Pub Date : 2020-06-17eCollection Date: 2020-04-01DOI: 10.1177/1470320320934716
Jian Xu, Jiming Chen, Yilu Li, Dandan Zhang, Xiaoli Li
Introduction: Many studies have investigated the association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and susceptibility to obstructive sleep apnoea (OSA). However, few have confirmed the relationship between ACE and OSA in the Chinese population. We performed a meta-analysis of studies relating the ACE I/D polymorphism to the risk of OSA in a Chinese population.
Methods: We evaluated eligible published studies from several databases for this meta-analysis. Subgroup analyses were performed for hypertension. Pooled odds ratios and 95% confidence intervals were calculated using a fixed- or random-effects model.
Results: Ten studies were identified to analyse the association between ACE I/D polymorphism and OSA risk. No marked associations were found in any genetic model (p>0.05). Subgroup analysis showed an association with hypertension (D vs. I, DD vs. II, ID vs. DD+II, DD+ID vs. II, ID vs. II; p<0.05), which was confirmed by sensitivity analyses. No obvious publication bias was found using Egger's test (p>0.05).
Conclusions: The ACE I/D polymorphism was not associated with an increased risk of OSA in a Chinese population. However, within the hypertensive subgroup, we detected a significant association between the ACE polymorphism and OSA. More case-control investigations are required.
许多研究探讨了血管紧张素转换酶(ACE)基因插入/缺失(I/D)多态性与阻塞性睡眠呼吸暂停(OSA)易感性之间的关系。然而,很少有人证实ACE与OSA在中国人群中的关系。我们对中国人群中ACE I/D多态性与OSA风险相关的研究进行了荟萃分析。方法:我们从几个数据库中评估了符合条件的已发表研究。对高血压进行亚组分析。合并优势比和95%置信区间使用固定或随机效应模型计算。结果:10项研究分析了ACE I/D多态性与OSA风险的关系。各遗传模型均无显著相关性(p>0.05)。亚组分析显示与高血压相关(D vs. I, DD vs. II, ID vs. DD+II, DD+ID vs. II, ID vs. II;页> 0.05)。结论:在中国人群中,ACE I/D多态性与OSA风险增加无关。然而,在高血压亚组中,我们发现ACE多态性与OSA之间存在显著关联。需要进行更多的病例对照调查。
{"title":"Association of angiotensin-converting enzyme gene insertion/deletion polymorphism and obstructive sleep apnoea in a Chinese population: A meta-analysis.","authors":"Jian Xu, Jiming Chen, Yilu Li, Dandan Zhang, Xiaoli Li","doi":"10.1177/1470320320934716","DOIUrl":"https://doi.org/10.1177/1470320320934716","url":null,"abstract":"<p><strong>Introduction: </strong>Many studies have investigated the association between angiotensin-converting enzyme (<i>ACE</i>) gene insertion/deletion (I/D) polymorphism and susceptibility to obstructive sleep apnoea (OSA). However, few have confirmed the relationship between ACE and OSA in the Chinese population. We performed a meta-analysis of studies relating the <i>ACE</i> I/D polymorphism to the risk of OSA in a Chinese population.</p><p><strong>Methods: </strong>We evaluated eligible published studies from several databases for this meta-analysis. Subgroup analyses were performed for hypertension. Pooled odds ratios and 95% confidence intervals were calculated using a fixed- or random-effects model.</p><p><strong>Results: </strong>Ten studies were identified to analyse the association between <i>ACE</i> I/D polymorphism and OSA risk. No marked associations were found in any genetic model (<i>p</i>>0.05). Subgroup analysis showed an association with hypertension (D vs. I, DD vs. II, ID vs. DD+II, DD+ID vs. II, ID vs. II; <i>p</i><0.05), which was confirmed by sensitivity analyses. No obvious publication bias was found using Egger's test (<i>p</i>>0.05).</p><p><strong>Conclusions: </strong>The <i>ACE</i> I/D polymorphism was not associated with an increased risk of OSA in a Chinese population. However, within the hypertensive subgroup, we detected a significant association between the <i>ACE</i> polymorphism and OSA. More case-control investigations are required.</p>","PeriodicalId":17330,"journal":{"name":"Journal of the Renin-Angiotensin-Aldosterone System","volume":"21 2","pages":"1470320320934716"},"PeriodicalIF":2.9,"publicationDate":"2020-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1470320320934716","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38889136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-05-16DOI: 10.5772/intechopen.92309
Vedran Đambić, Đorđe Pojatić, Anto Stažić, Aleksandar Kibel
The renin-angiotensin system, in both its circulating and local tissue roles, is intertwined with multiple other regulatory and signalling mechanisms in various tissues and organ systems. It plays a central role in the normal regulation of arterial blood pressure and in the development of hypertension, which is an immense global public health burden and a crucial modifiable risk factor in the development of cardiovascular diseases. The renin-angiotensin system plays also important roles in a range of other clinical conditions such as heart failure, kidney failure, diabetes mellitus and others. Therapeutic interventions within the renin-angiotensin system include the use of medications such as angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists, which are well established and have been invaluable as clinically effective tools during many years of practical use. Additionally, numerous other therapeutic approaches targeting components of the renin-angiotensin system have been developed or are currently in development. This chapter will discuss details of the roles of this system in the most relevant clinical conditions.
