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Association of angiotensin-converting enzyme gene insertion/deletion polymorphism and obstructive sleep apnoea in a Chinese population: A meta-analysis. 中国人群中血管紧张素转换酶基因插入/缺失多态性与阻塞性睡眠呼吸暂停的关联:一项荟萃分析
IF 2.9 4区 医学 Q3 PERIPHERAL VASCULAR DISEASE Pub Date : 2020-06-17 eCollection Date: 2020-04-01 DOI: 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。
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引用次数: 1
Significance of the Renin-Angiotensin System in Clinical Conditions 肾素-血管紧张素系统在临床中的意义
IF 2.9 4区 医学 Q3 PERIPHERAL VASCULAR DISEASE Pub Date : 2020-05-16 DOI: 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.
肾素-血管紧张素系统在其循环和局部组织中的作用,与多种其他组织和器官系统中的调节和信号机制交织在一起。它在动脉血压的正常调节和高血压的发展中起着核心作用,高血压是一个巨大的全球公共卫生负担,也是心血管疾病发展中一个关键的可改变风险因素。肾素-血管紧张素系统在一系列其他临床疾病中也起着重要作用,如心力衰竭、肾衰竭、糖尿病等。肾素-血管紧张素系统的治疗干预包括血管紧张素转换酶抑制剂和血管紧张素受体拮抗剂等药物的使用,这些药物在多年的实际使用中已经建立起来,并且作为临床有效的工具是无价的。此外,许多其他针对肾素-血管紧张素系统成分的治疗方法已经开发或正在开发中。本章将详细讨论该系统在最相关的临床条件下的作用。
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引用次数: 4
Evaluation of various confirmatory tests for the diagnosis of aldosterone-producing adenoma. 醛固酮产生性腺瘤诊断的各种确证试验的评价。
IF 2.9 4区 医学 Q3 PERIPHERAL VASCULAR DISEASE Pub Date : 2020-04-01 DOI: 10.1177/1470320320919610
Satoshi Kidoguchi, Naoki Sugano, Ruri Kawauchi, Daisuke Nakashima, Naomi Hayashi-Ishikawa, Goro Tokudome, Takashi Yokoo

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.

肾上腺静脉取样对于鉴别原发性醛固酮增多症患者的单侧和双侧高分泌是有用的,但它是相对侵入性的。为了更无创地确定高分泌部位,我们评估了单侧高分泌的预测因素。材料和方法:我们评估了123例接受肾上腺静脉取样的原发性醛固酮增多症患者的基线特征和确认试验的结果。结果:单侧分泌亢进占22.0%。单侧高分泌患者血浆醛固酮浓度及醛固酮-肾素比值显著升高,血钾浓度及血浆肾素活性显著降低。单侧高分泌患者在卡托普利激发试验、生理盐水输注试验和促肾上腺皮质激素快速刺激试验后血浆醛固酮浓度显著升高。单侧高分泌患者生理盐水输注试验时血浆醛固酮浓度降低率和促肾上腺皮质激素快速刺激试验时血浆醛固酮浓度升高率均显著升高。然而,这些参数的曲线下面积并不优于验证试验后的值。结论:卡托普利激发试验、生理盐水输注试验和促肾上腺皮质激素快速刺激试验后的血浆醛固酮浓度值可用于单侧高分泌患者的鉴别。然而,在确认性测试期间,值的变化或比率对这一目的的用处不大。
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引用次数: 3
Meta-analysis of effect of renin-angiotensin-aldosterone system blockers on contrast-induced nephropathy. 肾素-血管紧张素-醛固酮系统阻滞剂对造影剂肾病疗效的meta分析。
IF 2.9 4区 医学 Q3 PERIPHERAL VASCULAR DISEASE Pub Date : 2020-04-01 DOI: 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.

背景:本研究的目的是系统评价肾素-血管紧张素-醛固酮系统阻滞剂对冠脉造影或经皮冠状动脉介入治疗患者造影剂肾病发生率的影响。方法:对多个数据库进行系统的文献检索,以确定符合纳入标准的研究。共纳入了12项研究,14项试验,共对4864名患者进行了研究(2484名患者接受肾素-血管紧张素-醛固酮系统阻滞剂治疗,2380名患者为对照组)。主要终点是造影剂肾病的总发病率。使用STATA 12.0版本进行分析。结果:肾素-血管紧张素-醛固酮系统阻滞剂组和对照组造影剂肾病总发生率分别为10.43%和6.81%。在肾素-血管紧张素-醛固酮系统阻滞剂组,对比剂肾病发生率的总相对危险度为1.22(95%可信区间:0.81-1.84)。在老年人、非亚洲人、慢性使用者和样本量较大的研究中,肾素-血管紧张素-醛固酮系统阻滞剂组发生对比剂肾病的风险增加,合并rr和95%置信区间分别为2.02(1.21-3.36)、2.30(1.41-3.76)、1.69(1.10-2.59)和1.83(1.28-2.63)。结论:肾素-血管紧张素-醛固酮系统阻滞剂干预与非亚洲人、慢性使用者、老年人和样本量较大的研究中造影剂肾病的风险增加相关。需要有严格纳入标准的大型临床试验来证实我们的结果并进一步评估效果。
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引用次数: 5
Identification of key genes, pathways and potential therapeutic agents for IgA nephropathy using an integrated bioinformatics analysis. 利用综合生物信息学分析鉴定 IgA 肾病的关键基因、通路和潜在治疗药物。
IF 2.9 4区 医学 Q3 PERIPHERAL VASCULAR DISEASE Pub Date : 2020-04-01 DOI: 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.

