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Changes of chymase,angiotensin converting enzyme and angiotensin Ⅱ type 1 receptor expressions in the hamster heart during the development of heart failure

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Chinese Medical Journal 2005年第22期118卷 1886-1892页

作者： CHEN Peng-min LENG Xi-gang FAN Li-li MA Jun WANG Ya-fang CHEN Lan-ying Department of Biochemistry Institute of Clinical Medicine China-Japan Friendship Hospital Beijing 100029 Department of Biochemistry Fuwai Hospital and CardiovascularInstitute Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100037 China Department of Biochemistry Institute of Biomedical EngineeringChinese Academy of Medical Sciences and Peking Union Medical College Tianjin 300192 China Department of Pharmacology Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050 China

Background Little is known about the role of dual angiotensin Ⅱ forming pathways during heart failure. In the present study, the changes of chymase and angiotensin converting enzyme （ACE） expressions in the failing hearts of hamsters were analysed. Methods Heart failure was induced by ligation of left anterior descending branch of the coronary artery. Chymase, ACE and angiotensin Ⅱ type 1 receptor （AT1R） mRNA levels were analysed by reverse transcription polymerase chain reaction （RT-PCR）. The activities of chymase and ACE were determined by radioimmunoassay （RIA）. Myocardial collagen fibre analysis was performed under optical microscope. Results Left ventricular systolic pressure （LVSP） and maximum left ventricular developed pressure increase rate （ dp/dtmax, mmHg/s） gradually moved lower at 2, 3,4 and 8 weeks after operation. On the other hand, left ventricular end-diastolic pressure （LVEDP） increased gradually after operation. Compared with the control group （3.55±0. 06, 4.79±0.70）, the heart weight/body weight ratio in operation group had increased significantly at 4 weeks and 8 weeks （4. 28±0. 43, 6. 17±0.73）（P 〈0. 01 ）. Collagen staining showed that the quantity of myocardial collagen fibre increased significantly in the operation group. RT-PCR showed that the chymase mRNA level in the operation group was consistently greater than that in the control group. ATIR mRNA level was also increased significantly at 3 weeks and 4 weeks, both being 1.3 times that of the control group （ P〈0.01 ）, whereas ACE mRNA level was not changed. Higher activity of chymase was detected in operation group, being 4, 8, 13 and 19 times that of the control group at 2, 3, 4 and 8 weeks （P〈0.01 ）, respectively. ACE activity was also significantly higher at the same time, being 7, 10, 10 and 3.5 times that of the control（P〈0.01）. angiotensin Ⅱ （Ang Ⅱ） level in operation group increased significantly, being 2.5, 2.7, 3.5 and 2 times that of the control group at 2, 3, 4 and 8 weeks, respectively （P 〈 0. 01 ）. Conclusions A dual Ang Ⅱ

关键词： chymase angiotensin converting enzyme angiotensin Ⅱ· heart failure ·angiotensin Ⅱ type 1 receptor

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

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World Journal of Gastroenterology 2020年第41期26卷 6335-6345页

作者： Michail Galanopoulos Aris Doukatas Maria Gazouli Department of Gastroenterology 401 General Military Hospital of AthensAthens 11525AttikiGreece Medical Office of Hellenic Army General Staff 401 General Military Hospital of AthensAthens 11525AttikiGreece Laboratory of Biology School of MedicineNational and Kapodistrian University of AthensAthens 11527AttikiGreece

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.

关键词： SARS-CoV-2 COVID-19 Gastrointestinal tract angiotensin converting enzyme type 2 angiotensin converting enzyme type 2 receptor Renin-angiotensin system angiotensin converting enzyme

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Liquid Chromatographic Assay of Peptides Activity with Inhibiting angiotensin converting enzyme

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Chemical Research in Chinese Universities 2010年第5期26卷 712-716页

作者： LIU Jing-bo YU Zhi-peng ZHAO Wen-zhu LU Jing CHEN Feng LIN Song-yi Laboratory of Nutrition and Functional Food Jilin University Changehun 130062 P. R. China Department of Food Science and Human Nutrition Clemson University Clemson SC 29634 USA

A rapid, simple and interference-free method was developed to evaluate the inhibitory activity of hydrolyzed peptides from egg white protein against the angiotensin-converting enzyme. The total reaction volume was 60 μL, saving the cost. The assay was based on a HPLC separation and quantification of the synthetic substrate hippuryl-L-histidyl-L-leucine and its hydrolyzed product-hippuric acid; the separation was performed on a C18 column eluted by a mobile phase of acetonitrile/water（0.5% TFA） at a volume ratio of 25：75. At a signal to noise ratio（S/N） of 10, the detective limit of the quantitation of hippuric acid was （0.4600±0.0097） μmol/L. The standard curve shows a linear response with a slope of 49488 and a correlation coefficient of 0.9995. The assay was adequate for the study of ACE inhibition by Captopril and peptides derived from food protein, and showed a very good correlation with the previous methods.