{"title":"Significance of the Renin-Angiotensin System in Clinical Conditions","authors":"Vedran Đambić, Đorđe Pojatić, Anto Stažić, Aleksandar Kibel","doi":"10.5772/intechopen.92309","DOIUrl":"https://doi.org/10.5772/intechopen.92309","url":null,"abstract":"The renin-angiotensin system, in both its circulating and local tissue roles, is intertwined with multiple other regulatory and signalling mechanisms in various tissues and organ systems. It plays a central role in the normal regulation of arterial blood pressure and in the development of hypertension, which is an immense global public health burden and a crucial modifiable risk factor in the development of cardiovascular diseases. The renin-angiotensin system plays also important roles in a range of other clinical conditions such as heart failure, kidney failure, diabetes mellitus and others. Therapeutic interventions within the renin-angiotensin system include the use of medications such as angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists, which are well established and have been invaluable as clinically effective tools during many years of practical use. Additionally, numerous other therapeutic approaches targeting components of the renin-angiotensin system have been developed or are currently in development. This chapter will discuss details of the roles of this system in the most relevant clinical conditions.","PeriodicalId":17330,"journal":{"name":"Journal of the Renin-Angiotensin-Aldosterone System","volume":"2012 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2020-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73515393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Adrenal venous sampling is useful for discriminating unilateral and bilateral hypersecretion in patients with primary aldosteronism, but it is relatively invasive. To determine the site of hypersecretion more non-invasively, we evaluated predictors of unilateral hypersecretion.
Materials and methods: We evaluated the baseline characteristics and the results of confirmatory tests of 123 patients with primary aldosteronism who underwent adrenal venous sampling.
Results: Unilateral hypersecretion was identified in 22.0%. The plasma aldosterone concentration and aldosterone-renin ratio were significantly higher and serum potassium concentration and plasma renin activity were significantly lower in patients with unilateral hypersecretion. Plasma aldosterone concentrations after captopril challenge test, saline infusion test and rapid adrenocorticotropic hormone stimulation test were significantly higher among patients with unilateral hypersecretion. The plasma aldosterone concentration reduction ratio in saline infusion test and plasma aldosterone concentration elevation ratio during rapid adrenocorticotropic hormone stimulation test were significantly higher in patients with unilateral hypersecretion. However, areas under the curve for these parameters were not superior to the values after confirmatory tests.
Conclusions: The plasma aldosterone concentration values after captopril challenge test, saline infusion test and rapid adrenocorticotropic hormone stimulation test were useful for identifying patients with unilateral hypersecretion. However, value changes or ratios during confirmatory tests are less useful for this aim.
{"title":"Evaluation of various confirmatory tests for the diagnosis of aldosterone-producing adenoma.","authors":"Satoshi Kidoguchi, Naoki Sugano, Ruri Kawauchi, Daisuke Nakashima, Naomi Hayashi-Ishikawa, Goro Tokudome, Takashi Yokoo","doi":"10.1177/1470320320919610","DOIUrl":"https://doi.org/10.1177/1470320320919610","url":null,"abstract":"<p><strong>Introduction: </strong>Adrenal venous sampling is useful for discriminating unilateral and bilateral hypersecretion in patients with primary aldosteronism, but it is relatively invasive. To determine the site of hypersecretion more non-invasively, we evaluated predictors of unilateral hypersecretion.</p><p><strong>Materials and methods: </strong>We evaluated the baseline characteristics and the results of confirmatory tests of 123 patients with primary aldosteronism who underwent adrenal venous sampling.</p><p><strong>Results: </strong>Unilateral hypersecretion was identified in 22.0%. The plasma aldosterone concentration and aldosterone-renin ratio were significantly higher and serum potassium concentration and plasma renin activity were significantly lower in patients with unilateral hypersecretion. Plasma aldosterone concentrations after captopril challenge test, saline infusion test and rapid adrenocorticotropic hormone stimulation test were significantly higher among patients with unilateral hypersecretion. The plasma aldosterone concentration reduction ratio in saline infusion test and plasma aldosterone concentration elevation ratio during rapid adrenocorticotropic hormone stimulation test were significantly higher in patients with unilateral hypersecretion. However, areas under the curve for these parameters were not superior to the values after confirmatory tests.</p><p><strong>Conclusions: </strong>The plasma aldosterone concentration values after captopril challenge test, saline infusion test and rapid adrenocorticotropic hormone stimulation test were useful for identifying patients with unilateral hypersecretion. However, value changes or ratios during confirmatory tests are less useful for this aim.</p>","PeriodicalId":17330,"journal":{"name":"Journal of the Renin-Angiotensin-Aldosterone System","volume":"21 2","pages":"1470320320919610"},"PeriodicalIF":2.9,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1470320320919610","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37902373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-04-01DOI: 10.1177/1470320320919587
Weidong Wang, Wei Qu, Dan Sun, Xiaodan Liu
Background: The purpose of this study was to systematically evaluate the effect of renin-angiotensin-aldosterone system blockers on the incidence of contrast-induced nephropathy in patients undergoing coronary angiography or percutaneous coronary intervention.
