Extracellular vesicles and angiotensin-converting enzyme 2 in COVID-19 disease

Extracellular vesicles(EVs)are membranous vesicular structures released from almost all eukaryotic cell types under different physiological or pathological conditions.Growing evidence demonstrates that EVs can serve as mediators of intercellular communication between donor and recipient cells or microorganism-infected and noninfected cells.Coronavirus disease 2019(COVID-19)disease is caused by infection of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)of host cells in the respiratory system and various extra-pulmonary tissue/organs,resulting in complications of multiple organ systems.As the cell surface receptor,angiotensin-converting enzyme 2(ACE2)mediates cellular entry of SARS-CoV-2 into the host cells in patients with COVID-19.Recent studies have found that ACE2 can be released with EVs,which have been shown to interfere with the entry of the virus into host cells and thus may be involved in COVID-19 pathophysiology.In addition,ACE2,neprilysin(NEP),and thimet oligopeptidase(TOP)are the key enzymes that regulate angiotensin metabolism by converting angiotensin II or angiotensin I to angiotensin 1-7,the latter of which has protective effects in counterbalancing the harmful effects of angiotensin II in COVID-19 disease.This review summarizes the recent research progress regarding EV-associated ACE2,NEP,and TOP and the perspectives of their potential involvement in the pathophysiology of COVID-19 disease.

Expression of Extracellular Signal-regulated Kinase and Angiotensin-converting Enzyme in Human Atria during Atrial Fibrillation

In order to investigate the changes in the expression of extracellular signal regulated kinase (ERK1/ERK2) and angiotensin converting enzyme (ACE) in the patients with atrial fibrillation (AF), 52 patients with rheumatic heart diseases were examined. Nineteen patients had chronic persistent AF (AF≥6 months, CAF), 12 patients had paroxymal AF (PAF) and 21 patients had no history of AF. The ERK expression was detected at the mRNA level by reverse transcription polymerase chain reaction, at the protein level by Western blotting and at atrial tissue level by immunohistochemistry. ERK activating kinases (MEK1/2) and ACE were determined by Western blotting techniques. The expression of ERK2 mRNA was increased in the patients with CAF (74±19 U vs sinus rhythm: 32±24 U, P <0.05). Activated ERK1/ERK2 and MEK1/2 were increased to more than 150 % in the patients with AF compared to those with sinus rhythm. No significant difference between CAF and PAF was found. The expression of ACE was three fold increased in the patients with CAF compared to those with sinus rhythm. Patients with AF showed an increased expression of ERK1/ERK2 in atrial interstitial cells and marked atrial fibrosis. An ACE dependent increase in the amounts of activated ERK1/ERK2 in atrial interstitial cells may be one of molecular mechanisms for the development of atrial fibrosis in the patients with AF. These findings may have important impact on the treatment of AF.

Purification and Molecular Docking Study of Angiotensin-I Converting Enzyme (ACE) Inhibitory Peptide from Alcalase Hydrolysate of Hazelnut (<i>Corylus heterophylla</i>Fisch) Protein

Although a number of bioactive peptides are capable of angiotensin I-converting enzyme (ACE) inhibitory effects, little is known regarding the mechanism of hazelnut peptides using molecular simulation. In the present study, gel filtration chromatography, reverse phase-high performance liquid chromatography, and liquid chromatography-electrospray ionization-tandem mass (LC-ESI-MS/MS) were employed for purifying and identifying the ACE inhibitory peptides from hazelnut. To understand the mode of action of these peptides, the interaction between the inhibitory peptides and ACE was investigated. The results identified novel ACE inhibitory peptides Asp-Asp-Glu-Leu-Arg-Gln-Ala (DDELRQA), Asp-Asp-Glu-Leu-Arg-Ala-Ala (DDELRAA), and Asp-Gly-Glu-Leu-Arg-Glu (DGELRE). The binding free energies of DDELRQA, DDELRAA, and DGELRE for ACE were -10.2, -9.0, and -8.8 kcal/mol, respectively. This study proves the high stability of ACE inhibitory peptides derived from hazelnut against different temperature and pH of processing.