关键词： angiotensin converting enzyme HPLC Egg white protein Peptide

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Association of angiotensin converting enzyme gene insertion/deletion polymorphism with essential hypertension in south Indian population

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Genes & Diseases 2016年第2期3卷 159-163页

作者： Ramalingam Krishnan Durairaj Sekar Santha karunanithy Sethupathy Subramanium Narayana Medical College and Hospital Nellore605005India Rajamuthaiya Medical College Annamalai UniversityChidhambaram605003India

Genetic,environmental and demographic factors contribute to the development of essential hypertension.Genetic polymorphism of Rennin-angiotensin-aldosterone system(RAAS)has been extensively studied to determine the genetic susceptibility to hypertension.The insertion/deletion(I/D)angiotensin converting enzyme(ACE)polymorphism has been established as a cardiovascular risk factor in some population,but its association with essential hypertension is controversial.This study sought to determine the association of I/D polymorphism of the ACE gene in south Indian essential hypertensive subjects.A total of 208 clinically diagnosed essential hypertensive patients without any associated diseases and 220 healthy control subjects were included in this study.Distribution and allelic frequency of Insertion(I)and Deletion(D)polymorphism at the 287 base pair Alu repeat sequence in the intron 16 of ACE gene were analyzed.The distribution of II,ID,DD genotypes of ACE gene was 28.3%,32.6%and 38.9%respectively in essential hypertensive patients and to 53.6%,26.3%and 20%in controls.The allele frequency for D allele is 0.58 in essential hypertension as compared to 0.34 of control subjects.The genotype and allele frequency of ACE gene polymorphism is significantly differed in patients when compared to controls.In conclusion,the I/D polymorphism of ACE gene is associated with Indian essential hypertension.

关键词： angiotensin converting enzyme Essential hypertension Insertion/deletion polymorphism Renin angiotensin aldosterone system Genotypes

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Mobola plum seed methanolic extracts exhibit mixed type inhibition of angiotensinⅠ-converting enzyme in vitro

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Asian Pacific Journal of Tropical Biomedicine 2017年第12期7卷 1079-1084页

作者： Olamide Olajusi Crown Olanrewaju Sam Olayeriju Ayodele Oluwaseyi Kolawole Afolabi Clement Akinmoladun Mary Tolulope Olaleye Afolabi Akintunde Akindahunsi Department of Biochemistry the Federal University of TechnologyAkureNigeria

Objective: To explore the possible inhibitory potentials and mechanism by Mobola plum(Parinari curatellifolia) seeds crude methanol(CE) and flavonoid-rich(FE) extracts on angiotensin-1-converting enzyme(ACE Ⅰ).Methods: The sensitivity and kinetic model of inhibition of CE and FE on ACE Ⅰ using N-[3-(2-furyl)-acryloyl]-Phe-Gly-Gly as enzyme substrate for ACE Ⅰ was evaluated by Michealis Menten approach. The inhibition mechanism was explored from Lineweaver–Burk model and IC_(50) was determined from Cheng–Prusoff empirical analysis.Results: The IC_(50) of CE and FE were 13.54 and 39.38 mg/m L, respectively. Both extracts exhibited mixed type inhibition with the inhibitory constant(K_i) of CE was between0.38 and 0.37 mg/m L while that of FE showed a two-fold increase(1.62 mg/mL and0.28 mg/mL). FE on ACE Ⅰ demonstrated positive cooperativity with a Hill's coefficient of1.89.Conclusions: The study reveals the superior ACE Ⅰ inhibitory potential of CE over FE and suggest that mixed inhibition pattern of the enzyme might be the underlying mechanism of antihypertensive activity.

关键词： angiotensin converting enzyme Blood pressure FAPGG Mixed type inhibition Parinari curatellifolia

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Hydrolyzates of Silkworm Pupae（Bombyx mori）Protein is a new source of angiotensin I-converting enzyme Inhibitory Peptides（ACEIP）

Hydrolyzates of Silkworm Pupae（Bombyx mori）Protein is a ne...

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中国食品科学技术学会第五届年会暨第四届东西方食品业高层...