Methods: A systematic literature search of several databases was conducted to identify studies that met the inclusion criteria. A total of 12 studies with 14 trials that performed studies on a total of 4864 patients (2484 treated with renin-angiotensin-aldosterone system blockers and 2380 in the control group) were included. The primary endpoint was the overall incidence of contrast-induced nephropathy. Analyses were performed with STATA version 12.0.
Results: The overall contrast-induced nephropathy incidence in renin-angiotensin-aldosterone system blocker and control groups was 10.43% and 6.81%, respectively. The pooled relative risk of contrast-induced nephropathy incidence was 1.22 (95% confidence interval: 0.81-1.84) in the renin-angiotensin-aldosterone system blocker group. An increased risk of developing contrast-induced nephropathy in the renin-angiotensin-aldosterone system blocker group was observed among older people, non-Asians, chronic users, and studies with larger sample size, and the pooled RRs and 95% confidence intervals were 2.02 (1.21-3.36), 2.30 (1.41-3.76), 1.69 (1.10-2.59) and 1.83 (1.28-2.63), respectively.
Conclusions: Intervention with renin-angiotensin-aldosterone system blockers was associated with an increased risk of contrast-induced nephropathy among non-Asians, chronic users, older people, and studies with larger sample size. Large clinical trials with strict inclusion criteria are needed to confirm our results and to evaluate the effect further.
{"title":"Meta-analysis of effect of renin-angiotensin-aldosterone system blockers on contrast-induced nephropathy.","authors":"Weidong Wang, Wei Qu, Dan Sun, Xiaodan Liu","doi":"10.1177/1470320320919587","DOIUrl":"https://doi.org/10.1177/1470320320919587","url":null,"abstract":"<p><strong>Background: </strong>The purpose of this study was to systematically evaluate the effect of renin-angiotensin-aldosterone system blockers on the incidence of contrast-induced nephropathy in patients undergoing coronary angiography or percutaneous coronary intervention.</p><p><strong>Methods: </strong>A systematic literature search of several databases was conducted to identify studies that met the inclusion criteria. A total of 12 studies with 14 trials that performed studies on a total of 4864 patients (2484 treated with renin-angiotensin-aldosterone system blockers and 2380 in the control group) were included. The primary endpoint was the overall incidence of contrast-induced nephropathy. Analyses were performed with STATA version 12.0.</p><p><strong>Results: </strong>The overall contrast-induced nephropathy incidence in renin-angiotensin-aldosterone system blocker and control groups was 10.43% and 6.81%, respectively. The pooled relative risk of contrast-induced nephropathy incidence was 1.22 (95% confidence interval: 0.81-1.84) in the renin-angiotensin-aldosterone system blocker group. An increased risk of developing contrast-induced nephropathy in the renin-angiotensin-aldosterone system blocker group was observed among older people, non-Asians, chronic users, and studies with larger sample size, and the pooled RRs and 95% confidence intervals were 2.02 (1.21-3.36), 2.30 (1.41-3.76), 1.69 (1.10-2.59) and 1.83 (1.28-2.63), respectively.</p><p><strong>Conclusions: </strong>Intervention with renin-angiotensin-aldosterone system blockers was associated with an increased risk of contrast-induced nephropathy among non-Asians, chronic users, older people, and studies with larger sample size. Large clinical trials with strict inclusion criteria are needed to confirm our results and to evaluate the effect further.</p>","PeriodicalId":17330,"journal":{"name":"Journal of the Renin-Angiotensin-Aldosterone System","volume":"21 2","pages":"1470320320919587"},"PeriodicalIF":2.9,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1470320320919587","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37903759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-04-01DOI: 10.1177/1470320320919635
Xiaoxue Chen, Mindan Sun
Purpose: This study aims to identify immunoglobulin-A-nephropathy-related genes based on microarray data and to investigate novel potential gene targets for immunoglobulin-A-nephropathy treatment.
