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groups according polymorphisms in angiotensin converting enzyme genes:typeⅡ,type ID,type DD(each=21).Blood samples were withdrawn from artery before operation(T1),at the beginning of CPB(T2),30 min after CPB(T3),(T4) at the end of CPB(T5), 2 h after CPB(T6),6 h after CPB(17) to measure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.

Effects of angiotensin converting enzyme inhibitors on cognitive function, apoptosis and oxidative stress in brain tissue of rats with cerebral infarction

Objective:To study the effects of angiotensin converting enzyme inhibitor(ACEI)on cognitive function,apoptosis and oxidative stress in brain tissue of rats with cerebral infarction.Methods:Adult male SD rats were randomly divided into control group,cerebral infarction group and ACEI group.The latter two groups were used to establish cerebral infarction model by thread embolism.The ACEI group was given oral administration of fosinopril 10mg/kg,and the other two groups were given oral administration of saline.The differences of Morris water maze cognitive function,apoptotic genes and oxidative stress indexes were compared among the three groups.Results:The escape latency of rats in cerebral infarction group was significantly longer than that in control group,the number of times of platform crossing was significantly less than that in control group,the duration of platform stay was significantly shorter than that in control group,the mRNA expression levels of Bcl-2 associated X protein(Bax),factor associated suicide(Fas),Fas ligand(FasL)and Caspase-3,the protein expression levels of phosphorylated Janus kinase(p-JAK2)and phosphorylated signal transducer and activator of transcription(p-STAT3)as well as the contents of reactive oxygen species(ROS)and malonaldehyde(MDA)in brain tissue were significantly higher than those in control group,and the mRNA expression level of B-cell lymphoma-2(Bcl-2)as well as the contents of catalase(CAT)and superoxide dismutase(SOD)in brain tissue was significantly lower than those in control group.The escape latency of rats in ACEI group was significantly shorter than that in cerebral infarction group,the number of times of platform crossing was significantly more than that in cerebral infarction group,the duration of platform stay was significantly longer than that in cerebral infarction group,the mRNA expression levels of Bax,Fas,FasL and Caspase-3,the protein expression levels of p-JAK2 and p-STAT3 as well as the contents of ROS and MDA in brain tissue were significantly lower than those in cerebral infarction group,and the mRNA expression level of Bcl-2 as well as the contents of CAT and SOD in brain tissue was significantly higher than those in cerebral infarction group.Conclusions:ACEI can improve the cognitive function of rats with cerebral infarction and inhibit the apoptosis and oxidative stress in ischemic brain tissue.

Interaction and Relationship Between Angiotensin ConvertingEnzyme Gene and Environmental Factors Predisposing toEssential Hypertension in MongolianPopulation of China

Objective To investigate the association of specific functional gene ACE (I/D) variants of the renin-angiotensin system with essential hypertension (EH) and interaction between ACE (I/D) gene and risk factors for EH in a genetically homogenous Mongolia rural population of China. Methods Individuals (n=1099) were recruited from general population of Kezuohouqi Banner in Inner Mongolian Autonomous Region. Results The association was found between ACE genotype DD plus ID and EH, with an interaction between ACE genotype DD plus ID and cigarette smoking in an additive model. Cigarette smoking index and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 7.10 to 1.16. Interaction between ACE genotype DD plus ID and alcohol drinking on EH appeared an additive model. Alcohol drinking index and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 1.66 to 1.09. BMI and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 6.15 to 2.49. Interactions between ACE genotype and WHR on EH showed a multiplicative model. In a short, there was an interaction between ACE gene and cigarette smoking, alcohol drinking and BMI on EH, especially in a low dose-exposure effect Conclusion It is important for individuals who carry ACE D allele gene to prevent EH, and furthermore, to prevent and control coronary heart disease, in a view of population-based prevention.