目的:本研究旨在根据芯片数据确定免疫球蛋白-A-肾病相关基因,并研究治疗免疫球蛋白-A-肾病的潜在新基因靶点:免疫球蛋白-A肾病芯片数据来自基因表达总库数据库,其中包括10个免疫球蛋白-A肾病样本和22个正常样本。我们使用 R 软件的 limma 软件包筛选免疫球蛋白-A 肾病和正常肾小球区组织中的差异表达基因。我们对差异表达基因进行了功能富集(包括细胞成分、分子功能、生物过程)和信号通路分析。在线分析数据库(STRING)用于构建差异表达基因的蛋白-蛋白相互作用网络,Cytoscape软件用于识别信号通路的枢纽基因。此外,我们还利用 Connectivity Map 数据库预测了治疗免疫球蛋白-A 肾病的可能药物:结果:共筛选出348个差异表达基因,包括107个上调基因和241个下调基因。功能分析显示,上调差异表达基因主要集中在白细胞迁移方面,而下调差异表达基因则显著富集在α-氨基酸代谢过程中。共获得 6 个中枢基因:JUN、C3AR1、FN1、AGT、FOS 和 SUCNR1。小分子药物thapsigargin、ciclopirox和ikarugamycin被预测为免疫球蛋白-A肾病的治疗靶点:结论:差异表达基因和枢纽基因有助于了解免疫球蛋白-A肾病的分子机制,并为免疫球蛋白-A肾病的诊断和治疗提供潜在的治疗靶点和药物。
{"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}
引用次数: 0
Hypertension is associated with increased mortality and severity of disease in COVID-19 pneumonia: A systematic review, meta-analysis and meta-regression. 高血压与 COVID-19 肺炎死亡率和病情严重程度的增加有关:系统回顾、荟萃分析和荟萃回归。
IF 2.1 4区 医学 Q3 PERIPHERAL VASCULAR DISEASE Pub Date : 2020-04-01 DOI: 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.

目的研究冠状病毒病 2019(COVID-19)肺炎患者的高血压与预后之间的关系:我们在多个数据库中对评估 COVID-19 患者高血压和预后的研究进行了系统性文献检索。包括死亡率、重症 COVID-19、急性呼吸窘迫综合征(ARDS)、重症监护室(ICU)护理需求和疾病进展在内的综合不良预后是我们关注的结果:结果:共汇总了 30 项研究中的 6560 名患者。高血压与综合不良预后增加有关(风险比 (RR) 2.11 (95% 置信区间 (CI) 1.85, 2.40),P < 0.001; I2, 44%),其亚组包括死亡率 (RR 2.21 (1.74, 2.81),P < 0.001; I2, 66%)、严重 COVID-19 (RR 2. 04 (1.69, 2.81),P < 0.001; I2, 44%)。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 护理 (RR 2.11 (1.34, 3.33), p = 0.001; I2 18%, p = 0.30), 和疾病进展 (RR 3.01 (1.51, 5.99), p = 0.002; I2 0%, p = 0.55)。元回归分析表明,性别(p = 0.013)是影响相关性的协变量。男性比例小于 55% 的研究与 ⩾ 55% 的研究相比,关联性更强(RR 2.32 v. RR 1.79):高血压与COVID-19患者的综合不良预后增加有关,包括死亡率、严重COVID-19、ARDS、ICU护理需求和疾病进展。
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引用次数: 0
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. 冠状病毒感染后人支气管上皮细胞肾素-血管紧张素系统及炎症基因转录物的体外分析
IF 2.9 4区 医学 Q3 PERIPHERAL VASCULAR DISEASE Pub Date : 2020-04-01 DOI: 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.

