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.

Angiotensin-converting enzyme 2 alleviates liver fibrosis through the renin-angiotensin system

The present letter to the editor is related to the study titled‘Angiotensin-converting enzyme 2 improves liver fibrosis in mice by regulating autophagy of hepatic stellate cells’.Angiotensin-converting enzyme 2 can alleviate liver fibrosis by regulating autophagy of hepatic stellate cells and affecting the renin-angiotensin system.

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。

急性胰腺炎继发器官功能衰竭患者凝血功能及外周血TIM-3 TAT ACE2水平变化分析

目的:本研究旨在探究急性胰腺炎继发器官功能衰竭患者凝血功能的变化,并分析外周血中T细胞免疫球蛋白黏蛋白分子3(TIM-3)、凝血酶-抗凝血酶复合物(TAT)以及血管紧张素转换酶2(ACE2)水平的变化。方法:本研究开展时间为2020年8月至2022年8月,研究对象为在我院接受诊疗的118例急性胰腺炎患者,根据亚特兰大分级标准对患者的病情严重程度进行评价,并据此进行分组:轻度组(n=72)和重度组(n=46),对两组患者间的凝血功能指标及外周血TIM-3、TAT、ACE2水平进行比较,并探究患者继发器官功能衰竭与各指标的联系。结果:重度组患者的凝血功能指标(PT、INR、APTT和FIB)和外周血中TIM-3和TAT水平均高于轻度组,ACE2水平低于轻度组(P<0.05);继发组患者的凝血功能指标(PT、INR、APTT和FIB)和外周血中TIM-3和TAT水平均高于未继发组,ACE2水平低于未继发组(P<0.05);经多因素分析可知,PT、INR、APTT、FIB、TIM-3、TAT、ACE2均会影响患者继发器官功能衰竭,其预测患者继发器官功能衰竭的AUC值分别为0.846、0.926、0.819、0.862、0.751、0.847、0.858。结论:在急性胰腺炎患者中,凝血功能异常以及外周血中TIM-3、TAT的升高和ACE2的降低与疾病的严重程度密切相关,对急性胰腺炎继发器官功能衰竭风险有潜在的预测价值。

血清ACE2表达与慢性鼻-鼻窦炎伴鼻息肉患者鼻内镜术后复发的关系

目的 探究血清血管紧张素转换酶2(ACE2)表达与慢性鼻-鼻窦炎伴鼻息肉(CRSwNP)患者鼻内镜术后复发的关系。方法 收集2021年3月至2022年3月在本院进行鼻内镜手术的CRSwNP患者128例,另选取健康体检者100例作为对照。根据CRSwNP患者鼻内镜术后是否复发分为复发组40例和未复发组88例,酶联免疫法检测CRSwNP患者血清ACE2的表达水平。Spearman和Pearson法分析ACE2与病变程度、术后感染、Lund-Mackay评分、Davos评分、嗜酸性粒细胞计数、IL-5、IFN-γ的相关性;Logistic回归分析CRSwNP患者鼻内镜术后复发的影响因素,ROC曲线分析血清ACE2对CRSwNP患者鼻内镜术后是否复发的预测价值。结果 CRSwNP患者血清ACE2表达水平显著低于健康体检者(P<0.05),鼻内镜术后复发组CRSwNP患者血清ACE2表达水平显著低于未复发组(P<0.05)。鼻内镜术后复发组和未复发组患者病变程度、术后感染、Lund-Mackay评分、Davos评分、嗜酸性粒细胞计数、IL-5、IFN-γ比较,差异具有统计学意义(P<0.05);Spearman分析结果表明,ACE2表达与病变程度、术后感染、Lund-Mackay评分和Davos评分呈负相关(P<0.05),Pearson分析结果表明,ACE2表达与IL-5、嗜酸性粒细胞计数呈负相关,与IFN-γ呈正相关(P<0.05);Logistic回归分析结果表明,ACE2、术后感染、IL-5、IFN-γ是CRSwNP患者鼻内镜术后复发的影响因素(P<0.05);ROC曲线分析结果表明,ACE2评估CRSwNP患者鼻内镜术后复发的AUC为0.897。结论 血清ACE2表达与CRSwNP患者鼻内镜术后复发具有密切关系,是患者鼻内镜术后复发的影响因素,对评估CRSwNP患者鼻内镜术后复发具有较好预测价值。