注意缺陷多动障碍患儿血清ACE2,TWEAK和CCL5水平检测及诊断价值研究

目的 探究血清血管紧张素转换酶2(angiotensin-converting enzyme 2,ACE2),细胞因子肿瘤坏死因子样细胞凋亡弱诱导因子(tumor necrosis factor-like weak inducer of apoptosis,TWEAK)和CC趋化因子配体5(CC motif chemokine ligand 5,CCL5)水平在注意缺陷多动障碍(attention deficit hyperactivity disorder,ADHD)患儿诊断、病情严重程度评估中的价值。方法 选取2022年10月~2023年10月在河北省儿童医院就诊的125例ADHD患儿记为ADHD组,另选105例在河北省妇幼保健中心体检的健康儿童为对照组,根据临床总体印象严重程度量表(CGI-S)将患儿分为轻中度组(n=83)和重度组(n=42)。ELISA方法检测血清ACE2,TWEAK,CCL5,促黄体生成素(LH)和催乳素(PRL)水平,联合型瑞文测验(CRT)和Conners父母症状问卷(PSQ)对患儿认知和行为状况进行评分。Spearman相关性分析重度组血清ACE2,TWEAK,CCL5与CGI-S,CRT,PSQ评分的相关性;受试者工作特征(ROC)曲线分析ACE2,TWEAK,CCL5对ADHD及严重程度的诊断价值。结果 ADHD患儿血清ACE2(284.35±92.34 pg/ml),TWEAK(2.56±0.76 pg/ml)水平低于对照组(379.23±106.28 pg/ml,3.52±1.12 pg/ml),CCL5水平(7.36±2.37ng/ml)高于对照组(5.24±1.63 ng/ml),差异具有统计学意义(t=7.244,7.703,7.753,均P<0.05);重度组患儿CRT,血清ACE2,TWEAK水平低于轻中度组(t=5.318,6.686,6.490),而PSQ,CCL5水平较高于轻中度组(t=5.220,6.134),差异具有统计学意义(均P<0.05);Spearman相关性分析结果显示,重度组患儿血清ACE2,TWEAK水平与CGI-S,PSQ评分负相关(r=-0.432,-0.453;-0.421,-0.426,均P<0.001),与CRT评分呈正相关(r=0.427,0.418,均P<0.001);CCL5与CGI-S,PSQ评分呈正相关(r=0.421,0.433,均P<0.001),与CRT评分呈负相关(r=-0.446,P<0.001)。血清ACE2,TWEAK和CCL5诊断ADHD发生的AUC分别为0.814,0.803和0.807,三者联合诊断的AUC为0.945,优于各自单独诊断(Z=5.439,4.258,5.576,均P<0.001);血清ACE2,TWEAK,CCL5诊断重度ADHD的AUC分别为0.853,0.796和0.805,三者联合诊断的AUC为0.930,优于各自单独诊断(Z=2.604,3.851,3.567,均P<0.001)。结论 血清ACE2,TWEAK在ADHD患儿血清中低表达,而CCL5高表达,三者表达水平具有相关性,并且诊断ADHD发生和严重程度具有较高的价值。

红曲霉奶酪的生物活性研究及ACE抑制肽的筛选

研究红曲霉对奶酪成熟过程中生物活性肽,尤其血管紧张素转换酶(angiotensin-converting enzyme,ACE)抑制肽的影响。以不接种红曲霉的奶酪为对照组,研究奶酪成熟过程中的可溶性氮含量、α-葡萄糖苷酶抑制活性和ACE抑制活性,对红曲霉奶酪肽谱进行鉴定,利用生物信息学和分子对接等方法对潜在的活性肽进行筛选,并对筛选肽进行合成和评价。结果表明,相比于对照组,在pH 4.6和三氯乙酸条件下,奶酪成熟结束时的可溶性氮相对含量分别提高57.98%和38.34%,α-葡萄糖苷酶抑制活性和ACE抑制活性分别提高32.21%和73.98%。在红曲霉奶酪提取物中共鉴定到1796种肽,其中51条ACE抑制肽、28条抗氧化肽、7条降血糖肽等。筛选到两种ACE抑制肽YPFPGPI和FPEVFGK,半抑制浓度分别为207.31μmol/L和410.61μmol/L,酶抑制类型均是非竞争性抑制。该研究提供了一种快速筛选ACE抑制肽的方法,证明奶酪中添加红曲霉能够有效提高ACE抑制活性,为挖掘红曲霉奶酪的功能特性潜力提供了参考。

