Induced pluripotent stem cells(iPSCs) were first generated by Yamanaka and colleagues over a decade ago. Since then, iPSCs have been successfully differentiated into many distinct cell types, enabling tissue-, disease...Induced pluripotent stem cells(iPSCs) were first generated by Yamanaka and colleagues over a decade ago. Since then, iPSCs have been successfully differentiated into many distinct cell types, enabling tissue-, disease-, and patientspecific in vitro modelling. Cardiovascular disease is the greatest cause of mortality worldwide but encompasses rarer disorders of conduction and myocardial function for which a cellular model of study is ideal. Although methods to differentiate iPSCs into beating cardiomyocytes(iPSC-CMs) have recently been adequately optimized and commercialized, the resulting cells remain largely immature with regards to their structure and function,demonstrating fetal gene expression, disorganized morphology, reliance on predominantly glycolytic metabolism and contractile characteristics that differ from those of adult cardiomyocytes. As such, disease modelling using iPSC-CMs may be inaccurate and of limited utility. However, this limitation is widely recognized, and numerous groups have made substantial progress in addressing this problem. This review highlights successful methods that have been developed for the maturation of human iPSC-CMs using small molecules,environmental manipulation and 3-dimensional(3 D) growth approaches.展开更多
Atherosclerotic cardiovascular disease(ASCVD) is the deadliest disease in the world, with endothelial injury occurring throughout the course of the disease. Therefore, improvement in endothelial function is of essenti...Atherosclerotic cardiovascular disease(ASCVD) is the deadliest disease in the world, with endothelial injury occurring throughout the course of the disease. Therefore, improvement in endothelial function is of essential importance in the prevention of ASCVD. Red yeast rice(RYR), a healthy traditional Chinese food, has a lipid modulation function and also plays a vital role in the improvement of endothelial reactivity and cardiovascular protection; thus, it is significant in the prevention and treatment of ASCVD. This article reviews the molecular mechanisms of RYR and its related products in the improvement of endothelial function in terms of endothelial reactivity, anti-apoptosis of endothelial progenitor cells, oxidative stress alleviation and anti-inflammation.展开更多
The genetic cardiomyopathies are a group of disorders related by abnormal myocardial structure and function.Although individually rare,these diseases collectively represent a significant health burden since they usual...The genetic cardiomyopathies are a group of disorders related by abnormal myocardial structure and function.Although individually rare,these diseases collectively represent a significant health burden since they usually develop early in life and are a major cause of morbidity and mortality amongst affected children.The heterogeneity and rarity of these disorders requires the use of an appropriate model system in order to characterize the mechanism of disease and develop useful therapeutics since standard drug trials are infeasible.A common approach to study human disease involves the use of animal models,especially rodents,but due to important biological and physiological differences,this model system may not recapitulate human disease.An alternative approach for studying the metabolic cardiomyopathies relies on the use of cellular models which have most frequently been immortalized cell lines or patient-derived fibroblasts.However,the recent introduction of induced pluripotent stem cells(iPSCs),which have the ability to differentiate into any cell type in the body,is of great interest and has the potential to revolutionize the study of rare diseases.In this paper we review the advantages and disadvantages of each model system by comparing their utility for the study of mitochondrial cardiomyopathy with a particular focus on the use of iPSCs in cardiovascular biology for the modeling of rare genetic or metabolic diseases.展开更多
Objective:Our previous research showed that Naotaifang(a compound traditional Chinese herbal medicine)extract(NTE)has clinically beneficial effects on neurological improvement of patients with acute cerebral ischemia....Objective:Our previous research showed that Naotaifang(a compound traditional Chinese herbal medicine)extract(NTE)has clinically beneficial effects on neurological improvement of patients with acute cerebral ischemia.In this study,we investigated whether NTE protected acute brain injury in rats and whether its effects on ferroptosis could be linked to the dysfunction of glutathione peroxidase 4(GPX4)and iron metabolism.Methods:We established an acute brain injury model of middle cerebral artery occlusion(MCAO)in rats,in which we could observe the accumulation of iron in neurons,as detected by Perl’s staining.Using assay kits,we measured expression levels of ferroptosis biomarkers,such as iron,glutathione(GSH),reactive oxygen species(ROS)and malonaldehyde(MDA);further the expression levels of transferrin receptor1(TFR1),divalent metal transporter 1(DMT1),solute carrier family 7 member 11(SLC7 A11)and GPX4 were determined using immunohistochemical analysis,real-time quantitative polymerase chain reaction and Western blot assays.Results:We found that treatment with NTE reduced the expression levels of TFR1 and DMT1,reduced ROS,MDA and iron accumulation and reduced neurobehavioral scores,relative to untreated MCAO rats.Treatment with NTE increased the expression levels of SLC7 A11,GPX4 and GSH,and the number of Nissl bodies in the MCAO rats.Conclusion:Taken together,our data suggest that acute cerebral ischemia induces neuronal ferroptosis and the effects of treating MCAO rats with NTE involved inhibition of ferroptosis through the TFR1/DMT1 and SCL7 A11/GPX4 pathways.展开更多
基金Supported by Children’s Cardiomyopathy Foundation,No.2017
文摘Induced pluripotent stem cells(iPSCs) were first generated by Yamanaka and colleagues over a decade ago. Since then, iPSCs have been successfully differentiated into many distinct cell types, enabling tissue-, disease-, and patientspecific in vitro modelling. Cardiovascular disease is the greatest cause of mortality worldwide but encompasses rarer disorders of conduction and myocardial function for which a cellular model of study is ideal. Although methods to differentiate iPSCs into beating cardiomyocytes(iPSC-CMs) have recently been adequately optimized and commercialized, the resulting cells remain largely immature with regards to their structure and function,demonstrating fetal gene expression, disorganized morphology, reliance on predominantly glycolytic metabolism and contractile characteristics that differ from those of adult cardiomyocytes. As such, disease modelling using iPSC-CMs may be inaccurate and of limited utility. However, this limitation is widely recognized, and numerous groups have made substantial progress in addressing this problem. This review highlights successful methods that have been developed for the maturation of human iPSC-CMs using small molecules,environmental manipulation and 3-dimensional(3 D) growth approaches.