Methods: Immunoglobulin-A-nephropathy chip data was obtained from the Gene Expression Omnibus database, which included 10 immunoglobulin-A-nephropathy and 22 normal samples. We used the limma package of R software to screen differentially expressed genes in immunoglobulin-A-nephropathy and normal glomerular compartment tissues. Functional enrichment (including cellular components, molecular functions, biological processes) and signal pathways were performed for the differentially expressed genes. The online analysis database (STRING) was used to construct the protein-protein interaction networks of differentially expressed genes, and Cytoscape software was used to identify the hub genes of the signal pathway. In addition, we used the Connectivity Map database to predict possible drugs for the treatment of immunoglobulin-A-nephropathy.
Results: A total of 348 differentially expressed genes were screened including 107 up-regulated and 241 down-regulated genes. Functional analysis showed that up-regulated differentially expressed genes were mainly concentrated on leukocyte migration, and the down-regulated differentially expressed genes were significantly enriched in alpha-amino acid metabolic process. A total of six hub genes were obtained: JUN, C3AR1, FN1, AGT, FOS, and SUCNR1. The small-molecule drugs thapsigargin, ciclopirox and ikarugamycin were predicted therapeutic targets against immunoglobulin-A-nephropathy.
Conclusion: Differentially expressed genes and hub genes can contribute to understanding the molecular mechanism of immunoglobulin-A-nephropathy and providing potential therapeutic targets and drugs for the diagnosis and treatment of immunoglobulin-A-nephropathy.
{"title":"Identification of key genes, pathways and potential therapeutic agents for IgA nephropathy using an integrated bioinformatics analysis.","authors":"Xiaoxue Chen, Mindan Sun","doi":"10.1177/1470320320919635","DOIUrl":"10.1177/1470320320919635","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to identify immunoglobulin-A-nephropathy-related genes based on microarray data and to investigate novel potential gene targets for immunoglobulin-A-nephropathy treatment.</p><p><strong>Methods: </strong>Immunoglobulin-A-nephropathy chip data was obtained from the Gene Expression Omnibus database, which included 10 immunoglobulin-A-nephropathy and 22 normal samples. We used the limma package of R software to screen differentially expressed genes in immunoglobulin-A-nephropathy and normal glomerular compartment tissues. Functional enrichment (including cellular components, molecular functions, biological processes) and signal pathways were performed for the differentially expressed genes. The online analysis database (STRING) was used to construct the protein-protein interaction networks of differentially expressed genes, and Cytoscape software was used to identify the hub genes of the signal pathway. In addition, we used the Connectivity Map database to predict possible drugs for the treatment of immunoglobulin-A-nephropathy.</p><p><strong>Results: </strong>A total of 348 differentially expressed genes were screened including 107 up-regulated and 241 down-regulated genes. Functional analysis showed that up-regulated differentially expressed genes were mainly concentrated on leukocyte migration, and the down-regulated differentially expressed genes were significantly enriched in alpha-amino acid metabolic process. A total of six hub genes were obtained: JUN, C3AR1, FN1, AGT, FOS, and SUCNR1. The small-molecule drugs thapsigargin, ciclopirox and ikarugamycin were predicted therapeutic targets against immunoglobulin-A-nephropathy.</p><p><strong>Conclusion: </strong>Differentially expressed genes and hub genes can contribute to understanding the molecular mechanism of immunoglobulin-A-nephropathy and providing potential therapeutic targets and drugs for the diagnosis and treatment of immunoglobulin-A-nephropathy.</p>","PeriodicalId":17330,"journal":{"name":"Journal of the Renin-Angiotensin-Aldosterone System","volume":"21 2","pages":"1470320320919635"},"PeriodicalIF":2.9,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/df/a5/10.1177_1470320320919635.PMC7227159.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37902376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-04-01DOI: 10.1177/1470320320926899
Raymond Pranata, Michael Anthonius Lim, Ian Huang, Sunu Budhi Raharjo, Antonia Anna Lukito
Objective: To investigate the association between hypertension and outcome in patients with Coronavirus Disease 2019 (COVID-19) pneumonia.
Methods: We performed a systematic literature search from several databases on studies that assess hypertension and outcome in COVID-19. Composite of poor outcome, comprising of mortality, severe COVID-19, acute respiratory distress syndrome (ARDS), need for intensive care unit (ICU) care and disease progression were the outcomes of interest.