作者： Undurti N Das Department of Food Science and Nutrition Zhejiang University Hangzhou310029P.R.China UND Life Sciences13800 Fairhill Road321 Shaker HeightsOH 44120USA

＜正＞Silkworm pupae protein is a good source of high quality protein.The hydrolyzates of silkworm pupae protein catalyzed by neutrase,pepsin,acidic protease（Asperqiius usamii NO. 537）,flavourzyme,alcalase,and trypsin with inhibitory activity on angiotensin I-converting enzyme（ACE）were identified by HPLC.The hydrolyzates catalyzed by acidic protease exerted the highest inhibitory activity on ACE.The hydrolyzing conditions were optimized by one-factor, fractional factorial（FFD）,and center composite（CCD）design methods,and response surface methodology（RSM）.Statistical analyses showed that regression of the second-order model equation is suitable to describe ACE inhibitory bioactivity.The predicted inhibitory activity of hydrolyzates on ACE was 73.48% at a concentration of 2.0 mg/ml.Optimized RSM technique decreased IC50 of hydrolyzates inhibiting ACE to 1.38mg/mL from 2.5mg/ml.The molecular weight of the components of the hydrolyzates with inhibitory activity on ACE varied from 500 to 1000 Da by ultra-filter analysis.These studies suggest that hydrolyzates of silkworm protein contain ACE inhibitory activity that could form a potential source of ACE inhibitor drugs.

关键词： angiotensin converting enzyme silkworm pupae protein Bombyx mori hypertension,hydrolyze

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Potential long-term neurological and gastrointestinal effects of COVID-19:A review of adult cohorts

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World Journal of Methodology 2023年第4期13卷 323-336页

作者： Zaki A Sherif Mrinalini Deverapalli Suryanarayana Reddy Challa Zara Martirosyan Peter Whitesell Antonio Machado Pizuorno Zainab Naqvi Ingrid K Tulloch Gholamreza Oskrochi Hassan Brim Hassan Ashktorab Department of Biochemistry&Molecular Biology Howard University College of MedicineWashingtonDC 20059United States Howard University Cancer Center Howard UniversityWashingtonDC 20060United States Department of Internal Medicine Howard University HospitalWashingtonDC 20060United States Department of Pulmonary Disease/Sleep Medicine Howard University HospitalWashingtonDC 20060United States Department of Internal Medicine The University of Texas Health Science Center at HoustonHoustonTX 77030United States Medical Center Georgetown UniversityWashingtonDC 20007United States Department of Psychology Morgan State UniversityBaltimoreMD 21251United States College of Engineering and Technology American University of the Middle EastKuwait Egaila 54200Kuwait Pathology&Cancer Center Howard University College of MedicineWashingtonDC 20060United States Medicine&Cancer Center Howard University College of MedicineWashingtonDC 20060United States

BACKGROUND The respiratory infection caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has evolved into a multi-organ disorder,with longterm effects known as post-acute sequelae of SARS-CoV-2 infection or long coronavirus disease(COVID).AIM To examine the current knowledge and outcomes of long-term neurological and gastrointestinal(GI)symptoms in adult cohorts,including United States minority populations.METHODS PubMed and Google Scholar were searched using relevant terms,and data from five studies were analyzed,comprising 27383 patients with persistent neurological and GI sequelae.RESULTS The main symptoms included anxiety,depression,dysphagia,headache,vomiting,nausea,gastroesophageal reflux,fatigue,and abdominal pain.Patients with comorbidities and metabolic syndromes were at higher risk for long COVID.While most patients were European Americans,there was a need for further study on African Americans.CONCLUSION The underlying causes of these symptoms remain unclear,warranting more investigation into the long-term impact of the SARS-CoV-2 on different populations.

关键词： angiotensin converting enzyme Long coronavirus disease Post-acute sequalae of SARS-CoV-2 infection Neurological Gastrointestinal Post-viral syndromes

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Diabetes mellitus and COVID-19:Understanding the association in light of current evidence

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World Journal of Clinical Cases 2021年第28期9卷 8327-8339页

作者： Saikat Sen Raja Chakraborty Pratap Kalita Manash Pratim Pathak Faculty of Pharmaceutical Science Assam down town UniversityGuwahati 781026AssamIndia Department of Pharmaceutical Technology School of Medical SciencesADAMAS UniversityKolkata 700126West BengalIndia Department of Pharmacy Pratiksha Institute of Pharmaceutical SciencesGuwahati 781026AssamIndia

