batches”Innovation Project of Invigorating Medical through Science and Technology of Shanxi Province of China(2022XM08).
文摘Background:Vascular smooth muscle cells(VSMCs)undergo a conversion from a contractile phenotype to a proliferative synthetic phenotype,contributing to the pathogenesis of cardiovascular diseases.Semaphorin 7A(SEMA7A)is a glycosylphosphatidylinositol-anchored membrane protein that plays an important role in vascular homeostasis by regulating endothelial cell behaviors.However,the expression and role of SEMA7A in VSMCs remain unclear.Methods:In this study,we screened for VSMC-regulating genes in publicly available datasets and analyzed the expression of SEMA7A in human coronary artery smooth muscle cells(hCASMCs)treated with platelet-derived growth factor-BB(PDGF-BB).The effects of SEMA7A overexpression and knockdown on hCASMC proliferation and migration were examined.The signaling pathways involved in the action of SEMA7A in hCASMCs were determined.Results:Bioinformatic analysis showed that SEMA7A was significantly dysregulated in VSMCs treated with oxidized low-density lipoprotein or overexpressing progerin,a pro-atherogenic gene.The PDGF-BB stimulation led to a concentration-and time-dependent induction of SEMA7A.Depletion of SEMA7A attenuated PDGF-BB-induced hCASMC proliferation and migration.Conversely,overexpression of SEMA7A enhanced hCASMC proliferation and migration.Mechanistically,SEMA7A stimulated the activation of theβ-catenin pathway and upregulated c-Myc,CCND1,and MMP7.Knockdown ofβ-catenin impaired SEMA7A-induced hCASMC proliferation and migration.Conclusions:SEMA7A triggers phenotype switching in VSMCs through theβ-catenin signaling pathway and may serve as a potential therapeutic target for cardiovascular diseases.
基金This work was supported by the National Natural Science Foundation of China(grant No.81970391)Basic Research Program of Shanxi Province(Free Exploration)(grant No.20210302124416)Science and Technology grant for Selected Returned Chinese Researchers of Shanxi Province(grant No.20220043).
文摘Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus-2(SARS-CoV-2),has rapidly become a global health emergency.In addition to causing respiratory effects,SARS-CoV-2 can result in cardiac involvement leading to myocardial damage,which is increasingly being explored in the literature.Myocardial injury is an important pathogenic feature of COVID-19.The angiotensin-converting enzyme-2 receptor plays a key role in the pathogenesis of the virus,serving as a"bridge"allowing SARS-CoV-2 to invade the body.However,the exact mechanism underlying how SARS-CoV-2 causes myocardial injury remains unclear.This review summarizes the main possible mechanisms of myocardial injury in patients with COVID-19,including direct myocardial cell injury,microvascular dysfunction,cytokine responses and systemic inflammation,hypoxemia,stress responses,and drug-induced myocardial injury.Understanding of the underlying mechanisms would aid in proper identification and treatment of myocardial injury in patients with COVID-19.