Results: A total of 6560 patients were pooled from 30 studies. Hypertension was associated with increased composite poor outcome (risk ratio (RR) 2.11 (95% confidence interval (CI) 1.85, 2.40), p < 0.001; I2, 44%) and its sub-group, including mortality (RR 2.21 (1.74, 2.81), p < 0.001; I2, 66%), severe COVID-19 (RR 2.04 (1.69, 2.47), p < 0.001; I2 31%), ARDS (RR 1.64 (1.11, 2.43), p = 0.01; I2,0%, p = 0.35), ICU care (RR 2.11 (1.34, 3.33), p = 0.001; I2 18%, p = 0.30), and disease progression (RR 3.01 (1.51, 5.99), p = 0.002; I2 0%, p = 0.55). Meta-regression analysis showed that gender (p = 0.013) was a covariate that affects the association. The association was stronger in studies with a percentage of males < 55% compared to ⩾ 55% (RR 2.32 v. RR 1.79).
Conclusion: Hypertension was associated with increased composite poor outcome, including mortality, severe COVID-19, ARDS, need for ICU care and disease progression in patients with COVID-19.
{"title":"Hypertension is associated with increased mortality and severity of disease in COVID-19 pneumonia: A systematic review, meta-analysis and meta-regression.","authors":"Raymond Pranata, Michael Anthonius Lim, Ian Huang, Sunu Budhi Raharjo, Antonia Anna Lukito","doi":"10.1177/1470320320926899","DOIUrl":"10.1177/1470320320926899","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the association between hypertension and outcome in patients with Coronavirus Disease 2019 (COVID-19) pneumonia.</p><p><strong>Methods: </strong>We performed a systematic literature search from several databases on studies that assess hypertension and outcome in COVID-19. Composite of poor outcome, comprising of mortality, severe COVID-19, acute respiratory distress syndrome (ARDS), need for intensive care unit (ICU) care and disease progression were the outcomes of interest.</p><p><strong>Results: </strong>A total of 6560 patients were pooled from 30 studies. Hypertension was associated with increased composite poor outcome (risk ratio (RR) 2.11 (95% confidence interval (CI) 1.85, 2.40), <i>p</i> < 0.001; <i>I</i><sup>2</sup>, 44%) and its sub-group, including mortality (RR 2.21 (1.74, 2.81), <i>p</i> < 0.001; <i>I</i><sup>2</sup>, 66%), severe COVID-19 (RR 2.04 (1.69, 2.47), <i>p</i> < 0.001; <i>I</i><sup>2</sup> 31%), ARDS (RR 1.64 (1.11, 2.43), <i>p</i> = 0.01; <i>I</i><sup>2</sup>,0%, <i>p</i> = 0.35), ICU care (RR 2.11 (1.34, 3.33), <i>p</i> = 0.001; <i>I</i><sup>2</sup> 18%, <i>p</i> = 0.30), and disease progression (RR 3.01 (1.51, 5.99), <i>p</i> = 0.002; <i>I</i><sup>2</sup> 0%, <i>p</i> = 0.55). Meta-regression analysis showed that gender (<i>p</i> = 0.013) was a covariate that affects the association. The association was stronger in studies with a percentage of males < 55% compared to ⩾ 55% (RR 2.32 v. RR 1.79).</p><p><strong>Conclusion: </strong>Hypertension was associated with increased composite poor outcome, including mortality, severe COVID-19, ARDS, need for ICU care and disease progression in patients with COVID-19.</p>","PeriodicalId":17330,"journal":{"name":"Journal of the Renin-Angiotensin-Aldosterone System","volume":"21 2","pages":"1470320320926899"},"PeriodicalIF":2.1,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/75/bb/10.1177_1470320320926899.PMC7231906.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37935308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-04-01DOI: 10.1177/1470320320928872
Can Turk, Seyhan Turk, Elif Sena Temirci, Umit Yavuz Malkan, İbrahim C Haznedaroglu
Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently identified coronavirus family member that triggers a respiratory disease similar to severe acute respiratory syndrome coronavirus (SARS-CoV). SARS-CoV and SARS-CoV-2 are very similar to each other in many respects, such as structure, genetics, and pathobiology. We hypothesized that coronaviruses could affect pulmonary tissues via integration with the critical immune genes after their interaction with renin-angiotensin system (RAS) elements. The aim of the present bioinformatics study was to assess expression changes of the RAS and non-RAS genes, particularly immune response genes, in the lung epithelial cells after infection with SARS-CoV.
Methods: Linear regression, hierarchical clustering, pathway analysis, and network analysis were performed using the E-GEOD-17400 data set.
Results: The whole-genome expression data of the lung epithelial cells infected with SARS-CoV for 12, 24, and 48 hours were analyzed, and a total of 15 RAS family and 29 immune genes were found to be highly correlated with the exposure time to the virus in the studied groups.
Conclusion: RAS genes are important at the initiation of the infections caused by coronavirus family members and may have a strong relationship with the exchange of immune genes in due course following the infection.
