Background:Since its discovery in December 2019,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has infected more than 2180000 people worldwide and has caused more than 150000 deaths as of April 16,2020.SAR...Background:Since its discovery in December 2019,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has infected more than 2180000 people worldwide and has caused more than 150000 deaths as of April 16,2020.SARS-CoV-2,which is the virus causing coronavirus disease 2019(COVID-19),uses the angiotensin-converting enzyme 2(ACE2)as a cell receptor to invade human cells.Thus,ACE2 is the key to understanding the mechanism of SARS-CoV-2 infection.This study is to investigate the ACE2 expression in various human tissues in order to provide insights into the mechanism of SARS-CoV-2 infection.Methods:We compared ACE2 expression levels across 31 normal human tissues between males and females and between younger(ages≤49 years)and older(ages>49 years)persons using two-sided Student's t test.We also investigated the correlations between ACE2 expression and immune signatures in various tissues using Pearson's correlation test.Results:ACE2 expression levels were the highest in the small intestine,testis,kidneys,heart,thyroid,and adipose tissue,and were the lowest in the blood,spleen,bone marrow,brain,blood vessels,and muscle.ACE2 showed medium expression levels in the lungs,colon,liver,bladder,and adrenal gland.ACE2 was not differentially expressed between males and females or between younger and older persons in any tissue.In the skin,digestive system,brain,and blood vessels,ACE2 expression levels were positively associated with immune signatures in both males and females.In the thyroid and lungs,ACE2 expression levels were positively and negatively associated with immune signatures in males and females,respectively,and in the lungs they had a positive and a negative correlation in the older and younger groups,respectively.Conclusions:Our data indicate that SARS-CoV-2 may infect other tissues aside from the lungs and infect persons with different sexes,ages,and races equally.The different host immune responses to SARS-CoV-2 infection may partially explain why males and females,young and old persons infected with this vi展开更多
While severe acute respiratory syndrome coronavirus （SARS-CoV）~as initially thought to enter cells through direct fusion with the plasma membrane, more recent evidence suggests that yirus entry may also involve endo...While severe acute respiratory syndrome coronavirus （SARS-CoV）~as initially thought to enter cells through direct fusion with the plasma membrane, more recent evidence suggests that yirus entry may also involve endocytosis. We have found that SARS-CoV enters cells viapH- and receptor-dependent endocytosis. Treatment of cells with either SARS-COV spike protein or spike-bearing pseudoviruses resulted in the translocation of angiotensin-converting enzyme 2 （ACE2）, the functional receptor of SARS-CoV, from the cell surface to endosomes. In addition, the spike-bearing pseudoviruses and early endosome antigen 1 were found to colocalize in endosomes. Further analyses using specific endocytic path- way inhibitors and dominant-negative Epsl5 as well as caveolin-1 colocalization study suggested that virus entry was mediated by a clathrin- and caveolae-independent mechanism. Moreover, cholesterol- and sphingolipid-rich lipid raft microdomains in the plasma membrane, which have been shown to act as platforms for many physiological signaling pathways, were shown to be involved in virus entry. Endocytic entry of SARS-CoV may expand the cellular range of SARS-CoV infection, and our findings here contribute to the understanding of SARS-CoV pathogenesis, providing new information for anti-viral drug research.展开更多
Renin angiotensin system （RAS） activation has a significant influence on renal disease progression. The classical angiotensin-converting enzyme （ACE）-angio-tensin Ⅱ （Ang Ⅱ）-Ang Ⅱ type 1 （AT1） axis is consid...Renin angiotensin system （RAS） activation has a significant influence on renal disease progression. The classical angiotensin-converting enzyme （ACE）-angio-tensin Ⅱ （Ang Ⅱ）-Ang Ⅱ type 1 （AT1） axis is considered to control the effects of RAS activation on renal disease. However, since its discovery in 2000 ACE2 has also been demonstrated to have a significant impact on the RAS. The synthesis and catabolism of Ang Ⅱ are regulated via a complex series of interactions, which involve ACE and ACE2. In the kidneys, ACE2 is expressed in the proximal tubules and less strongly in the glomeruli. The synthesis of inactive Ang 1-9 from Ang Ⅰ and the catabolism of Ang Ⅱ to produce Ang 1-7 are the main functions of ACE2. Ang 1-7 reduces vasoconstriction, water retention, salt intake, cell proliferation, and reactive oxygen stress, and also has a renoprotective effect. Thus, in the non-classical RAS the ACE2-Ang 1-7-Mas axis counteracts the ACE-Ang Ⅱ-AT1 axis. This review examines recent human and animal studies about renal ACE and ACE2.展开更多