ACE、APN及baPWV预测糖尿病合并高血压发生心脑血管事件的价值

目的 探讨血管紧张素转换酶(ACE)、脂联素(APN)及肱踝脉搏波传导速度(baPWV)预测糖尿病合并高血压发生心脑血管事件的价值。方法 选取2019年1月—2022年2月在我院治疗的糖尿病合并高血压患者138例,随访患者发生心脑血管事件情况,分析比较发生和未发生心脑血管事件患者ACE、APN、baPWV等临床资料差异。结果 发生心血管事件患者BMI、收缩压、甘油三酯(TG)、糖化血红蛋白(HbA1c)、ACE和baPWV明显高于未发生心血管事件患者,而APN明显低于未发生心血管事件(均P<0.05)。Logistic回归分析显示:BMI、收缩压、ACE、APN和baPWV是患者发生心血管事件的影响因素(P<0.05)。发生冠心病、缺血性脑卒中、心源性猝死和脑出血患者性别、年龄、ACE、APN、baPWV等临床资料比较差异无统计学意义(P>0.05)。ACE、APN和baPWV预测心血管事件发生的ROC曲线下面积比较,其中baPWV预测价值明显高于ACE和APN(P<0.05)。结论 ACE、APN及baPWV预测糖尿病合并高血压发生心脑血管事件有较好的应用价值。

槟榔籽提取物对血管紧张素转化酶(ACE)活性的抑制作用研究

以嫩果期槟榔籽为研究对象,采用75%乙醇浸提制得槟榔籽提取物(areca nut extract,ANE),再分别用石油醚、乙酸乙酯和正丁醇依次对总提取物进行萃取,依次得到嫩果期槟榔籽75%乙醇提取物的石油醚部位(PE-ANE)、乙酸乙酯部位(EAC-ANE)、正丁醇部位(BU-ANE)、水部位(W-ANE)的萃取部分。通过体外抑制血管紧张素转化酶(ACE)活性抑制试验测定槟榔提取物各极性部位对高血压的抑制潜力;通过酶动力学实验分析ACE抑制活性最好的极性部位对ACE活性的抑制作用类型;测定不同极性部位蛋白质、总糖及多酚的总含量,并分析其与ACE半抑制浓度(IC50)之间的相关性;最后对4种不同极性部位萃取物中的多酚组分进行初步定量。结果表明:嫩果期槟榔籽提取物各极性部位均具有一定的ACE抑制活性,其中EAC-ANE的ACE抑制活性最好。酶动力学实验表明,EAC-ANE对ACE活性的抑制作用类型为竞争与非竞争的混合型抑制。相关性分析表明,各极性部位ACE的IC50值与多酚、总糖及蛋白质含量均呈显著负相关,且与多酚含量之间具有极强相关性(r=‒0.912)。在4个极性部位中定量了儿茶素、L-表儿茶素、原花青素B2、原儿茶酸、槲皮素等多种多酚组分,且EAC-ANE中的相关多酚组分含量最高。综上所述,槟榔提取物具有一定的降血压潜力,且乙酸乙酯萃取部位最好,多酚含量与各萃取部位的ACE抑制活性具有极强的相关性,可初步推断多酚是槟榔提取物中抑制ACE活性的重要物质。