ACE2 rs2074192位点多态性与非乙醇性脂肪性肝病易感性的相关性

目的探讨青岛地区人群血管紧张素转化酶2(ACE2)rs2074192位点多态性与非乙醇性脂肪性肝病(NAFLD)易感性的相关性。方法研究纳入NAFLD病人208例,健康查体者105例。收集受试者的血液标本,提取DNA,应用多聚酶链反应(PCR)检测ACE2基因rs2074192位点的基因型,比较ACE2 rs2074192位点基因型及等位基因频率在NAFLD组及对照组的分布差异。同时收集受试者的临床资料及实验室生化检查结果,比较不同基因型病人临床资料及实验室生化结果的差异。结果NAFLD组和对照组ACE2 rs2074192位点的基因型与等位基因分布差异均无统计学意义(P>0.05)。ACE2 rs2074192位点T等位基因女性携带者体质量指数高于未携带者,T等位基因男性携带者血清葡萄糖水平低于未携带者(t=-2.613、-3.195,P<0.05)。结论青岛地区人群ACE2 rs2074192位点多态性与NAFLD易感性无明显相关性。

装载ACE2的植物来源细胞外囊泡防治PM_(2.5)暴露后细胞损伤

探究装载血管紧张素转化酶2(angiotensin converting enzyme 2,ACE2)的植物来源细胞外囊泡(plant-derived extracellular vesicles,PDEVs)在保护机体抵抗空气污染颗粒物(particulate matter,PM_(2.5))引发的呼吸系统损伤过程中的作用.基于葡萄提取PDEVs并装载ACE2过表达的质粒,通过CCK8实验、二氢乙锭(dihydroethidium,DHE)染色、蛋白免疫印迹、实时荧光定量多聚酶链反应(polymerase chain reaction,PCR)等方法,探究改造后的PDEVs对PM_(2.5)暴露后人支气管上皮细胞(Beas-2B)的保护效果.PM_(2.5)暴露会造成Beas-2B细胞氧化应激、细胞凋亡增加,以及炎症因子增加,而装载ACE2的PDEVs能够有效递送ACE2,从而缓解PM_(2.5)诱导的细胞损伤.因此,PDEVs可作为潜在的递送载体,防治大气PM_(2.5)暴露引发的细胞凋亡及损伤.

血清GSDMD、ACE2在小儿川崎病中的表达水平及临床意义研究

目的 探索血清焦孔素蛋白D(GSDMD)、血管紧张素转化酶2(ACE2)在小儿川崎病(KD)患儿中的表达水平及临床意义。方法 收集2020年1月至2022年1月该院诊治的90例KD患儿为KD组,根据KD患儿是否发生冠状动脉损伤(CAL),将KD组分为CAL组(32例)和非CAL组(58例),选取同期因急性呼吸道感染发热住该院的患儿50例为发热对照组,另选取同期该院儿外科行择期手术的腹股沟斜疝患儿50例为对照组。采用酶联免疫吸附试验检测血清GSDMD、ACE2水平。Pearson相关分析血清GSDMD、ACE2与临床指标的相关性。多因素Logisitic回归分析KD患者发生CAL的影响因素。受试者工作特征(ROC)曲线分析血清GSDMD、ACE2对KD患儿发生CAL的诊断价值。结果 KD组血清GSDMD、ACE2水平高于发热对照组和对照组,差异有统计学意义(均P<0.05)。相比于非CAL组,CAL组KD患儿发热持续时间、丙种球蛋白治疗时间、红细胞沉降率、血小板计数、C反应蛋白、GSDMD、ACE2水平均明显较高,而血钠、白蛋白明显较低,差异有统计学意义(均P<0.05)。Pearson相关分析结果,KD组患儿血清GSDMD、ACE2水平与发热持续时间、丙种球蛋白治疗时间、红细胞沉降率、血小板计数、C反应蛋白呈正相关(均P<0.05),与血钠、白蛋白呈负相关(均P<0.05)。多因素Logistic回归分析结果显示,血清GSDMD、ACE2升高是影响KD患儿发生CAL的独立危险因素。ROC曲线分析结果显示,血清GSDMD、ACE2两项联合检测KD患儿发生CAL的曲线下面积(AUC)及其95%CI为0.918(0.868~0.949),明显大于血清GSDMD、ACE2单项检测的AUC及其95%CI[依次为0.838(0.789~0.887)、0.865(0.811~0.912)],差异有统计学意义(Z=5.116、4.217,均P<0.05)。结论 血清GSDMD、ACE2两项联合检测对于KD患儿发生CAL具有较高的诊断价值。