POLYMORPHISM OF ANGIOTENSIN CONVERTING ENZYME GENE AND GENETIC SUSCEPTIBILITY TO ASTHMA WITH FAMILIAL AGGREGATION

Angiotensin converting enzyme (ACE) plays a key role in the metabolism of angiotensin Ⅱ (AT Ⅱ) and inactivation of bradykinins and tachykinins, which are potent bronchialconstrictors and mediators of inflammation asthma, and ACE is heavily expressed in the lungs. An insertion deletion (D/I) polymorphism of ACE gene has been shown to be associated with levels of ACE. We investigate whether the polymorphism of ACE gene is associated with asthma and bronchial responsiveness. Methods. A case control study was carried out in 50 asthmatics, 7 families with at least 2 asthmatic individuals, and 50 healthy subjects. The insertion/deletion (I/D) polymorphism of ACE gene was amplified by polymerase chain reaction (PCR). Methacholine brocho provocation and pulmonary function tests were performed in all asthmatics. Results. There was an higher gene frequency of DD genotype of ACE gene in asthmatic subjects and families individuals compared with healthy subjects (46%, 53% vs 16%, P<0 05; odd ratio 4 98). Anhigher prevalence of DD genotype of ACE was in patients with bronchial hyperresposiveness (BHR) (67%vs 33%, P<0 05; odd ratio 3 8). Accordingly, the mean values of FEV 1% and FEV 1/FVC were higher in asthmatics carrying non DD alleles than patients with DD genotype (73 78% vs 56 56%, P<0 05; 79 19% vs 69 29%, P<0 05, respectively). Conclusion. These results suggested that DD allele of ACE genotype was significantly involved in genetic susceptibility to asthma. DD genotype of ACE might be a risk factor for the degree of airway obstruction, it could also be implicated in pathogenesis of bronchial hyperresponsiveness.

Association of Angiotensin Converting Enzyme Gene I/D Polymorphism With Type 2 Diabetes Mellitus

Objective To investigate the association of angiotensin converting enzyme （ACE） gene insertion/deletion （I/D） polymorphism with type 2 diabetes mellitus （T2DM）. Methods Two hundred and nine patients with T2DM diagnosed based on the criteria for diabetes mellitus in 1999 by WHO and 221 controls were recruited from general population of Dongcheng District in Beijing. All subjects were genotyped for the I/D polymorphism of ACE gene by PCR-fragment length polymorphism （FLP） assay. Blood pressure, levels of plasma glucose, lipids and serum insulin were determined. Body mass index （BMI）, waist-trip ratio （WHR） and homeostasis model assessment-insulin resistance index （HOMA-IR） were calculated. Results The genotype frequencies for ACE genes DD, ID, and II were 19.1%, 42.1%, and 38.8% in patients, respectively, and 9.6%, 49.4%, and 41.0% in controls, respectively. The ACE DD genotype frequency was significantly higher in patients than in controls （χ^2=7.61, P=0.022）. Multivariate logistic regression analysis showed that the ACE DD genotype was a risk factor for T2DM, with the OR of 2.35 （95% CI 1.17-4.71） adjusted for age, sex, BMI, WHR, blood pressure, and serum cholesterol levels. Conclusion The ACE DD genotype is associated with the increased susceptibility to type 2 diabetes mellitus.