{"title":"In vitro analysis of the renin-angiotensin system and inflammatory gene transcripts in human bronchial epithelial cells after infection with severe acute respiratory syndrome coronavirus.","authors":"Can Turk, Seyhan Turk, Elif Sena Temirci, Umit Yavuz Malkan, İbrahim C Haznedaroglu","doi":"10.1177/1470320320928872","DOIUrl":"10.1177/1470320320928872","url":null,"abstract":"<p><strong>Introduction: </strong>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently identified coronavirus family member that triggers a respiratory disease similar to severe acute respiratory syndrome coronavirus (SARS-CoV). SARS-CoV and SARS-CoV-2 are very similar to each other in many respects, such as structure, genetics, and pathobiology. We hypothesized that coronaviruses could affect pulmonary tissues via integration with the critical immune genes after their interaction with renin-angiotensin system (RAS) elements. The aim of the present bioinformatics study was to assess expression changes of the RAS and non-RAS genes, particularly immune response genes, in the lung epithelial cells after infection with SARS-CoV.</p><p><strong>Methods: </strong>Linear regression, hierarchical clustering, pathway analysis, and network analysis were performed using the E-GEOD-17400 data set.</p><p><strong>Results: </strong>The whole-genome expression data of the lung epithelial cells infected with SARS-CoV for 12, 24, and 48 hours were analyzed, and a total of 15 RAS family and 29 immune genes were found to be highly correlated with the exposure time to the virus in the studied groups.</p><p><strong>Conclusion: </strong>RAS genes are important at the initiation of the infections caused by coronavirus family members and may have a strong relationship with the exchange of immune genes in due course following the infection.</p>","PeriodicalId":17330,"journal":{"name":"Journal of the Renin-Angiotensin-Aldosterone System","volume":"21 2","pages":"1470320320928872"},"PeriodicalIF":2.9,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1470320320928872","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38004286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-04-01DOI: 10.1177/1470320320926911
Peter Sever, Sebastian L Johnston
Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). The renin-angiotensin-aldosterone system (RAAS) has been the focus of research for decades because of its critical role in the physiology of the circulation and the pathophysiology of cardiovascular disease. However, it plays an important role in regulating multiple organs and functions in other tissues including the lung, kidney and heart, together with involvement in the inflammatory response. Early research identified angiotensin-converting enzyme (ACE), a protease which cleaves angiotensin (Ang) I to produce Ang II, the key effector peptide of the RAAS. However, in 2000, a second ACE, ACE2, was discovered which primarily metabolises Ang II into Ang-(1–9). Ang-(1–9) is subsequently converted by neutral endopeptidase and ACE to Ang-(1–7), a vasodilatory peptide. Extensive investigations of ACE2 have revealed that it is widely distributed primarily on lung alveolar epithelial cells, small intestinal enterocytes and vascular endothelial cells in many organs including liver, kidney and brain,1 with multiple additional actions including antiproliferative and antifibrotic effects and, more recently, a role of viral receptor and amino acid transporter.2 Studies with coronaviruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus showed that these viruses relied on a viral spike protein to bind host cell surface receptors for entry into cells. SARS-CoV and SARSCoV-2 both encode similar large-spike proteins with 76% sequence identity. Molecular modelling has shown structural similarity between the receptor binding domains of SARS-CoV and SARS-CoV-2 despite amino acid mutations of the SARS-CoV-2 receptor binding domain.3 It has now been demonstrated that the receptor binding domain in the spike protein interacts with high affinity with ACE2.4–6 By analogy with the SARS virus, SARS-CoV-2 will downregulate cellular expression of ACE2, resulting from endocytosis of the ACE2-SARS-CoV-2 complex, which is essential for infection, activation of ADAM metallopeptidase domain 17, a coregulator of ACE2, and shedding of ACE2 from the cell membrane (Figure 1). Novel antibodies and therapeutic peptides are being developed to interact with the SARS-CoV-2 receptor binding domain and block its interaction with ACE2. An alternative approach is the use of peptides derived from SARS-CoV-2 and ACE2. Interestingly, a peptide composed of two ACE2 motifs (aa22-44 and 351-357) linked by glycine exhibited potent anti-SARS activity.7 Other targets to control viral replication incl