急性冠脉综合征患者血清ACE2、suPAR水平与氧化应激损伤及不良预后的关系

目的 探讨急性冠脉综合征(Acute coronary syndrome, ACS)患者血清血管紧张素转化酶2(Angiotensin converting enzyme 2,ACE2)、可溶性尿激酶型纤溶酶原激活物受体(Soluble urokinase type plasminogen activator receptor, suPAR)与氧化应激损伤及不良预后的关系。方法 选择2019年9月-2022年9月大兴区人民医院收治的125例ACS患者作为ACS组,并选取与之性别、年龄相匹配的50例冠脉造影结果完全正常者作为对照组,比较两组血清ACE2、suPAR及氧化应激指标[丙二醛(Malondialdehyde, MDA)、过氧化脂质(Lipid peroxide, LPO)、超氧化物歧化酶(Superoxide dismutase, SOD)]水平,并分析血清ACE2、suPAR与氧化应激、不良预后的关系。结果 与对照组比较,ACS组ACE2、suPAR、MDA、LPO升高(P<0.05),SOD下降(P<0.05)。轻度病变、中度病变、重度病变患者ACE2、suPAR及冠脉狭窄Gensini评分显著上升(P<0.05)。ACS患者ACE2、suPAR与MDA、LPO、Gensini评分呈正相关(P<0.05),与SOD呈负相关(P<0.05)。与预后良好患者比较,预后不良患者年龄、发病至就诊时间、Gensini评分、ACE2、suPAR、MDA、LPO升高(P<0.05),LVEF、SOD降低(P<0.05)。年龄、发病至就诊时间、Gensini评分、ACE2、suPAR、MDA、LPO是ACS预后不良的危险因素(P<0.05),LVEF、SOD为其保护因素(P<0.05)。血清ACE2联合suPAR预测ACS预后不良的效能较高,其曲线下面积(Area under curve,AUC)为0.894。结论 ACS患者血清ACE2、suPAR高表达与氧化应激损伤、不良预后显著相关。

血清IL-41及ACE2水平诊断小儿川崎病的临床价值

目的探索川崎病(KD)患儿血清白介素41(IL-41)、血管紧张素转化酶2(ACE2)表达水平及临床诊断价值。方法选取2018年12月—2022年12月合肥市妇幼保健院普儿科诊治KD患儿80例为KD组,根据超声心动图结果,分为冠状动脉损伤(CAL)亚组(n=26)和非CAL亚组(n=54),以同期急性上呼吸道感染伴发热患儿为对照2组(n=40),同期行择期手术的腹股沟斜疝患儿为对照1组(n=40)。采用酶联免疫吸附法检测血清IL-41、ACE2水平;采用Pearson相关分析血清IL-41、ACE2与临床资料的相关性;多因素Logistic回归分析影响KD患儿发生CAL的影响因素;绘制受试者工作特征曲线分析血清IL-41、ACE2预测KD患儿发生CAL的价值。结果血清IL-41、ACE2水平比较,KD组>对照2组>对照1组,差异均有统计学意义(F/P=519.731/<0.001,1115.501/<0.001);KD组患儿血清IL-41、ACE2水平与发热时间、C反应蛋白及降钙素原呈正相关(IL-41:r/P=0.562/<0.001,0.589/<0.001,0.613/<0.001;ACE2:r/P=0.622/<0.001,0.609/<0.001,0.574/<0.001)。CAL亚组发热时间、C反应蛋白、降钙素原、IL-41、ACE2均高于非CAL亚组,差异有统计学意义(t/P=3.459/0.001,11.187/<0.001,11.377/<0.001,12.299/<0.001,25.882/<0.001)。血清IL-41、ACE2、发热时间、C反应蛋白、降钙素原升高是影响KD患儿CAL发生的独立危险因素[OR(95%CI)=1.598(1.271~2.010),1.573(1.241~1.994),1.384(1.142~1.667),1.496(1.171~1.912),1.513(1.159~1.975)]。血清IL-41、ACE2及两项联合预测KD患儿发生CAL的AUC分别0.812、0.815、0.878,两项联合的AUC大于血清IL-41、ACE2单一检测(Z/P=5.116/<0.001、4.217/0.009)。结论KD患儿血清IL-41、ACE2升高,与发热时间、C反应蛋白及降钙素原有关,两者联合对KD患儿CAL发生具有较高的预测价值。