ACE与ACE2在儿童重症肺炎支原体肺炎中的水平变化及预测价值

目的探讨血管紧张素转化酶(ACE)与血管紧张素转化酶2(ACE2)在儿童重症肺炎支原体肺炎(SMPP)中的水平变化,并评估其在预测SMPP临床发展中的价值。方法选择2020年10月至2023年12月在兰州大学第二医院住院的71例普通肺炎支原体肺炎(MPP)患儿(MPP组)、63例重症肺炎支原体肺炎(SMPP)患儿(SMPP组),并选择同期20名健康体检儿童为健康对照组。测定并比较3组儿童血清中ACE与ACE2质量浓度,同时收集MPP组和SMPP组患儿的实验室检查指标结果进行比较及相关性分析,绘制受试者操作特征(ROC)曲线分析比较不同指标单独及联合预测SMPP的价值。结果3组儿童的血清ACE质量浓度中,SMPP组最高、健康对照组最低;血清ACE2质量浓度中,MPP组最高、健康对照组最低(P均<0.008);与MPP组相比,SMPP组白细胞计数、中性粒细胞百分比、C-反应蛋白(CRP)、淀粉样蛋白A、降钙素原、白介素-6(IL-6)、红细胞沉降率、D-二聚体(D-dimer)水平均升高(P<0.001)且与ACE质量浓度呈正相关(P<0.05)、与ACE2质量浓度呈负相关(P<0.05),SMPP组淋巴细胞百分比(LY%)降低(P<0.001)且与ACE2质量浓度呈正相关(P<0.05)、与ACE质量浓度呈负相关(P<0.05),SMPP组乳酸脱氢酶(LDH)水平较高(P<0.05)且与ACE2质量浓度呈负相关(P<0.05)、与ACE质量浓度无相关性(P>0.05),SMPP组单核细胞百分比(MO%)差异既无统计学意义也无相关性(P均>0.05);ROC曲线分析结果显示ACE、ACE2、CRP、D-dimer、LDH及ACE+ACE2联合检测、CRP+D-dimer+LDH联合检测对SMPP均具有预测价值,其中ACE+ACE2联合检测的预测价值最高,其AUC为0.991(95%CI 0.981~1.000)。结论ACE和ACE2水平很可能与SMPP患儿的病情发生、发展有关,可以作为预测SMPP的良好指标。

Effects of Yinchenhao Decoction on Self-regulation of Renin-angiotensin System by Targeting Angiotensin Converting Enzyme 2 in Bile Duct-ligated Rat Liver

Summary： In order to investigate whether Yinchenhao decoction （YCHD） attenuates hepatic fibro- genesis in the bile duct ligation （BDL） model via recovering and restoring the self-regulation and bal- ance of the renin-angiotensin system （RAS）, 33 specific-pathogen-free （SPF） male Sprague-Dawley rats with common BDL and scission were randomly divided into five groups as follows： G1, the sham group （n=4）; G2, BDL 7-day group （n=5）; G3, BDL＋YCHD 430 mg/mL （n=8）; G4, BDL＋losartan 0.65 mg/mL （ARB group, n=8）; G5, model group （BDL without any treatment, n=8）. YCHD and losartan （10 mL.kgl.day-1） were given by gastric gavage for 16 days following BDL in G3 and G4 groups, respec- tively. The effect of YCHD on liver fibrosis and the detailed molecular mechanisms were assessed by liver function including total bilirubin （TBIL）, direct bilirubin （DBIL）, indirect bilirubin （IDBIL）, alanine aminotransferase （ALT）, and aspartate aminotransferase （AST）. Histological changes were ob-. served by transmission electron microscopy （TEM） and Masson trichrome staining. Western blotting was used to detect the protein expression level of the renin-angiotensin system （RAS） components in- cluding angiotensin converting enzyme （ACE）, angiotensin II type 1 receptor （AT1R）, ACE2, angio- tensin II （Ang II） as well as transforming growth factor 131 （TGF131）. The experimental data were ana- lyzed by principle component analytical method of pattern recognition. The results showed that bio- chemically, serum TBIL, DBIL, IDBIL, ALT and AST levels were markedly increased following BDL as compared with the sham group （P〈0.05）. Serum TBIL, IDBIL and DBIL levels in G3 group were dramatically decreased as compared with G5 and G4 groups （P〈0.05）. Serum AST level in G3 was sig- nificantly lowered than in G5 group （P〈0.05）, but there was no significant difference in ALT among G3, G4 and G5 groups （P〉0.05）. Histologically, livers in G3 group showed less hepatocytes necrosis, less bile duct hyperplasia and less collagen formation than in G4 and G5 groups. The protein expression lev- els of ACE2, ACE, Ang II, AT1R and TGF131 in G2, G3 and G4 groups were significantly higher than in sham group （P〈0.05）, and lower than in G5 group （P〈0.05）. However, the differences among G2, G3 and G4 groups were not significant （P〉0.05）. ACE2 protein expression in G3 group was significantly higher than in G2 group （P〈0.05） and there was no significant difference in comparison with G4 group （P〉0.05）. Moreover, the protein expression of TGF131 in G3 group was significantly lower than in G5 and G4 groups （P〈0.05）. Our findings suggest that the antifibrotic effects of YCHD may be associated with the decreased classical RAS pathway components and TGFI31 downexpression so as to recover and rebuild self-regulation of the RAS by elevating the protein expression of ACE2.