Objective To investigate the association of specific functional gene ACE (I/D) variants of the renin-angiotensin system with essential hypertension (EH) and interaction between ACE (I/D) gene and risk factors for EH i...Objective To investigate the association of specific functional gene ACE (I/D) variants of the renin-angiotensin system with essential hypertension (EH) and interaction between ACE (I/D) gene and risk factors for EH in a genetically homogenous Mongolia rural population of China. Methods Individuals (n=1099) were recruited from general population of Kezuohouqi Banner in Inner Mongolian Autonomous Region. Results The association was found between ACE genotype DD plus ID and EH, with an interaction between ACE genotype DD plus ID and cigarette smoking in an additive model. Cigarette smoking index and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 7.10 to 1.16. Interaction between ACE genotype DD plus ID and alcohol drinking on EH appeared an additive model. Alcohol drinking index and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 1.66 to 1.09. BMI and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 6.15 to 2.49. Interactions between ACE genotype and WHR on EH showed a multiplicative model. In a short, there was an interaction between ACE gene and cigarette smoking, alcohol drinking and BMI on EH, especially in a low dose-exposure effect Conclusion It is important for individuals who carry ACE D allele gene to prevent EH, and furthermore, to prevent and control coronary heart disease, in a view of population-based prevention.展开更多
AIM： Angiotensin II has pro-fibrotic function in the liver. Blockade of the renin-angiotensin-aldosterone-system （RAAS） attenuates hepatic fibrosis. The aim of the present study was to determine the mechanism of an...AIM： Angiotensin II has pro-fibrotic function in the liver. Blockade of the renin-angiotensin-aldosterone-system （RAAS） attenuates hepatic fibrosis. The aim of the present study was to determine the mechanism of angiotensin-converting enzyme inhibitor （ACEI） on the progression of rat hepatic fibrosis. METHODS： Forty male Wistar rats were divided into three groups. Model group （Mo）： The rats were injected subcutaneously with 40% of CCl4 0.25 mL/100 g. Perindopril group （Pe）： The rats were injected subcutaneously with 40% of CCl4. Perindopril, equivalent to 2 mg/（kg·d）, was administrated. Control group （Nc）： the rats were treated with olive oil only. After 4 and 6 wk, the rats were killed. The liver sections were stained with Masson. The protein expressions of ATIR, TGF-β1 and PDGF-BB were examined by Western blot. Nuclear factor κB （NF-κB） DNA binding activity was examined by EMSA （Electrophoretic gel mobility shift assay）. Matrix metalloproteinase-2,9 （MMP-2,9） activity was assessed by zymography. Serum laminin （LN） and hyaluronic acid （HA） were measured using radioimmunoassays. RESULTS： Using Western blot, we clearly provided direct evidence for the expression of ATIR in liver. The expression was up-regulated when fibrogenesis occurred. Perindopril treatment significantly reduced mean fibrosis score, protein levels of ATIR, TGF-β1 and PDGF-BB, serum levels of HA and LN, and the activity of MMP-2,9. NF-κB DNA bindingactivity markedly increased in model group, perindopril treatment considerably reduced NF-κB DNA binding activity.CONCLUSION： Perindopril attenuates CCl4-induced hepatic fibrogenesis of rat by inhibiting TGF-β1, PDGF-BB, NF-BB and MMP-2,9.展开更多