急性胰腺炎患儿血清ACE2、ApoB/A1比值与病情程度及预后的关系

目的研究急性胰腺炎(AP)患儿血清血管紧张素转化酶2(ACE2)、载脂蛋白B/A1(ApoB/A1)比值与病情程度及预后的关系。方法选取2021年4月—2023年10月116例AP患儿,其中轻中症69例、重症47例。比较不同病情程度患儿血清ACE2、ApoB/A1比值及病情程度相关评分[急性胰腺炎严重程度床边指数(BISAP)、Ranson评分、急性生理学与慢性健康状况评分系统Ⅱ(APACHEⅡ)];分析血清ACE2、ApoB/A1比值与病情程度评分的相关性;统计116例患儿预后,比较不同预后患儿血清ACE2、ApoB/A1比值,采用相对危险度分析血清ACE2、ApoB/A1比值对AP患儿预后不良风险的影响;采用受试者工作特征(ROC)曲线评价血清ACE2、ApoB/A1比值对AP患儿预后的预测价值。结果轻中症组血清ACE2水平较重症组高,ApoB/A1比值及BISAP、Ranson、APACHEⅡ评分均低于重症组(P<0.01)。Pearson相关性分析显示,AP患儿血清ACE2水平均与BISAP、APACHEⅡ、Ranson评分呈负相关,ApoB/A1比值均与BISAP、Ranson、APACHEⅡ评分呈正相关(P<0.01)。预后不良患儿血清ApoB/A1比值高于预后良好患儿,ACE2水平低于预后良好患儿(P<0.05)。血清ACE2低水平亚组预后不良风险是高水平亚组的4.667(95%CI:1.416,15.380)倍;ApoB/A1比值高水平亚组预后不良风险是低水平亚组的3.250(95%CI:1.126,9.380)倍。ROC曲线显示,血清ACE2、ApoB/A1比值联合预测AP患儿预后的曲线下面积为0.927,明显高于各指标单独预测。结论血清ACE2、ApoB/A1比值与AP患儿病情程度具有明显相关性,且两项指标联合检测对AP患儿预后有较好预测价值。

老年AECOPD患者血清ACE2、EOS%、SP-D表达水平及预后的评估价值

目的 探讨老年慢性阻塞性肺疾病急性加重期(Acute Exacerbation of Chronic Obstructive Pulmonary Disease,AECOPD)患者血管紧张素转换酶2(Angiotensin-Converting Enzyme 2,ACE2)、嗜酸性粒细胞占白细胞的百分比(Eosinophil Percentage of White Blood Cells,ESO%)、肺表面活性蛋白D(Surfactant Protein D,SP-D)表达水平及预后的评估价值。方法 选取2022年4—12月化州市中医院收治的100例老年AECOPD患者作为研究对象,根据慢性阻塞性肺疾病评估测试(COPD Assessment Test,CAT)量表进行疾病严重程度分级分为轻度组(n=44)、中度组(n=30)、重度组(n=26),对比3组患者ACE2、EOS%、SP-D表达水平,并应用ROC曲线分析血清ACE2、EOS%、SP-D对老年AECOPD患者预后的评估价值。结果重度组AECOPD患者血清ACE2、EOS%、SP-D水平高于轻、中度组,差异有统计学意义(P均<0.05)。血清ACE2、EOS%、SP-D水平以及三者联合预测老年AECOPD患者预后的曲线下面积分别为0.715、0.751、0.854及0.901,敏感度分别为42.9%、71.4%、67.1%及87.1%,特异度分别为90.0%、63.3%、96.7%及90.0%。结论 老年AECOPD患者临床严重性与血清ACE2、EOS%、SP-D水平呈正相关,即疾病严重程度越重,三者水平越高,对于预后评估具有显著的预测性价值,能有效提升预后判断的精确度。

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.

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.

Angiotensin-converting enzyme 2 receptors,chronic liver diseases,common medications,and clinical outcomes in coronavirus disease 2019 patients

The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the virus responsible for coronavirus disease 2019(COVID-19),enters affected cells through the angiotensin-converting enzyme 2(ACE2)receptor,which is highly expressed in type II alveolar cells,enterocytes,and cholangiocytes.SARS-CoV-2 infection causes fever,dry cough,and breathing difficulty,which can progress to respiratory distress due to interstitial pneumonia,and hepatobiliary injury due to COVID-19 is increasingly recognized.The hepatobiliary injury may be evident at presentation of the disease or develop during the disease progression.The development of more severe clinical outcomes in patients with chronic liver diseases(CLD)with or without cirrhosis infected with SARS-CoV-2 has not been elucidated.Moreover,there is limited data related to common medications that affect the disease severity of COVID-19 patients.Additionally,ACE2 receptor expression of hepatobiliary tissue related to the disease severity also have not been clarified.This review summarized the current situation regarding the clinical outcomes of COVID-19 patients with chronic liver diseases who were treated with common medications.Furthermore,the association between ACE2 receptor expression and disease severity in these patients is discussed.