BENEFICIAL EFFECTS OF CAPTOPRIL ON PROGNOSIS IN ELDERLY PATIENTS WITH ACUTE MYOCARDIAL INFARCTION

Objective. This study sought to investigate the effects of early and long-term intervention with an- giotensin-converting enzyme(ACE) inhibitor captopril on the elderly patients with acute myocardial in farc- tion(AMI), and observe its in-hospital and post-hospital outcomes during serial follow-up of 54 months. Methods. 631 elderly patients(60～75 years old) with AMI and without cardiogenic shock were hospi- talized within 72 hours of symptoms and were randomly allocated to captopril (n = 361;treatment group) and conventional treatment (n = 270; control group). The survival and cardiac events (congestive heart fail- ure, reinfarction, severe arrhythmias and cardiac death)of each group were determined during hospitaliza-tion and follow-up. Results. During hospitalization, the survival was higher in treatment group than in control group(p< 0. 0001 ). On the other hand, in treatment group lower mortality was true for patients with anterior my- ocardial infarction(p < 0. 001 ) or with anterior+inferior myocardial infarction (P= 0. 026 ), but not statis- tically significant in ones with inferior myocardial infarction (P= 0. 061 ). During follow-up, the occurrence of cardiac death, heart failure, reinfarction and severe arrhythmias were lower in treatment group (P = 0. 0001, P = 0. 05, P = 0. 0004 and P = 0. 027). So higher survival (P = 0. 005 ) and lower total cardiac events(p= 0. 0008) could be seen in treatment group over this period. Conclusions. Early and long-term treatment with captopril in the elderly patients with AMI has bene-ficial outcomes in both in-hospital and follow-up periods.

COMPARATIVE EFFECTS OF LOSARTAN AND CAPTOPRIL ON VENTRICULAR REMODELING AND FUNCTION AFTER MYOCARDIAL INFARCTION IN THE RAT

Objective. To determine the effects of losartan and captopril treatment on ventricular remodeling and function after myocardial infarction in rats. Methods. Thirty-two rats with MI induced by coronary ligation after seven days were divided into four groups randomly and treated with captopril(2 g. liter-1, group A), losartan(10 mg. kg-1. d-1, group B), losartan(30 mg. kg-1. d-1,group C) and placebo (no drug, group D) for six weeks, respectively. Shamoperated rats(group E)served as controls. Echocardiography was performed at 1 and 7 weeks after MI, re- spectively. Results. Compared with the results before treatment,both LV end-diastolic internal diameter and volume decreased significantly and the thickened Posterior wall was reversed in group A, B and C; the peak early filling velocity decreased whereas the peak velocity was increased in these three groups. There are no significant difference among the three treated groups. However,LV end-diastolic internal diameter and the E/A were still increased,whereas the thickness of anterior wall and the peak velocity of LV outflow were decreased in group A,B,and C after treatment comparing with group E. Conclusion. Both angiotensin converting enzyme inhibitor and angiotensin II receptor antagonist can prevent the ventricular remodeling and improve the ventricular function.

Left ventricular hypertrophy in relation to systolic blood pressure and the angiotensin converting enzyme I/D polymorphism in Chinese

在那里的目的几乎不在中国是流行和左室的肥大(LVH ) 的环境或基因的决定因素上的很少基于人口的数据。这份报纸的目的是在与变换酶(王牌) 的收缩血压和血管收缩素的关系学习 LVH 用汉语的插入 / 删除(I/D ) 多型性。我们记录了 12 铅 ECG 的方法(CardioSoft， v4.2 ) 在在 Jingning 县的 1365 个居民，浙江省，中国。LVH 根据性特定的 Sokolow 苏格兰纹章院长官和 Comell 产品 ECG 标准被定义。不管Sokolow苏格兰纹章院长官或 Comell 产品 ECG 标准是否被使用结果， LVH 的流行(20.7%和4.8%，分别地)显著地( P < 0.0001 )与男性增加了(机会比率[或] 2.33 和 7.15 )并且收缩血压(每 10 公里 Hg 增加，或 1.46 和 1.33 )。如果 Sokolow 苏格兰纹章院长官标准被使用， LVH 的流行被白酒吸入也影响(或 1.44， P=0.03 ) 并且身体团索引(或 0.83， P=0.0005 ) 。在 Sokolow 苏格兰纹章院长官电压振幅和 ACE I/D 多型性之间的协会依赖于 antihypertensive 治疗(P=0.01 ) 。在 antihypertensive 药上的 1262 个未经治疗的题目，然而并非 103 个病人，王牌 DD 与题目相比有显著地更高的 Sokolow 苏格兰纹章院长官电压振幅(29.8 敢漠 ? 桴 ? 牧癡? 牴楡吗？

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.