简介:严重急性呼吸综合征冠状病毒2 (SARS-CoV-2)是一种新发现的冠状病毒家族成员,可引发类似于严重急性呼吸综合征冠状病毒(SARS-CoV)的呼吸道疾病。SARS-CoV和SARS-CoV-2在结构、遗传学和病理生物学等许多方面非常相似。我们假设冠状病毒在与肾素-血管紧张素系统(RAS)元件相互作用后,通过与关键免疫基因的整合影响肺组织。本生物信息学研究的目的是评估感染sars冠状病毒后肺上皮细胞中RAS和非RAS基因,特别是免疫反应基因的表达变化。方法:采用E-GEOD-17400数据集进行线性回归、层次聚类、路径分析和网络分析。结果:对感染SARS-CoV 12、24和48 h肺上皮细胞全基因组表达数据进行分析,发现实验组中有15个RAS家族和29个免疫基因与病毒暴露时间高度相关。结论:RAS基因在冠状病毒感染开始时起重要作用,并可能与感染后适当的免疫基因交换有密切关系。
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引用次数: 14
The Renin-Angiotensin system and SARS-CoV-2 infection: A role for the ACE2 receptor? 肾素-血管紧张素系统与SARS-CoV-2感染:ACE2受体的作用?
IF 2.9 4区 医学 Q3 PERIPHERAL VASCULAR DISEASE Pub Date : 2020-04-01 DOI: 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,&nbsp;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}
引用次数: 3
Effects of anti-osteoporosis therapy on plasma aldosterone and renin. 抗骨质疏松治疗对血浆醛固酮和肾素的影响。
IF 2.9 4区 医学 Q3 PERIPHERAL VASCULAR DISEASE Pub Date : 2020-04-01 DOI: 10.1177/1470320320928874
Qingfen Hu, Kangla Liao, Longwei Zhang, Xiaoyu Shu, Zhixin Xu, Yuyang Qiu, Qifu Li, Shumin Yang

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.

目的:探讨抗骨质疏松治疗对绝经后骨质疏松患者血浆醛固酮浓度(PAC)、血浆肾素浓度(PRC)及醛固酮/肾素比值(ARR)的影响。方法:对60例绝经后骨质疏松患者分别给予阿仑膦酸钠(70 mg/周,n=22)或重组人甲状旁腺激素(20 μg/天,n=35)治疗48周前后,测定骨密度(BMD)、PAC、PRC。结果:PAC与腰椎骨密度t评分、股骨颈骨密度t评分呈负相关(腰椎r=-0.386, pr=-0.262, ppppp37 pg/μIU),治疗后比例降至8%(5/57)。结论:阿仑膦酸钠或甲状旁腺激素治疗可降低绝经后骨质疏松妇女的PAC,增加PRC,从而降低ARR。
{"title":"Effects of anti-osteoporosis therapy on plasma aldosterone and renin.","authors":"Qingfen Hu,&nbsp;Kangla Liao,&nbsp;Longwei Zhang,&nbsp;Xiaoyu Shu,&nbsp;Zhixin Xu,&nbsp;Yuyang Qiu,&nbsp;Qifu Li,&nbsp;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}
引用次数: 1
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. 雄性和雌性Wistar大鼠心肌梗死过程中肾素-血管紧张素系统和钾化钾-激肽系统表达的差异。
IF 2.9 4区 医学 Q3 PERIPHERAL VASCULAR DISEASE Pub Date : 2020-04-01 DOI: 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.

背景:有一些证据表明肾素-血管紧张素系统和钾化钾素-激肽系统的成分在两性中没有相似的调节。分析血管紧张素转换酶、血管紧张素转换酶2、血管紧张素1受体、血管紧张素2受体、β -1受体和β -2受体在心肌梗死演变过程中的表达。方法:雄性Wistar大鼠36只,雌性Wistar大鼠36只。诱导心肌梗死。男女共分为六组(n=6):(a)假手术;(b) 48 h心肌梗死;(c) 1周心肌梗死;(d) 2周心肌梗死;(e) 3周心肌梗死;(f) 4周心肌梗死。采用实时聚合酶链反应在左心室半暗区检测其表达。结果:大多数生物标志物的mRNA表达在女性中低于男性。在急性梗死期间,在女性和两周时发现所有蛋白质表达增加,而在男性中,只有生物标志物在三周时发生变化。此外,男性生物标志物mRNA表达在慢性梗死期间下降,而女性则没有。结论:雌性大鼠肾素-血管紧张素系统和钾化钾素-激肽系统生物标志物的表达早于雄性大鼠。此外,在慢性心肌梗死期间,这些生物标志物在女性中保持不变,而在男性中则有所下降。
{"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,&nbsp;Diego Lezama-Martínez,&nbsp;Salvador Fonseca-Coronado,&nbsp;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}
引用次数: 2
期刊
Journal of the Renin-Angiotensin-Aldosterone System
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