Background Alzheimer disease （AD） is a neurodegenerative disease related to aging. At present, its pathological mechanisms remain unclear. Family members of the renin-angiotensin system （RAS） play a role in neuron...Background Alzheimer disease （AD） is a neurodegenerative disease related to aging. At present, its pathological mechanisms remain unclear. Family members of the renin-angiotensin system （RAS） play a role in neuronal plasticity, as well as formation of learning and memory. In this study, we explore the effects of altered angiotensin-converting enzyme （ACE）, and investigate the possible mechanisms of perindopril, an ACE inhibitor, on brain structure and function in a rat model of AD, as well as the role that ACE plays in AD. Methods Sixty Sprague-Dawley rats were selected and randomly divided into 3 groups： control, AD, and perindopril. Each group consisted of 20 rats, with 10 rats for determining pathology, and the remaining 10 rats for quantifying ACE activity. The rat AD model was established by stereotactically injecting amyloid beta protein （A-beta） 1-42 into the right hippocampus. Learning and memory functions were tested using the Y-type electric maze. The number and morphology of abnormal neurons were determined by haematoxylin and eosin staining. Amyloid deposition was measured by Congo red staining. Finally, ACE activity was estimated by spectrophotometry. Results Compared with the control group, the number of times needed to escape electrical stimuli increased （23.70±3.13, P 〈0.001）, the number of normal neurons in the CA1 region was reduced （density of 96.5±32.6/mm, P 〈0.001）, amyloid deposition was obvious, and ACE activity increased （（34.4±6.6） nmol.g-1.min-1, P 〈0.001） in the AD group. In the perindopril group, the number of times needed to escape electrical stimuli decreased （18.50±3.66, P 〈0.001）, the number of abnormal neurons increased （density of CA1 neurons was 180.8±28.5/mm, P 〈0.001）, amyloid deposition was reduced, and ACE activity was down-regulated （（26.2±6.2） nmol.g-1.min-1, P 〈0.001）. Conclusions ACE activity increased in the brains of AD rats. Perindopril improved learning and memory in AD rats, which correlated with de展开更多
prevalence.A number of clinical workers and researchers have made great efforts to understand the pathogenesis and clinical characteristics and develop effective drugs for treatment.However,no effective drugs with ant...prevalence.A number of clinical workers and researchers have made great efforts to understand the pathogenesis and clinical characteristics and develop effective drugs for treatment.However,no effective drugs with antiviral effects on severe acute respiratory syndrome coronavirus 2 have been discovered currently.Traditional Chinese medicine(TCM)has gained abundant experience in the treatment of infectious diseases for thousands of years.In this review,the authors summarized the clinical outcome,pathogensis and current application of TCM on coronavirus disease 2019.Further,we discussed the potential mechanisms and the future research directions of TCM against severe acute respiratory syndrome coronavirus 2.展开更多
基金This work was supported by the China Pharmaceutical University(grant number 3150120001 to XW)。
文摘Background:Since its discovery in December 2019,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has infected more than 2180000 people worldwide and has caused more than 150000 deaths as of April 16,2020.SARS-CoV-2,which is the virus causing coronavirus disease 2019(COVID-19),uses the angiotensin-converting enzyme 2(ACE2)as a cell receptor to invade human cells.Thus,ACE2 is the key to understanding the mechanism of SARS-CoV-2 infection.This study is to investigate the ACE2 expression in various human tissues in order to provide insights into the mechanism of SARS-CoV-2 infection.Methods:We compared ACE2 expression levels across 31 normal human tissues between males and females and between younger(ages≤49 years)and older(ages>49 years)persons using two-sided Student's t test.We also investigated the correlations between ACE2 expression and immune signatures in various tissues using Pearson's correlation test.Results:ACE2 expression levels were the highest in the small intestine,testis,kidneys,heart,thyroid,and adipose tissue,and were the lowest in the blood,spleen,bone marrow,brain,blood vessels,and muscle.ACE2 showed medium expression levels in the lungs,colon,liver,bladder,and adrenal gland.ACE2 was not differentially expressed between males and females or between younger and older persons in any tissue.In the skin,digestive system,brain,and blood vessels,ACE2 expression levels were positively associated with immune signatures in both males and females.In the thyroid and lungs,ACE2 expression levels were positively and negatively associated with immune signatures in males and females,respectively,and in the lungs they had a positive and a negative correlation in the older and younger groups,respectively.Conclusions:Our data indicate that SARS-CoV-2 may infect other tissues aside from the lungs and infect persons with different sexes,ages,and races equally.The different host immune responses to SARS-CoV-2 infection may partially explain why males and females,young and old persons infected with this vi