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infections have posed a problematic healthcare situation worldwide since December 2019.Diabetes mellitus is associated with an increased risk and severity of coronavirus disease 2019(COVID-19).While interacting with various other risk factors,high blood sugar was found to reduce immunity and increase the replication of SARS�CoV-2.Oxidative stress and the release of pro-inflammatory cytokines are greater in diabetic individuals than in healthy people,worsening the outcome of SARS�CoV-2 infection in diabetics.Increased expression of furin and angiotensin converting enzyme 2(ACE-2)receptor in the hyperglycemic environment may promote the entry of SARS-CoV-2 in the host cell.COVID-19 infection primarily modulates immune and inflammatory responses,and may cause a cytokine storm,resulting in possible lethal outcomes in diabetics.An experimental report suggests that ACE expressed in the pancreas and the SARS-CoV-2 virus invariably destroyβ-cells which contain ACE-2 receptors and results in acute diabetes.Moreover,COVID-19 also causes hyperglycemia in an individual with diabetes which may be related to insulin resistance and destruction ofβ-cells during SARS-CoV-2 infection.Early observations also suggest a correlation between oral hypoglycemic agents and the risk of COVID-19.This review focused on the possible cause and mechanism involved in SARS-CoV-2 infection in diabetics and the role of antidiabetic drugs in COVID-19.

关键词： Diabetes mellitus SARS-CoV-2 COVID-19 angiotensin converting enzyme

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Age and genotype dependent erythropoietin protection in COVID-19

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World Journal of Stem Cells 2021年第10期13卷 1513-1529页

作者： Konstantinos I Papadopoulos Warachaya Sutheesophon Somjate Manipalviratn Tar-Choon Aw Department of Research and Development THAI StemLifeBangkok 10310Thailand Laboratory Department THAI StemLifeBangkok 10310Thailand Department of Reproductive Endocrinology Jetanin Institute for Assisted ReproductionBangkok 10330Thailand Department of Laboratory Medicine Changi General HospitalSingapore 529889Singapore Department of Medicine National University of SingaporeSingapore 119228Singapore

Erythropoietin(EPO)is the main mediator of erythropoiesis and an important tissue protective hormone that appears to mediate an ancestral neuroprotective innate immune response mechanism at an early age.When the young brain is threatened-prematurity,neonatal hyperbilirubinemia,malaria-EPO is hypersecreted disproportionately to any concurrent anemic stimuli.Under eons of severe malarial selection pressure,neuroprotective EPO augmenting genetic determinants such as the various hemoglobinopathies,and the angiotensin converting enzyme(ACE)I/D polymorphism,have been positively selected.When malarial and other cerebral threats abate and the young child survives to adulthood,EPO subsides.Sustained high ACE and angiotensin II(Ang II)levels through the ACE D allele in adulthood may then become detrimental as witnessed by epidemiological studies.The ubiquitous renin angiotensin system(RAS)influences theα-klotho/fibroblast growth factor 23(FGF23)circuitry,and both are interconnected with EPO.Here we propose that at a young age,EPO augmenting genetic determinants through ACE D allele elevated Ang II levels in some or HbE/beta thalassemia in others would increase EPO levels and shield against coronavirus disease 2019,akin to protection from malaria and dengue fever.Human evolution may use ACE2 as a“bait”for severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)to gain cellular entry in order to trigger an ACE/ACE2 imbalance and stimulate EPO hypersecretion using tissue RAS,uncoupled from hemoglobin levels.In subjects without EPO augmenting genetic determinants at any age,ACE2 binding and internalization upon SARS-CoV-2 entry would trigger an ACE/ACE2 imbalance,and Ang II oversecretion leading to protective EPO stimulation.In children,low nasal ACE2 Levels would beneficially augment this imbalance,especially for those without protective genetic determinants.On the other hand,in predisposed adults with the ACE D allele,ACE/ACE2 imbalance,may lead to uncontrolled RAS overactivity and an Ang II induced proinflammatory state

关键词： Erythropoietin angiotensin converting enzyme angiotensin II Hemoglobinopathy Malaria Coronavirus disease 2019 Fibroblast growth factor 23

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Scientific statement of the Chinese Society of Cardiology(CSC) on using of renin angiotensin system blockers in patients with cardiovascular disease and COVID-19

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Journal of Geriatric Cardiology 2020年第5期17卷 241-242页

作者： Ya-Ling HAN Yu-Ming LI Chang-Sheng MA the Editorial Board of Chinese Journal of Cardiology 无不详 the Chinese Society of Cardiology

The coronavirus disease 2019(COVID-19), which is caused by SARS-CoV-2, has become a worldwide public health crisis. Published clinical data from China and other countries have shown a much higher risk of developing COVID-19 and dying from the disease among the elderly, especially among those who had preexisting hypertension, cardiovascular diseases(CVD) and diabetes mellitus[1].

关键词： angiotensin converting enzyme Cardiovascular disease COVID-19 Scientific statement

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