Plasma Levels of Angiotensin-Converting Enzymes 1 and 2 and <i>AGTR</i>2 (T1247G and A5235G) Gene Polymorphisms Are Associated to Breast Cancer Progression

Background: Breast cancer is the most common type of cancer among women. Diagnosed and treated timely, patients may have good prognostics. In Brazil, in 2012, the estimate of new cases was 52,680 and the number of registered deaths in 2012 was 12,852. The Renin-Angiotensin System (RAS) is known for its role in arterial hypertension and in other cardiovascular diseases. Angiotensin-Converting Enzyme 2 (ACE2) is the key to Ang-(1-7) formation, and counterbalances the ACE1/AngII/AGTR1 axis actions. RAS components have complex interactions with different tissues and their actions are not restricted to the cardiovascular system. Recently, the RAS has been associated with different types of cancers and in particular with gynecological cancers. Objectives: Our aim is to investigate possible associations between allelic distribution of two genetic polymorphisms in the AGTR2 receptor with ACEs 1 and 2 plasma levels among women with breast cancer. Patients and Methods: Patients with breast cancer were genotyped for two polymorphisms of the AGTR2 (T1247G and A5235G). Genotyping assays (TaqMan) were performed with genomic DNA extracted from blood cells. ACEs plasma level measurements were conducted in women from the breast-cancer group (N = 53). ACEs were measured in the plasma of these patients using ELISA kits. Results: SNPs genotype distribution is correlated with ACEs plasma levels. ACEs plasma levels are also correlated with clinical variables and ACE2 high levels are associated with better prognostics. Conclusions: Changes in circulating levels of ECA1/AngII ECA2/ Ang-(1-7) determine the magnitude of the inflammatory response that an individual can trigger and the variation in ACE 1 and 2 plasma level measurements in the blood of breast cancer patients suggests an association with the process of mammary carcinogenesis. Thus, the RAS may be associated with the process of mammary carcinogenesis by both genotypic variations of RAS components and by circulating levels of ACEs.

Circulating angiotensin converting enzyme 2 and COVID-19

The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has triggered a widespread outbreak since December 2019.The SARS-CoV-2 infection-related illness has been dubbed the coronavirus disease 2019(COVID-19)by the World Health Organization.Asymptomatic and subclinical infections,a severe hyperinflammatory state,and mortality are all examples of clinical signs.After attaching to the angiotensin converting enzyme 2(ACE2)receptor,the SARSCoV-2 virus can enter cells through membrane fusion and endocytosis.In addition to enabling viruses to cling to target cells,the connection between the spike protein(S-protein)of SARS-CoV-2 and ACE2 may potentially impair the functionality of ACE2.Blood pressure is controlled by ACE2,which catalyzes the hydrolysis of the active vasoconstrictor octapeptide angiotensin(Ang)II to the heptapeptide Ang-(1-7)and free L-Phe.Additionally,Ang I can be broken down by ACE2 into Ang-(1-9)and metabolized into Ang-(1-7).Numerous studies have demonstrated that circulating ACE2(cACE2)and Ang-(1-7)have the ability to restore myocardial damage in a variety of cardiovascular diseases and have antiinflammatory,antioxidant,anti-apoptotic,and anti-cardiomyocyte fibrosis actions.There have been some suggestions for raising ACE2 expression in COVID-19 patients,which might be used as a target for the creation of novel treatment therapies.With regard to this,SARS-CoV-2 is neutralized by soluble recombinant human ACE2(hrsACE2),which binds the viral S-protein and reduces damage to a variety of organs,including the heart,kidneys,and lungs,by lowering Ang II concentrations and enhancing conversion to Ang-(1-7).This review aims to investigate how the presence of SARS-CoV-2 and cACE2 are related.Additionally,there will be discussion of a number of potential therapeutic approaches to tip the ACE/ACE-2 balance in favor of the ACE-2/Ang-(1-7)axis.