CLINICAL OUTCOMES OF FIVE-YEAR FOLLOW-UP OF EARLY AND LONG-TERM TREATMENT WITH CAPTOPRIL ON THE PATIENTS WITH ACUTE MYOCARDIAL INFARCTION

Objective To investigate clinical outcomes of early and long-term treatment with captopril on patients with acute myocardial infarction (AMI) during a five-year follow-up. Methods In a randomi- zed trial, 822 patients (623 males, 199 females) with a first AMI with less 72h of symptoms were treated with captopril (treatment group, n=478, dosage from a first 6.25mg to 25mg t.i.d ) and conventional treatment (control group, n=344). Multivariable Cox’ regression were used to analyze relative risk of independent variables. Cumulative survival of both groups were calculated with Kaplan-Meier analysis and analyzed by using log-rank comparison. Results During the five-year follow-up, the age, Killip class (≥Ⅱ), anterior infarction, diabetes mellitus, and peak CPK increased relative risk of death after AML, but the effects of captopril, beta-blocker, antiplatelet drug, and thrombolytic therapy on the relative risk of death were contrary. The cumulative survival in different time during follow-up was higher in patients with captopril than controls (P< 0.001). Conclusion Early and long-term treatment with captopril was related to a beneficial outcome during the five-year follow-up after AMI.

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。

口服益生菌对慢性心力衰竭患者肠道微生态的影响分析

目的 探讨益生菌在慢性心力衰竭(CHF)患者中的应用效果及对肠道微生态的影响。方法 选取112例CHF患者作为研究对象,随机分为研究组和对照组,每组56例。对照组采用血管紧张素转化酶抑制剂(ACEI)联合血管紧张素Ⅱ受体阻滞剂(ARB)治疗,研究组在对照组的基础上联用双歧杆菌活菌胶囊治疗。检测2组患者心肌纤维化指标[Ⅰ型胶原前体C前肽(PⅠCP)、Ⅲ型胶原前体N前肽(PⅢNP)、PⅠCP/PⅢNP、Ⅰ型胶原羧基端肽(ⅠCTP)]水平、心功能指标[左心室射血分数(LVEF)、左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)、左心室收缩末期容积(LVESV)]、肠道菌群丰度、血浆氧化三甲胺(TMAO)水平和血清肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)水平。观察2组患者的治疗效果、用药安全性及出院后3个月内再入院率、病死率。结果 研究组总有效率为71.43%,高于对照组的51.79%,差异有统计学意义(P<0.05);治疗后,研究组LVEF高于对照组,LVEDD、LVESD、LVESV小于对照组,差异有统计学意义(P<0.05);治疗后,研究组PⅠCP/PⅢNP高于对照组,ⅠCTP低于对照组,差异有统计学意义(P<0.05);治疗后,研究组变形菌门、放线菌门、厚壁菌门、梭杆菌门丰度均低于对照组,拟杆菌门丰度高于对照组,差异有统计学意义(P<0.05);治疗后,研究组TMAO、TNF-α、IL-1β水平低于对照组,差异有统计学意义(P<0.05);用药后,2组患者均未发生严重不良反应;出院3个月内,研究组再入院率为12.50%,低于对照组的30.36%,差异有统计学意义(P<0.05),研究组、对照组患者病死率分别为1.79%、7.14%,差异无统计学意义(P>0.05)。结论 益生菌联合ACEI和ARB治疗方案能有效减轻CHF患者心肌纤维化,并改善肠道微生态及预后。