ACE2对猪流行性腹泻病毒体外感染传代猪小肠上皮细胞的影响

为探究血管紧张素转换酶2(angiotensin converting enzyme 2,ACE2)在猪流行性腹泻病毒(porcine epidemic diarrhea virus, PEDV)感染仔猪过程中发挥的作用,本研究通过转录组学分析仔猪肠道ACE2在PEDV感染前后表达的变化情况,然后利用猪小肠上皮细胞(porcine intestinal epithelial cells, IPEC-J2细胞)模型,通过RT-qPCR、Western blot检测PEDV感染后ACE2的mRNA、蛋白表达水平的变化。过表达与抑制表达ACE2后通过RT-qPCR、Western blot、TCID50检测PEDV复制水平。结果显示,PEDV感染IPEC-J2后ACE2的mRNA及蛋白表达水平均显著下调,与转录组学结果一致。过表达ACE2组PEDV感染量显著上升,抑制表达ACE2组PEDV感染量显著下降。本研究在细胞水平上验证了ACE2在PEDV感染过程中的作用,即PEDV感染能够使ACE2表达量下降,在IPEC-J2细胞中过表达ACE2能提高PEDV复制水平,抑制ACE2的表达可降低PEDV复制水平。

Serum levels of angiotensin converting enzyme as a biomarker of liver fibrosis

The renin angiotensin system(RAS) is classically conceived as a circulating hormonal system involved in blood pressure control and hydroelectrolyte balance. The discovery that RAS components are locally expressed in a wide range of organs and tissues,including the liver,pointed to a role for this system in the pathogenesis of several conditions including hepatic fibrosis and cirrhosis. It has been widely reported that the classical RAS axis composed by the angiotensin converting enzyme(ACE)-angiotensin(Ang) Ⅱ-Ang type 1(AT1) receptor mediates pro-inflammatory,pro-thrombotic,and pro-fibrotic processes. On the other hand,the alternative axis comprising ACE2-Ang-(1-7)-Mas receptor seems to play a protective role by frequently opposing Ang Ⅱ action. Chronic hepatitis B(CHB) is one of the leading causes of liver fibrosis,accounting for the death of nearly one million people worldwide. Liver fibrosis is a key factor to determine therapeutic interventions for patients with CHB. However,the establishment of non-invasive and accurate methods to detect reversible stages of liver fibrosis is still a challenge. In an elegant study published in the 36 th issue of the World Journal of Gastroenterology,Noguchi et al showed the predictive value of serum ACE levels in detecting not only advanced stages of liver fibrosis but also initial and intermediate fibrotic stages. The serum levels of ACE might represent an accurate,non-invasive,widely available,and easy method to evaluate fibrosis related to CHB. Moreover,therapies involving the inhibition of the classical RAS axis components might be promising in the control of CHB-related liver fibrosis.

Effect of angiotensin Ⅱ type 1 receptor blocker and angiotensin converting enzyme inhibitor on the intraocular growth factors and their receptors in streptozotocin-induced diabetic rats

AIM： To investigate the effect of angiotensin II type 1 receptor blocker （ARB） and angiotensin converting enzyme inhibitor （ACEI） on intraocular growth factors and their receptors in streptozotocin-induced diabetic rats. METHODS： Forty Sprague-Dawley rats were divided into 4 groups： control, diabetes mellitus （DM）, candesartan- treated DM, and enalapril-treated DM （each group, n---10）. After the induction of DM by streptozotocin, candesartan [ARB, 5 mg/（kg · d）] and enalapril [ACEI, 10 mg/（kg · d）] were administered to rats orally for 4Wko Vascular endothelial growth factor （VEGF） and angiotensin II （Ang II） concentrations in the vitreous were measured using enzyme-linked immunosorbent assays, and VEGF receptor 2 and angiotensin II type 1 receptor （ATIR） levels were assessed at week 4 by Western blotting. RESULTS： Vitreous Ang II levels were significantly higher in the DM group and candesartan-treated DM group than in the control （P=0.04 and 0.005, respectively）. Vitreous ATIR increased significantly in DM compared to the other three groups （P〈0.007）. Candesartan-treated DM rats showed higher vitreal ATIR concentration than the enalapril-treated DM group and control （P〈0.001 and P=0.005, respectively）. No difference in vitreous Ang II and ATIR concentration was found between the enalapril- treated DM group and control. VEGF and its receptor were below the minimum detection limit in all 4 groups. CONCLUSION： Increased Ang II and ATIR in the hyperglycemic state indicate activated the intraocular renin-angiotensin system, which is inhibited more effectively by systemic ACEI than systemic ARB.