{"title":"The Renin-Angiotensin system and SARS-CoV-2 infection: A role for the ACE2 receptor?","authors":"Peter Sever, Sebastian L Johnston","doi":"10.1177/1470320320926911","DOIUrl":"https://doi.org/10.1177/1470320320926911","url":null,"abstract":"Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). The renin-angiotensin-aldosterone system (RAAS) has been the focus of research for decades because of its critical role in the physiology of the circulation and the pathophysiology of cardiovascular disease. However, it plays an important role in regulating multiple organs and functions in other tissues including the lung, kidney and heart, together with involvement in the inflammatory response. Early research identified angiotensin-converting enzyme (ACE), a protease which cleaves angiotensin (Ang) I to produce Ang II, the key effector peptide of the RAAS. However, in 2000, a second ACE, ACE2, was discovered which primarily metabolises Ang II into Ang-(1–9). Ang-(1–9) is subsequently converted by neutral endopeptidase and ACE to Ang-(1–7), a vasodilatory peptide. Extensive investigations of ACE2 have revealed that it is widely distributed primarily on lung alveolar epithelial cells, small intestinal enterocytes and vascular endothelial cells in many organs including liver, kidney and brain,1 with multiple additional actions including antiproliferative and antifibrotic effects and, more recently, a role of viral receptor and amino acid transporter.2 Studies with coronaviruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus showed that these viruses relied on a viral spike protein to bind host cell surface receptors for entry into cells. SARS-CoV and SARSCoV-2 both encode similar large-spike proteins with 76% sequence identity. Molecular modelling has shown structural similarity between the receptor binding domains of SARS-CoV and SARS-CoV-2 despite amino acid mutations of the SARS-CoV-2 receptor binding domain.3 It has now been demonstrated that the receptor binding domain in the spike protein interacts with high affinity with ACE2.4–6 By analogy with the SARS virus, SARS-CoV-2 will downregulate cellular expression of ACE2, resulting from endocytosis of the ACE2-SARS-CoV-2 complex, which is essential for infection, activation of ADAM metallopeptidase domain 17, a coregulator of ACE2, and shedding of ACE2 from the cell membrane (Figure 1). Novel antibodies and therapeutic peptides are being developed to interact with the SARS-CoV-2 receptor binding domain and block its interaction with ACE2. An alternative approach is the use of peptides derived from SARS-CoV-2 and ACE2. Interestingly, a peptide composed of two ACE2 motifs (aa22-44 and 351-357) linked by glycine exhibited potent anti-SARS activity.7 Other targets to control viral replication incl","PeriodicalId":17330,"journal":{"name":"Journal of the Renin-Angiotensin-Aldosterone System","volume":"21 2","pages":"1470320320926911"},"PeriodicalIF":2.9,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1470320320926911","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37931290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: This study aimed to investigate the effect of anti-osteoporosis therapy on plasma aldosterone concentration (PAC), plasma renin concentration (PRC) and the aldosterone/renin ratio (ARR) in patients with postmenopausal osteoporosis.
Methods: In 60 patients with postmenopausal osteoporosis, bone mineral density (BMD), PAC and PRC were measured before and after treatment with alendronate (70 mg/week, n=22) or recombinant human parathyroid hormone (20 μg/day, n=35) for 48 weeks.
Results: PAC was negatively correlated with the T-score of lumbar spine BMD and femoral neck BMD (lumbar r=-0.386, p<0.01; femoral neck r=-0.262, p<0.05). With the improvement in lumbar BMD after anti-osteoporosis treatment (T-score -3.4±0.5 vs. -3.1 ±0.4, p<0.0001), PAC decreased from 182.8±53.2 to 143.7±68.6 pg/mL (p<0.0001), PRC increased from 7.8±11.6 to 39.2±50.0 μIU/mL (p<0.0001) and the ARR decreased from 74.8±75.2 to 13.1±17.1 pg/μIU (p<0.0001). At baseline, 58% (35/60) of the patients had an ARR >37 pg/μIU, and the proportion decreased to 8% (5/57) after treatment.
Conclusion: Treatment with alendronate or parathyroid hormone causes decreased PAC and increased PRC, resulting in a decreased ARR in postmenopausal women with osteoporosis.