敲减miR-296-5p通过激活ACE2信号通路减轻脑梗死后神经功能损伤

目的:探究微小RNA-296-5p(miR-296-5p)对脑梗死(CI)后神经功能损伤的影响及其与血管紧张素转换酶2(ACE2)信号通路介导的内皮祖细胞(EPC)活力的调节关系。方法:选取本院70例确诊为CI且伴有神经功能损伤的患者血清标本(CI组)和70例健康志愿者的血清标本(健康组),RT-qPCR法检测两组血清miR-296-5p、ACE2和Mas mRNA的表达。构建大鼠CI模型,将SD大鼠随机分为健康对照组、模型对照组、sh-miR-296-5p组和ACE2过表达组(OE-ACE2组)。对各组大鼠进行神经功能损伤严重程度评分(NSS)。TTC染色法观察各组大鼠CI情况。RT-qPCR法检测大鼠血清miR-296-5p、ACE2和Mas的mRNA表达。分离并常规培养EPC,将EPC随机分为对照组(control组)和sh-miR-296-5p组、OE-ACE2组、OE-miR-296-5p+OE-ACE2组和sh-miR-296-5p+sh-ACE2组。CCK-8法测定EPC活力情况。流式细胞术检测EPC凋亡情况。RT-qPCR法检测EPC中miR-296-5p、ACE2和Mas mRNA的表达。双萤光素酶报告基因实验验证miR-296-5p和ACE2的关系。结果:(1)临床试验:与健康组相比,CI患者血清miR-296-5p水平显著上升(P<0.05),ACE2和Mas的mRNA表达水平显著降低(P<0.05)。(2)动物实验:与健康对照组相比,模型对照组大鼠的NSS评分、CI面积、血清miR-296-5p水平和Mas mRNA表达水平显著上升(P<0.05),ACE2 mRNA表达水平显著降低(P<0.05)。与模型对照组相比,sh-miR-296-5p组和OE-ACE2组大鼠NSS评分、CI面积、血清miR-296-5p水平和Mas mRNA表达水平显著降低(P<0.05),ACE2 mRNA表达水平显著升高(P<0.05)。(3)细胞实验:与control组相比,sh-miR-296-5p组和OE-ACE2组EPC细胞的A450和miR-296-5p水平显著降低(P<0.05),细胞凋亡率及ACE2和Mas mRNA表达水平显著升高(P<0.05)。与sh-miR-296-5p组相比,shmiR-296-5p+sh-ACE2组细胞的A450和miR-296-5p水平显著升高(P<0.05),细胞凋亡率及ACE2和Mas mRNA表达水平显著降低(P<0.05)。与OE-ACE2组相比,OE-miR-296-5p+OE-ACE2组细胞的A450、miR-296-5p水平显著升高(P<0.05),细胞凋亡率及ACE2和Mas mRNA表达水平显著降低(P<0.05)。结论:敲减miR-296-5p可能通过介导ACE2信号通路,抑制EPC活力,减轻CI后神经功能损伤。

ACA、ACE联合血清锌离子浓度对老年急性心肌梗死合并心力衰竭的诊断及预后预测

目的探讨抗心磷脂抗体(ACA)、血管紧张素转换酶(ACE)联合血清锌离子浓度对老年急性心肌梗死合并心力衰竭的诊断及预后预测。方法选取2020年3月—2023年3月内蒙古自治区人民医院收治的84例急性心肌梗死合并心力衰竭患者作为心力衰竭组,选取同期治疗的80例单纯急性心肌梗死未并发心力衰竭患者作为非心力衰竭组。比较两组患者ACA、ACE及血清锌离子浓度,建立受试者特征(ROC)工作曲线分析ACA、ACE联合血清锌离子对老年急性心肌梗死合并心力衰竭的诊断价值。随后将84例急性心肌梗死并发心力衰竭患者中院内死亡者分为死亡组(20例),将其余患者分为存活组(64例),比较两组患者临床一般情况,并分析ACA、ACE及血清锌离子浓度对急性心肌梗死合并心力衰竭预后的预测价值。结果心力衰竭组ACA、ACE水平明显高于非心力衰竭组,锌离子浓度明显低于非心力衰竭组,差异有统计学意义(P<0.05);ACA、ACE联合血清锌离子三者联合对老年急性心肌梗死合并心力衰竭的诊断效能优于单一检测。存活组与死亡组患者性别、年龄、身体素质指数(BMI)、合并糖尿病、高血压、高脂血症、左心室射血分数、支架数、支架长度比较,差异无统计学意义(P>0.05);存活组与死亡组患者Killip分级、合并陈旧性心肌梗死、ACA、ACE及血清锌离子浓度比较,差异有统计学意义(P<0.05);Logistic回归分析结果表明,Killip分级、ACA、ACE及血清锌离子为急性心肌梗死合并心力衰竭预后的独立预测指标。结论ACA、ACE联合血清锌离子浓度对急性心肌梗死合并心力衰竭诊断价值较高,且临床可考虑通过ACA、ACE及血清锌离子浓度来预测急性心肌梗死合并心力衰竭患者的预后情况。