文摘While severe acute respiratory syndrome coronavirus （SARS-CoV）~as initially thought to enter cells through direct fusion with the plasma membrane, more recent evidence suggests that yirus entry may also involve endocytosis. We have found that SARS-CoV enters cells viapH- and receptor-dependent endocytosis. Treatment of cells with either SARS-COV spike protein or spike-bearing pseudoviruses resulted in the translocation of angiotensin-converting enzyme 2 （ACE2）, the functional receptor of SARS-CoV, from the cell surface to endosomes. In addition, the spike-bearing pseudoviruses and early endosome antigen 1 were found to colocalize in endosomes. Further analyses using specific endocytic path- way inhibitors and dominant-negative Epsl5 as well as caveolin-1 colocalization study suggested that virus entry was mediated by a clathrin- and caveolae-independent mechanism. Moreover, cholesterol- and sphingolipid-rich lipid raft microdomains in the plasma membrane, which have been shown to act as platforms for many physiological signaling pathways, were shown to be involved in virus entry. Endocytic entry of SARS-CoV may expand the cellular range of SARS-CoV infection, and our findings here contribute to the understanding of SARS-CoV pathogenesis, providing new information for anti-viral drug research.
基金Supported by The Toho University School of Medicine Research Foundation
文摘Renin angiotensin system （RAS） activation has a significant influence on renal disease progression. The classical angiotensin-converting enzyme （ACE）-angio-tensin Ⅱ （Ang Ⅱ）-Ang Ⅱ type 1 （AT1） axis is considered to control the effects of RAS activation on renal disease. However, since its discovery in 2000 ACE2 has also been demonstrated to have a significant impact on the RAS. The synthesis and catabolism of Ang Ⅱ are regulated via a complex series of interactions, which involve ACE and ACE2. In the kidneys, ACE2 is expressed in the proximal tubules and less strongly in the glomeruli. The synthesis of inactive Ang 1-9 from Ang Ⅰ and the catabolism of Ang Ⅱ to produce Ang 1-7 are the main functions of ACE2. Ang 1-7 reduces vasoconstriction, water retention, salt intake, cell proliferation, and reactive oxygen stress, and also has a renoprotective effect. Thus, in the non-classical RAS the ACE2-Ang 1-7-Mas axis counteracts the ACE-Ang Ⅱ-AT1 axis. This review examines recent human and animal studies about renal ACE and ACE2.
基金This study was supported by Beijing Municipal Natural Sciences Foundation (Grant No. 7001004) Research Fund for the Doctoral Training Program from the Ministry of Education (Grant No. 20020023009) China Medical Board in New York (Grant No. 96-657).
文摘Objective To investigate the association of specific functional gene ACE (I/D) variants of the renin-angiotensin system with essential hypertension (EH) and interaction between ACE (I/D) gene and risk factors for EH in a genetically homogenous Mongolia rural population of China. Methods Individuals (n=1099) were recruited from general population of Kezuohouqi Banner in Inner Mongolian Autonomous Region. Results The association was found between ACE genotype DD plus ID and EH, with an interaction between ACE genotype DD plus ID and cigarette smoking in an additive model. Cigarette smoking index and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 7.10 to 1.16. Interaction between ACE genotype DD plus ID and alcohol drinking on EH appeared an additive model. Alcohol drinking index and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 1.66 to 1.09. BMI and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 6.15 to 2.49. Interactions between ACE genotype and WHR on EH showed a multiplicative model. In a short, there was an interaction between ACE gene and cigarette smoking, alcohol drinking and BMI on EH, especially in a low dose-exposure effect Conclusion It is important for individuals who carry ACE D allele gene to prevent EH, and furthermore, to prevent and control coronary heart disease, in a view of population-based prevention.