AT1a Receptor Has Interacted with Angiotensin-converting Enzymes 2 mRNA Expression in Mouse Brainstem

Objectives To examine in vivo interactions between angiotensin Ⅱ （Ang Ⅱ ） AT1 a receptor （AT1 aR）, angiotensin-converting enzymes （ACE） and ACE2 using small hairpin RNA （shRNA） gene-silencing methods in mice brainstem nucleus tractus solitarius （NTS）. Methods C57BL mice （n = 8 ） were used as animal model. Method of micro-injection in the nucleus of NTS was adopted. After ten days, mice were killed and their brain tissue were fixed and sectioned. The expression levels of AT1 aR, ACE and ACE2 mRNA at both sides of NTS were examined by in situ hybridization. Based on compared t-test, the changing for mRNA expression was examined. Results After the expression of ATlaR mRNA was significantly inhibited （61.6% ± 6.8% ） by ATlaR-shRNA, it was associated with decreases in ACE2 mRNA expression from （ 1.05 ± 0. 12） μCi/mg to （0. 74 ± 0.09 ） μCi/mg （ 29.0% ± 14. 5% , P 〈 0. 01 ） on the same side of the brainstem. ACE mRNA expression was consistent at both sides （ 0. 50 μCi/mg ± 0. 09μCi/mg and 0. 53 μCi/mg ± 0. 08 μCi/mg）, with insignificant difference （ P 〉 0. 05 ）. Conclusions The gene silencing result showed that there were interactions between brainstem AT1 aR and ACE2. ACE mRNA expression was not altered by RNA interference treatment at AT1 aR.

ACE2在结肠癌中表达的临床意义及结肠癌细胞对以ACE2为受体的三种人冠状病毒的易感性分析

目的分析血管紧张素转化酶2(angiotensin-converting enzyme 2,ACE2)在结肠癌中的表达及与结肠癌患者预后的关系,探讨结肠癌细胞对以ACE2为受体的三种人冠状病毒的易感性。方法利用实时荧光定量聚合酶链式反应、免疫组织化学和蛋白质免疫印迹,探究结肠癌组织和细胞中ACE2的表达,并结合数据库分析ACE2的表达与结肠癌患者预后的关系。借助人冠状病毒假病毒分析结肠癌细胞对人冠状病毒假病毒的易感性。结果结肠癌组织和细胞中ACE2的表达水平明显升高。且ACE2的表达水平与结肠癌患者预后无关。与结肠上皮细胞CCC-HIE-2相比,结肠癌细胞Caco2对重症急性呼吸综合征冠状病毒假病毒的易感性显著升高。除HCT-15细胞外,所有结肠癌细胞对新型冠状病毒假病毒的易感性明显升高。所有结肠癌细胞对人冠状病毒NL63假病毒的易感性明显升高。结论ACE2在结肠癌组织和结肠癌细胞中表达增加且其表达与结肠癌患者预后无关,大部分结肠癌细胞对三种人冠状病毒的易感性增加。

溃疡性结肠炎患者血清Rac1、ACE2水平与肠道功能损害的相关性

目的探讨溃疡性结肠炎(ulcerative colitis,UC)患者血清Ras相关的C3肉毒素底物1(Rac1)、血管紧张素转化酶2(ACE2)水平与肠道功能损害的相关性。方法选取2020年3月至2022年3月驻马店中心医院就诊的UC患者60例为病例组,依据Mayo评分将病例组分为活动期组(36例)、缓解期组(24例),同时以同期健康体检者40例为对照组。分别静脉抽取所有研究对象空腹血液,ELISA法检测血清ACE2水平;q RT-PCR检测血清中Rac1 m RNA水平;同时检测肠道屏障指标(血清二胺氧化酶、细菌内毒素、D-乳酸)水平;采用Pearson法分析UC患者血清中ACE2、Rac1 m RNA水平的相关性以及两者分别与血清二胺氧化酶、细菌内毒素、D-乳酸的相关性。结果与对照组相比,病例组血清中ACE2、Rac1 m RNA水平显著下降,二胺氧化酶、细菌内毒素、D-乳酸水平显著增加(P<0.05);与缓解期组相比,活动期组ACE2、Rac1 m RNA水平显著下降(P<0.05);Pearson法结果显示,UC患者血清中ACE2与Rac1水平呈明显正相关(r=0.390,P<0.05),且分别与二胺氧化酶、细菌内毒素、D-乳酸呈负相关(P<0.05)。结论UC患者血清中ACE2与Rac1水平呈正相关,且分别与肠道屏障指标呈负相关,检测两者水平对于评定肠道功能损害可能具有一定临床价值。