CHRONIC EFFECTS OF EARLY ANGIOTENSIN-CONVERTING ENZYME INHIBITOR (QUINAPRIL) OR ANGIOTENSIN II RECEPTOR BLOCKADE (LOSARTAN) ON HEMODYNAMICS AND REMODELING IN RATS AFTER EXPERIMENTAL MYOCARDIAL INFARCTION

The long-term effects of an angiotensin-converting enzyme (ACE) inhibitor on hemodynamics and remodeling

What is the optimal initiation timing of angiotensin converting enzyme inhibitor treatment for maximum benefits in acute myocardial infarction patients？

Randomized clinical trials led to the clinical recommendation that angiotensin-converting enzyme inhibitors （ACEI） should be used as standard therapy in most patients experiencing an acute myocardial infarction （AMI）. However, the optimal initiation timing of treatment, as well as the exact mechanisms, have not been completely resolved, especially with the development of reperfusion strategy after AMI. Earlier initiation of ACEI might be associated with more prompt recovery of left ventricular ejection fraction due to more rapid attenuation of negative remodeling.

Effect of losartan and captopril on expression of cardiac angiotensin Ⅱ AT1 receptor mRNA in rats following myocardial infarction

目的：探讨氯沙坦（Ｌｏｓ）和卡托普利（Ｃａｐ）对大鼠心肌梗死后血管紧张素Ⅱ（Ａｎｇ）ＡＴ１受体ｍＲＮＡ表达的影响．方法：２４只梗死大鼠随机分为四组并分别用Ｃａｐ（２ｇ·Ｌ－１加水中饮用）、Ｌｏｓ（１０ｍｇ·ｋｇ－１·ｄ－１和３０ｍｇ·ｋｇ－１·ｄ－１，灌胃）及安慰剂治疗６周，假扎鼠作对照，用地高辛标记的ｃＤＮＡ探针，进行点杂交反应，检测ＡｎｇＡＴ１受体ｍＲＮＡ表达．结果：三个药物治疗组的ＡｎｇＡＴ１受体ｍＲＮＡ表达水平分别与安慰剂组比较，均显著降低（Ｐ＜００１）．三个治疗组之间的ＡｎｇＡＴ１受体ｍＲＮＡ表达水平及分别与假扎组比较，均无显著差异（Ｐ＞００５）．结论：Ｃａｐ和Ｌｏｓ均可逆转大鼠心肌梗死后ＡｎｇＡＴ１受体ｍＲＮＡ表达水平的增高．

沙库巴曲缬沙坦治疗急性心肌梗死合并射血分数保留型心力衰竭的疗效及预后分析

目的:本研究分析比较沙库巴曲缬沙坦(sacubitril valsartan,ARNI)对比ACEI/ARB治疗急性心肌梗死合并射血分数保留型心力衰竭(post myocardial infarction heart failure with preserved ejection fraction,P-MI-HFpEF)患者预后的差异。方法:本研究为回顾性研究,连续纳入从2020年8月至2021年8月,于濉溪县医院住院的P-MI-HFpEF患者共231例。根据出院服用药物情况分为ARNI组和ACEI/ARB组。对两组的一般资料、实验室检验检查、合并症及出院带药情况进行比较。利用Kaplan-Meier分析与Cox回归模型分析两组与主要不良事件(major adverse events,MAE)的关系。结果:在P-MI-HFpEF患者中,与ACEI/ARB相比,ARNI组患者的年龄更小、血钾水平偏高、有高血压病史患者人数偏少。ARNI使用与更多的LVEF提高,LVEDD缩小、NT-proBNP减低和MAE(包括因心力衰竭住院和死亡)的发生率减少相关。即使调整了年龄、吸烟、性别、BMI、心肌梗死类型、收缩压、舒张压、心率、血肌酐、cTnI、NT-proBNP、心房颤动病史、高血压病史、卒中史、糖尿病史、β受体阻滞剂、PCI治疗后,ARNI使用者发生MAE风险较ACEI/ARB仍显著下降(HR=0.52,95%CI:0.28~0.97,P=0.041)。结论:在P-MI-HpEF患者中,ARNI相较于ACEI/ARB使用者,可以更好的改善患者的心功能,减少近期主要不良事件的发生。