基金Supported by the Natural Science Foundation of China, No.30270610
文摘AIM： Angiotensin II has pro-fibrotic function in the liver. Blockade of the renin-angiotensin-aldosterone-system （RAAS） attenuates hepatic fibrosis. The aim of the present study was to determine the mechanism of angiotensin-converting enzyme inhibitor （ACEI） on the progression of rat hepatic fibrosis. METHODS： Forty male Wistar rats were divided into three groups. Model group （Mo）： The rats were injected subcutaneously with 40% of CCl4 0.25 mL/100 g. Perindopril group （Pe）： The rats were injected subcutaneously with 40% of CCl4. Perindopril, equivalent to 2 mg/（kg·d）, was administrated. Control group （Nc）： the rats were treated with olive oil only. After 4 and 6 wk, the rats were killed. The liver sections were stained with Masson. The protein expressions of ATIR, TGF-β1 and PDGF-BB were examined by Western blot. Nuclear factor κB （NF-κB） DNA binding activity was examined by EMSA （Electrophoretic gel mobility shift assay）. Matrix metalloproteinase-2,9 （MMP-2,9） activity was assessed by zymography. Serum laminin （LN） and hyaluronic acid （HA） were measured using radioimmunoassays. RESULTS： Using Western blot, we clearly provided direct evidence for the expression of ATIR in liver. The expression was up-regulated when fibrogenesis occurred. Perindopril treatment significantly reduced mean fibrosis score, protein levels of ATIR, TGF-β1 and PDGF-BB, serum levels of HA and LN, and the activity of MMP-2,9. NF-κB DNA bindingactivity markedly increased in model group, perindopril treatment considerably reduced NF-κB DNA binding activity.CONCLUSION： Perindopril attenuates CCl4-induced hepatic fibrogenesis of rat by inhibiting TGF-β1, PDGF-BB, NF-BB and MMP-2,9.
文摘Background Alzheimer disease （AD） is a neurodegenerative disease related to aging. At present, its pathological mechanisms remain unclear. Family members of the renin-angiotensin system （RAS） play a role in neuronal plasticity, as well as formation of learning and memory. In this study, we explore the effects of altered angiotensin-converting enzyme （ACE）, and investigate the possible mechanisms of perindopril, an ACE inhibitor, on brain structure and function in a rat model of AD, as well as the role that ACE plays in AD. Methods Sixty Sprague-Dawley rats were selected and randomly divided into 3 groups： control, AD, and perindopril. Each group consisted of 20 rats, with 10 rats for determining pathology, and the remaining 10 rats for quantifying ACE activity. The rat AD model was established by stereotactically injecting amyloid beta protein （A-beta） 1-42 into the right hippocampus. Learning and memory functions were tested using the Y-type electric maze. The number and morphology of abnormal neurons were determined by haematoxylin and eosin staining. Amyloid deposition was measured by Congo red staining. Finally, ACE activity was estimated by spectrophotometry. Results Compared with the control group, the number of times needed to escape electrical stimuli increased （23.70±3.13, P 〈0.001）, the number of normal neurons in the CA1 region was reduced （density of 96.5±32.6/mm, P 〈0.001）, amyloid deposition was obvious, and ACE activity increased （（34.4±6.6） nmol.g-1.min-1, P 〈0.001） in the AD group. In the perindopril group, the number of times needed to escape electrical stimuli decreased （18.50±3.66, P 〈0.001）, the number of abnormal neurons increased （density of CA1 neurons was 180.8±28.5/mm, P 〈0.001）, amyloid deposition was reduced, and ACE activity was down-regulated （（26.2±6.2） nmol.g-1.min-1, P 〈0.001）. Conclusions ACE activity increased in the brains of AD rats. Perindopril improved learning and memory in AD rats, which correlated with de
文摘prevalence.A number of clinical workers and researchers have made great efforts to understand the pathogenesis and clinical characteristics and develop effective drugs for treatment.However,no effective drugs with antiviral effects on severe acute respiratory syndrome coronavirus 2 have been discovered currently.Traditional Chinese medicine(TCM)has gained abundant experience in the treatment of infectious diseases for thousands of years.In this review,the authors summarized the clinical outcome,pathogensis and current application of TCM on coronavirus disease 2019.Further,we discussed the potential mechanisms and the future research directions of TCM against severe acute respiratory syndrome coronavirus 2.