基金supported by Clinical Vascular Grant In Chinese Physicians-VG(No.2017-CCA-VG-016)the Basic and Clinical Research Cooperation Project of Capital Medical University(No.16JL42)the Presidential Foundation of Beijing Anzhen Hospital Affiliated with Capital Medical University(No.2016P01)
文摘Atherosclerotic cardiovascular disease(ASCVD) is the deadliest disease in the world, with endothelial injury occurring throughout the course of the disease. Therefore, improvement in endothelial function is of essential importance in the prevention of ASCVD. Red yeast rice(RYR), a healthy traditional Chinese food, has a lipid modulation function and also plays a vital role in the improvement of endothelial reactivity and cardiovascular protection; thus, it is significant in the prevention and treatment of ASCVD. This article reviews the molecular mechanisms of RYR and its related products in the improvement of endothelial function in terms of endothelial reactivity, anti-apoptosis of endothelial progenitor cells, oxidative stress alleviation and anti-inflammation.
基金Supported by Children’s Cardiomyopathy Foundation
文摘The genetic cardiomyopathies are a group of disorders related by abnormal myocardial structure and function.Although individually rare,these diseases collectively represent a significant health burden since they usually develop early in life and are a major cause of morbidity and mortality amongst affected children.The heterogeneity and rarity of these disorders requires the use of an appropriate model system in order to characterize the mechanism of disease and develop useful therapeutics since standard drug trials are infeasible.A common approach to study human disease involves the use of animal models,especially rodents,but due to important biological and physiological differences,this model system may not recapitulate human disease.An alternative approach for studying the metabolic cardiomyopathies relies on the use of cellular models which have most frequently been immortalized cell lines or patient-derived fibroblasts.However,the recent introduction of induced pluripotent stem cells(iPSCs),which have the ability to differentiate into any cell type in the body,is of great interest and has the potential to revolutionize the study of rare diseases.In this paper we review the advantages and disadvantages of each model system by comparing their utility for the study of mitochondrial cardiomyopathy with a particular focus on the use of iPSCs in cardiovascular biology for the modeling of rare genetic or metabolic diseases.
基金supported by the National Natural Science Foundation of China(No.81774033 and No.81773736)the Hunan Provincial Department of Education-funded Scientific Research Project(No.18C0379 and No.19A378)。
文摘Objective:Our previous research showed that Naotaifang(a compound traditional Chinese herbal medicine)extract(NTE)has clinically beneficial effects on neurological improvement of patients with acute cerebral ischemia.In this study,we investigated whether NTE protected acute brain injury in rats and whether its effects on ferroptosis could be linked to the dysfunction of glutathione peroxidase 4(GPX4)and iron metabolism.Methods:We established an acute brain injury model of middle cerebral artery occlusion(MCAO)in rats,in which we could observe the accumulation of iron in neurons,as detected by Perl’s staining.Using assay kits,we measured expression levels of ferroptosis biomarkers,such as iron,glutathione(GSH),reactive oxygen species(ROS)and malonaldehyde(MDA);further the expression levels of transferrin receptor1(TFR1),divalent metal transporter 1(DMT1),solute carrier family 7 member 11(SLC7 A11)and GPX4 were determined using immunohistochemical analysis,real-time quantitative polymerase chain reaction and Western blot assays.Results:We found that treatment with NTE reduced the expression levels of TFR1 and DMT1,reduced ROS,MDA and iron accumulation and reduced neurobehavioral scores,relative to untreated MCAO rats.Treatment with NTE increased the expression levels of SLC7 A11,GPX4 and GSH,and the number of Nissl bodies in the MCAO rats.Conclusion:Taken together,our data suggest that acute cerebral ischemia induces neuronal ferroptosis and the effects of treating MCAO rats with NTE involved inhibition of ferroptosis through the TFR1/DMT1 and SCL7 A11/GPX4 pathways.