早期使用β受体阻滞剂和ACEI对接受冠状动脉介入治疗的STEMI患者近中期预后的影响

目的探讨早期使用β受体阻滞剂和ACEI对接受冠状动脉介入治疗的ST段抬高型心肌梗死(ST-segment Elevation Myocardial Infarction,STEMI)患者近中期预后的影响。方法选取2018年5月~2021年11月在本院就诊的STEMI82例,采用随机数字表法分组,即对照组、观察组,均41例。两组均予以β受体阻滞剂和血管紧张素转换酶抑制剂(Angiotension Con-verting Enzyme Inhibitor,ACEI)治疗,仅干预时间不同,其中对照组在介入治疗后至出院前时期应用。观察组在确诊后和介入前进行早期治疗。统计两组患者纽约心脏病协会(New York Heart Association,NYHA)分级、心功能、恶性心律失常发生率、再梗死率及死亡率。结果观察组NYHA分级显著优于对照组,观察组Ⅰ级占比75.61%明显高于对照组,Ⅱ级、Ⅲ级及Ⅳ级也均低于对照组,差异具有统计学意义(P<0.05)。干预前,两组LVESV、LVEDD、LVEF比较,差异无统计学意义(P>0.05),干预后,两组LVESV、LVEDD均下降,LVEF上升,组间比较,观察组LVESV、LVEDD低于对照组,LVEF高于对照组,差异具有统计学意义(P<0.05)。观察组恶性心律失常发生率2.44%、再梗死率0及死亡率4.88%均低于对照组,差异具有统计学意义(P<0.05)。结论STEMI患者早期予以β受体阻滞剂和ACEI治疗,可减少恶心心律失常、再梗死及死亡发生率,改善心功能,值得推广。

Screening for urinary markers predicting hematopoietic stem cell injury induced by busulfan using genetically diverse mice

Background:Busulfan(BU)is an alkylating agent used as a conditioning agent prior to hematopoietic stem cell(HSC)transplantation as it is known to be cytotoxic to host hematopoietic stem and progenitor cells.The susceptibility of HSCs to BU injury plays an important role in the myeloablative efficacy of BU.Different susceptibilities were demonstrated in genetically diverse(GD)mice in our preliminary research.Methods:Three strains of GD mice with different susceptibilities to BU-i nduced HSC injury were used for screening biological markers of HSC injury susceptibility in urine.The urine proteins were analyzed using liquid chromatography coupled with tandem mass spectrometry to screen for differentially expressed proteins.Screening for possible biomarkers based on differences in protein expression abundance was validated using enzyme-l inked immunoassay(ELISA).Results:Functional analysis showed that the differential proteins were all involved in a series of biological pathways related to cellular senescence,apoptosis,and angiogenesis;whereas the differential proteins of the high-susceptible strain were enriched for the regulation of bone marrow microenvironment pathways,those of low-susceptible strain were enriched for the proapoptotic effect of GTPase pathways.Based on protein abundance differences,several urinary proteins that may be indicative of susceptibility were screened,and ELISA validation results showed that angiotensin-converting enzyme may be a potential biomarker predicting HSC susceptibility for BU conditioning.Conclusions:This study indicates that urinary protein levels can reflect differences in susceptibility to BU-i nduced HSC injury.Using GD mice to construct genetic difference models will provide preclinical data for screening BU-related biological markers.