A Novel Angiotensin I Converting Enzyme Inhibitory Peptide from the Milk Casein:Virtual Screening and Docking Studies

Angiotensin I converting enzyme （ACE） plays an important physiological role in the regulation of hypertension. In this study, we applied virtual screening to discover a novel angiotensin I converting enzyme inhibitory peptides from milk casein. One potential hit was identified based on docking scores, subsequently confirmed by activity studies in vitro （IC50=20.85 μmol L-1）. The proposed peptide in this study contains a unique sequence, Lys-Val-Leu-Ile-Leu-Ala. Moreover, we performed the docking studies to understand the binding mode between the enzyme and peptide hit.

Angiotensin-converting enzyme and bradykinin gene polymorphisms and cough:A meta-analysis

AIM:To evaluate the association between genetic polymorphisms and angiotensin converting enzyme in-hibitor (ACEI)-related cough,and the race-or ethnicity-related difference in the prevalence of cough attributed to ACEI therapy.METHODS:We conducted a search in PubMed,EM-BASE,Cinahl,and the Cochrane Database without language limitation.A database of 11 studies on ACEI-related cough,with detailed information regarding ACE I/D or bradykinin B 2 receptor polymorphisms,was created.Eligible studies were synthesized using meta-analysis methods,including cumulative meta-analysis.A subgroup analysis was also performed using ethnicity.RESULTS:Six studies were included on ACE I/D poly-morphism (398 Caucasians,723 East Asians),and three studies were included on bradykinin B 2 receptor poly-morphism (300 East Asians).The distribution of ACE genotypes showed significant differences in the entire population (P=0.004) and in East Asians (P=0.005)but not in Caucasians (P=0.23).Allelic frequencies of ACE showed significant differences in East Asians [odds ratio (OR)=1.49 (1.11-2.02)].The meta-analysis with a random effects model showed a significant associa-tion between ACE allele I/D and ACEI-related cough [random effects (RE) OR=1.49 (1.11-2.02),P=0.009] in East Asians,but not in Caucasians [RE OR=0.90 (0.60-1.35)].The allelic frequencies of the bradykinin B 2 receptor gene were significantly different [OR=2.25 (1.42-3.57)].The distributions of the T/C genotypes of the bradykinin B 2 receptor gene were significantly dif-ferent (χ 2=8.366,P=0.015).The meta-analyses re-vealed that there was a significant association between the bradykinin B 2 receptor allele and ACEI-related cough in East Asians [RE OR=2.29 (1.42-3.69),P=0.001].CONCLUSION:ACE I/D and Bradykinin B 2 receptor polymorphisms contributed to the risk of ACEI-related cough in East Asians,but a negative association be-tween ACE I/D polymorphism and ACEI-related cough was observed in Caucasians.

Correlation of angiotensin converting enzyme gene polymorphism with perioperative myocardial protection under extracorporeal circulation

Objective:To observe the expression of angiotensin converting enzyme(ACE),angiotensinⅡ(AngⅡ),cardiac troponin 【cTnⅠ),creatine kinase isozymes(CK-MB) and muscle red protein(Myo) after cardiopulmonary bypass(CPB),and to investigate the association of polymorphisms in angiotensin converting enzyme genes and myocardial injury.Methods:Sixty-three patients suffered from rheumatic mitral stenosis and scheduled for mitral valve replacement with CPB, were randomly divided into three groups according polymorphisms in angiotensin converting enzyme genes:typeⅡ,type ID,type DD(each=21).Blood samples were withdrawn from artery before operation(T1),at the beginning of CPB(T2),30 min after CPB(T3),(T4) at the end of CPB(T5), 2 h after CPB(T6),6 h after CPB(17) to measure the expression of ACE,AngⅡ,cTnⅠ,CK-MB, Myo.Results:The level of ACE during and after CPB were significantly higher than those before CPB(P【0.05).As extension of CPB time,the expression of ACE was increased.The level of cTnⅠ, CK-MB,Myo after CPB were significantly higher than those before CPB(P【0.05).The level of cTnⅠ,CK-MB and Myo were highest at T7,T6 and T5 and T7,respectively.The level of ACE,AngⅡ,cTnⅠin patients with DD genotype was significantly higher than the ID andⅡgenotype(P【 0.05).Besides,the level of ACE,AngⅡin patients with ID genotype was significantly higher than the II(P【 0.05).Conclusions:There is certain correlation between CPB perioperative midterm ACE and cTnⅠ,Myo,CK-MB.ACE DD genotype is a susceptibility gene of the CPB perioperative myocardial injury.