{"title":"Effects of anti-osteoporosis therapy on plasma aldosterone and renin.","authors":"Qingfen Hu, Kangla Liao, Longwei Zhang, Xiaoyu Shu, Zhixin Xu, Yuyang Qiu, Qifu Li, Shumin Yang","doi":"10.1177/1470320320928874","DOIUrl":"https://doi.org/10.1177/1470320320928874","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the effect of anti-osteoporosis therapy on plasma aldosterone concentration (PAC), plasma renin concentration (PRC) and the aldosterone/renin ratio (ARR) in patients with postmenopausal osteoporosis.</p><p><strong>Methods: </strong>In 60 patients with postmenopausal osteoporosis, bone mineral density (BMD), PAC and PRC were measured before and after treatment with alendronate (70 mg/week, <i>n</i>=22) or recombinant human parathyroid hormone (20 μg/day, <i>n</i>=35) for 48 weeks.</p><p><strong>Results: </strong>PAC was negatively correlated with the T-score of lumbar spine BMD and femoral neck BMD (lumbar <i>r</i>=-0.386, <i>p</i><0.01; femoral neck <i>r</i>=-0.262, <i>p</i><0.05). With the improvement in lumbar BMD after anti-osteoporosis treatment (T-score -3.4±0.5 vs. -3.1 ±0.4, <i>p</i><0.0001), PAC decreased from 182.8±53.2 to 143.7±68.6 pg/mL (<i>p</i><0.0001), PRC increased from 7.8±11.6 to 39.2±50.0 μIU/mL (<i>p</i><0.0001) and the ARR decreased from 74.8±75.2 to 13.1±17.1 pg/μIU (<i>p</i><0.0001). At baseline, 58% (35/60) of the patients had an ARR >37 pg/μIU, and the proportion decreased to 8% (5/57) after treatment.</p><p><strong>Conclusion: </strong>Treatment with alendronate or parathyroid hormone causes decreased PAC and increased PRC, resulting in a decreased ARR in postmenopausal women with osteoporosis.</p>","PeriodicalId":17330,"journal":{"name":"Journal of the Renin-Angiotensin-Aldosterone System","volume":"21 2","pages":"1470320320928874"},"PeriodicalIF":2.9,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1470320320928874","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37996741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-04-01DOI: 10.1177/1470320319900038
Jazmín Flores-Monroy, Diego Lezama-Martínez, Salvador Fonseca-Coronado, Luisa Martínez-Aguilar
Background: There is some evidence that components of the renin-angiotensin system and kallikrein-kinin system are not similarly regulated in both sexes. The aim of this work was to analyze the expression of angiotensin-converting enzyme, angiotensin-converting enzyme 2, angiotensin 1 receptor, angiotensin 2 receptor, beta-1 receptor, and beta-2 receptor during the evolution of myocardial infarction.
Methods: Thirty-six male and 36 female Wistar rats were used. Myocardial infarction was induced. Six groups of both sexes were formed, (n=6): (a) sham; (b) 48 h myocardial infarction; (c) one week myocardial infarction; (d) two weeks myocardial infarction; (e) three weeks myocardial infarction and (f) four weeks myocardial infarction. The expression was evaluated by real-time polymerase chain reaction on the penumbra of left ventricle.
Results: The mRNA expression of most biomarkers was lower in females than in males. During acute infarction, an increase of all protein expression was found in female and at two weeks while in the male only biomarker changes occurred at three weeks. In addition, in male biomarkers mRNA expression decreased during chronic infarction while in females it did not.
Conclusions: The renin-angiotensin system and kallikrein-kinin system biomarkers expression occurs at earlier times in the female than in the male rat. In addition, during chronic myocardial infarction these biomarkers remained unchanged in females while in males they decreased.
{"title":"Differences in the expression of the renin angiotensin system and the kallikrein-kinin system during the course of myocardial infarction in male and female Wistar rats.","authors":"Jazmín Flores-Monroy, Diego Lezama-Martínez, Salvador Fonseca-Coronado, Luisa Martínez-Aguilar","doi":"10.1177/1470320319900038","DOIUrl":"https://doi.org/10.1177/1470320319900038","url":null,"abstract":"<p><strong>Background: </strong>There is some evidence that components of the renin-angiotensin system and kallikrein-kinin system are not similarly regulated in both sexes. The aim of this work was to analyze the expression of angiotensin-converting enzyme, angiotensin-converting enzyme 2, angiotensin 1 receptor, angiotensin 2 receptor, beta-1 receptor, and beta-2 receptor during the evolution of myocardial infarction.</p><p><strong>Methods: </strong>Thirty-six male and 36 female Wistar rats were used. Myocardial infarction was induced. Six groups of both sexes were formed, (<i>n</i>=6): (a) sham; (b) 48 h myocardial infarction; (c) one week myocardial infarction; (d) two weeks myocardial infarction; (e) three weeks myocardial infarction and (f) four weeks myocardial infarction. The expression was evaluated by real-time polymerase chain reaction on the penumbra of left ventricle.</p><p><strong>Results: </strong>The mRNA expression of most biomarkers was lower in females than in males. During acute infarction, an increase of all protein expression was found in female and at two weeks while in the male only biomarker changes occurred at three weeks. In addition, in male biomarkers mRNA expression decreased during chronic infarction while in females it did not.</p><p><strong>Conclusions: </strong>The renin-angiotensin system and kallikrein-kinin system biomarkers expression occurs at earlier times in the female than in the male rat. In addition, during chronic myocardial infarction these biomarkers remained unchanged in females while in males they decreased.</p>","PeriodicalId":17330,"journal":{"name":"Journal of the Renin-Angiotensin-Aldosterone System","volume":"21 2","pages":"1470320319900038"},"PeriodicalIF":2.9,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1470320319900038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37978204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}