Origin and genomic characteristics of SARS-CoV-2 and its interaction with angiotensin converting enzyme type 2 receptors, focusing on the gastrointestinal tract

The emergence of coronavirus disease-2019 induced by a newly identified bcoronavirus, namely severe acute respiratory syndrome coronavirus 2(SARSCoV-2) has constituted a public health emergency. Even though it was considered a zoonotic disease, the virus has also spread among humans via respiratory secretions. The expression and distribution of angiotensin converting enzyme type 2(ACE2) in various human organs might also show other possible infection routes. High ACE2 ribonucleic acid expression has been identified in the gastrointestinal tract(GI) indicating its importance as a possible infection pathway of SARS-CoV-2. ACE2 induces viral entry into the host and most importantly has been found to be associated with the function of the gut. Its deficiency has been implicated in several pathologies such as colorectal inflammation. The renin-angiotensin system(RAS) is an essential regulatory cascade operating both at a local tissue level and at the systemic or circulatory level. The RAS may be important in the pathogenesis of chronic liver disease and is associated with the up-regulation of ACE2. Thus, the aim of this review is firstly, the analysis of some important general and genome characteristics of SARS-CoV-2 and secondly, and most importantly, to focus on the utility of ACE2 receptors in both SARS-CoV-2 replication and pathogenesis, especially in the GI tract.

Effect of angiotensin converting enzyme gene I/D polymorphism in South Indian children with nephrotic syndrome

Nephrotic syndrome is one of the most common childhood kidney diseases. It is mostly found in the age group of 2 to 8 years. Around 10%-15% of nephrotic syndrome cases are non-responders of steroid treatment(SRNS).Angiotensin converting enzyme(ACE)(I/D) gene association studies are important for detecting kidney disease and herein we assessed the association of ACE(I/D) polymorphism with nephrotic syndrome in South Indian children. We recruited 260 nephrotic syndrome(162 boys and 98 girls) and 218(140 boys and 78 girls) control subjects. ACE I/D polymorphism was analyzed by PCR using genotype allele specific primers. In ACE(I/D), we did not find significant association for the ungrouped data of nephrotic syndrome children and the control subjects. Kidney biopsies were done in 86 nephrotic syndrome cases(minimal change disease, n = 51;focal segmental glomerulosclerosis, n = 27;diffuse mesangial proliferation, n = 8). We segregated them into the minimal change disease/focal segmental glomerulosclerosis groups and observed that the ACE’D’ allele was identified with borderline significance in cases of focal segmental glomerulosclerosis and the ’Ⅰ’ allele was assessed as having very weak association in cases of minimal change disease. ’Ⅱ’ genotype was weakly associated with minimal change disease. Gender specific analysis revealed weak association of’ID’ genotype with female nephrotic syndrome in females. Dominant expression of DD genotype was observed in males with nephrotic syndrome. Our finding indicated that ACE(I/D) has moderate association with focal segmental glomerulosclerosis. However, due to the limited number of biopsy proven focal segmental glomerulosclerosis subjects enrolled, further studies are required to confirm these results.

血清ACE2、miR-421在慢性心力衰竭患者中水平及其临床意义

目的探讨慢性心力衰竭(CHF,心衰)患者血清血管紧张素转换酶2(ACE2)、微小RNA-421(miR-421)表达及与患者心功能的相关性。方法选取2021年3月至2022年10月于北京航天总医院收治的127例CHF患者作为观察组,另外选取150例本院同期无心衰患者作为对照组。记录超声参数左室收缩末期内径(LVESD)、左室舒张末期内径(LVEDD)、左心室射血分数(LVEF)、左室舒张末期容积(LVEDV)、左室收缩末期容积(LVESV);采用酶联免疫吸附法(ELISA)检测血清ACE2表达水平,采用实时荧光定量聚合酶链反应(qRT-PCR)检测血清miR-421表达水平,并进行组间比较;采用Spearman分析CHF患者血清ACE2、miR-421表达水平相关性及两者与超声参数、纽约心脏病协会(NYHA)分级相关性。结果与对照组相比,观察组LVESD、LVEDD、LVEDV、LVESV及血清ACE2、miR-421表达水平均较高(P<0.05),LVEF较低(P<0.05);Spearman分析结果显示,CHF患者血清ACE2与miR-421表达水平呈正相关(P<0.05);CHF患者血清ACE2、miR-421表达水平与LVESD、LVEDD、LVEDV、LVESV、NYHA分级均呈正相关(P<0.05),与LVEF呈负相关(P<0.05)。结论CHF患者血清ACE2、miR-421均为高表达,且两者均与患者心功能状况密切相关,可能用于CHF的临床病情评估。

Role of angiotensin converting enzyme and angiotensinogen gene polymorphisms in angiotensin converting enzyme inhibitor-mediated antiproteinuric action in type 2 diabetic nephropathy patients

AIM To investigate the role of genetic variants of angiotensin converting enzyme(ACE) and angiotensinogen(AGT) genes in the antiproteinuric efficacy of ACE inhibitor therapy in diabetic nephropathy(DN) patients.METHODS In the present study, 270 type 2 diabetes mellitus patients with nephropathy were enrolled and treated with ACE inhibitor(ramipril) and followed at 6 mo for renal function and albumin excretion by estimating serum creatinine, end stage renal disease, and albumin/creatinine ratio(ACR) in urine. Genotyping of ACE I/D and AGT M235 T polymorphisms were performed by using primer specific polymerase chain reaction(PCR) and PCR-RFLP techniques, respectively. RESULTS Forty-eight percent of DN patients(responders) benefited with respect to proteinuria from ACE inhibitor therapy at 6 mo follow-up. A significant reduction in ACR was observed after 6 mo treatment with ACE inhibitor irrespective of whether DN patients were micro-albuminuric(≥ 30 and < 300 mg/g creatinine) or macro-albuminuric(≥ 300 mg/g creatinine) at the time of enrollment. However, macro-albuminuric patients(55%) showed better response to therapy. A reduction in urinary ACR was found independent of genotypes of ACE I/D and AGT M235 T polymorphisms although macro-albuminuric patients having TT genotype showed statistically insignificant increased response(72%). CONCLUSION ACE inhibitor therapy reduced urinary ACR by ≥ 30% in 50% of DN patients and the response is independent of ACE I/D and AGT M235 T polymorphisms.

ACEI和ARB对慢性肾脏病患者预后的影响分析

目的 研讨血管紧张素转化酶抑制剂(ACEI)和血管紧张素Ⅱ受体拮抗剂(ARB)对慢性肾脏病(CKD)患者预后的影响。方法 选取88例慢性肾脏病患者,随机分成对照组、观察组,各44例。对照组采用ACEI治疗,观察组采用ARB治疗。比较两组的治疗效果、肾功能相关指标、心功能指标、生活质量评分、不良反应发生情况。结果 两组的治疗总有效率均较高(P>0.05)。观察组治疗后的尿素氮(9.25±1.05)mmol/L、血肌酐(142.56±32.08)μmol/L均低于对照组的(12.56±5.25)mmol/L、(252.26±55.16)μmol/L,血肌酐清除率(96.41±2.08)ml/min高于对照组的(88.56±8.25)ml/min(P<0.05)。观察组治疗后的左室收缩末期内径(LVESD)(46.25±1.06)mm、左室舒张末期内径(LVEDD)(50.26±0.36)mm小于对照组的(49.26±5.26)、(57.15±2.56)mm,左室射血分数(LVEF)(44.89±1.08)%高于对照组的(41.26±5.62)%(P<0.05)。观察组治疗后的活力状况、生理职能、情感职能、社会功能评分分别为(68.44±1.54)、(64.99±2.10)、(68.48±2.15)、(62.48±1.08)分,均高于对照组的(59.48±6.50)、(58.48±8.10)、(59.48±8.41)、(59.71±0.36)分(P<0.05)。两组的不良反应发生率均较低(P>0.05)。结论 ACEI和ARB治疗慢性肾脏病均有一定疗效,但ARB更能显著改善患者的肾功能指标与心功能指标,更有助于提升生活质量。