Targeting whole body metabolism and mitochondrial bioenergetics in the drug development for Alzheimer's disease

Aging is by far the most prominent risk factor for Alzheimer's disease (AD), and both aging and AD are associated with apparent metabolic alterations. As developing effective therapeutic interventions to treat AD is clearly in urgent need, the impact of modulating whole-body and intracellular metabolism in preclinical models and in human patients, on disease pathogenesis, have been explored. There is also an increasing awareness of differential risk and potential targeting strategies related to biological sex, microbiome, and circadian regulation. As a major part of intracellular metabolism, mitochondrial bioenergetics, mitochondrial quality-control mechanisms, and mitochondria-linked inflammatory responses have been considered for AD therapeutic interventions. This review summarizes and highlights these efforts.

Levels of angiotensin-converting enzyme 1 and 2 in serum and urine of children with Sickle Cell Disease / Níveis de enzima conversora da angiotensina 1 e 2 no soro e na urina de crianças com Doença Falciforme

Abstract Introduction: Sickle cell nephropathy begins in childhood and presents early increases in glomerular filtration, which, over the long term, can lead to chronic renal failure. Several diseases have increased circulating and urinary angiotensin-converting enzyme (ACE) activity, but there is little information about changes in ACEs activity in children with sickle cell disease (SCD). Objective: We examined circulating and urinary ACE 1 activity in children with SCD. Methods: This cross-sectional study compared children who were carriers of SCD with children who comprised a control group (CG). Serum and urinary activities of ACE were evaluated, as were biochemical factors, urinary album/creatinine rates, and estimated glomerular filtration rate. Results: Urinary ACE activity was significantly higher in patients with SCD than in healthy children (median 0.01; range 0.00-0.07 vs median 0.00; range 0.00-0.01 mU/mL·creatinine, p < 0.001. No significant difference in serum ACE activities between the SCD and CG groups was observed (median 32.25; range 16.2-59.3 vs median 40.9; range 18.0-53.4) mU/m`L·creatinine, p < 0.05. Conclusion: Our data revealed a high urinary ACE 1 activity, different than plasmatic level, in SCD patients suggesting a dissociation between the intrarenal and systemic RAAS. The increase of urinary ACE 1 activity in SCD patients suggests higher levels of Ang II with a predominance of classical RAAS axis, that can induce kidney damage.

Resumo Introdução: A nefropatia falciforme começa na infância e apresenta aumentos precoces na filtração glomerular, que, em longo prazo, podem levar à insuficiência renal crônica. Várias doenças têm aumentado a atividade da enzima conversora da angiotensina (ECA) urinária e circulante, mas há pouca informação sobre alterações na atividade das ECAs em crianças com doença falciforme (DF). Objetivo: Examinamos a atividade da ECA-1 circulante e urinária em crianças com DF. Métodos: Este estudo transversal comparou crianças que eram portadoras de DF com crianças que compunham um Grupo Controle (GC). As atividades séricas e urinárias da ECA foram avaliadas, assim como os fatores bioquímicos, a relação albumina/creatinina urinária e a taxa de filtração glomerular estimada. Resultados: A atividade urinária da ECA foi significativamente maior em pacientes com DF do que em crianças saudáveis (mediana 0,01; intervalo 0,00-0,07 vs mediana 0,00; intervalo 0,00-0,01 mU/mL·creatinina, p < 0,001. Não foi observada diferença significativa nas atividades séricas da ECA entre os grupos DF e GC (mediana 32,25; intervalo 16,2-59,3 vs mediana 40,9; intervalo 18,0-53,4) mU/mL·creatinina, p < 0,05. Conclusão: Nossos dados revelaram uma alta atividade urinária da ECA-1, diferente do nível plasmático, em pacientes com DF, sugerindo uma dissociação entre o Sistema Renina Angiotensina Aldosterona (SRAA) intra-renal e sistêmico. O aumento da atividade urinária da ECA-1 em pacientes com DF sugere níveis mais elevados de Ang II com predominância do eixo clássico do SRAA, que pode induzir lesão renal.

Clinical features and pathogenesis of liver injury caused by SARS, MERS and COVID-19 / 临床肝胆病杂志

Coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 has become a serious threat to global public health security. Besides lung diseases, severe cases are also accompanied by varying degrees of liver injury. Previous studies have shown that patients infected with severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus may also suffer from liver injury, which is closely associated with disease severity. This article elaborates on the clinical features and pathogenesis of liver injury caused by these three types of highly pathogenic human coronavirus, in order to help clinicians better understand this disease and make accurate decisions.

Functional Cell Receptors for Human Coronavirus / 中华检验医学杂志

Viruses infect host cells by binding to receptors on thesurface of cells. Receptor is an important factor affecting host range and interspecific transmission. In December 2019, an outbreak of unexplained pneumonia occurred in Wuhan, Hubei province. The pathogen was a new coronavirus, named 2019 NovelCoronavirus (2019-nCoV) by WHO. Angiotensin-converting enzyme 2 (ACE2) was found to be the receptor of 2019-nCoV.This review provides a brief overview of human coronavirus receptors and their applications, with a view to providing references for the tracing, cross-species transmission, epidemiological analysis and antiviral and vaccine studies of 2019-nCoV.

Effects of Chronic Exposure to Mercury on Angiotensin-Converting Enzyme Activity and Oxidative Stress in Normotensive and Hypertensive Rats / Efeitos da Exposição Crônica ao Mercúrio sobre a Atividade da Enzima Conversora de Angiotensina e Estresse Oxidativo em Ratos Normotensos e Hipertensos

Abstract Background: Mercury's deleterious effects are associated with increased cardiovascular risk. Objective: To determine whether chronic exposure to inorganic mercury increases the activity of angiotensin-converting enzyme and its relationship with oxidative stress in several organs and tissues. Methods: We studied male Wistar and spontaneously hypertensive rats (SHR) (3-month-old) exposed or not to HgCl2 for 30 days. At the end of treatment, we investigated the following: changes in body weight, hemodynamic parameters, angiotensin-converting enzyme (ACE) activity and oxidative stress in the heart, aorta, lung, brain and kidney in hypertensive compared to normotensive animals. A value of p < 0.05 was considered significant. Results: Chronic exposure to HgCl2 did not affect weight gain in either group. Systolic blood pressure, measured weekly, did not increase in Wistar rats but showed a small increase in SHR rats. We also observed increases in left ventricular end-diastolic pressure and ACE activity in the plasma and hearts of normotensive rats. In the SHR+Hg group, ACE activity increased in plasma but decreased in kidney, lung, heart, brain and aorta. Oxidative stress was assessed indirectly by malondialdehyde (MDA) production, which increased in Hg-treated rats in both plasma and heart. In the SHR+Hg group, MDA increased in heart and aorta and decreased in lungs and brain. Conclusion: These results suggest that chronic exposure to inorganic mercury aggravates hypertension and produces more expressive changes in ACE activity and oxidative stress in SHRs. Such exposure affects the cardiovascular system, representing a risk factor for the development of cardiovascular disorders in normotensive rats and worsening of pre-existing risks for hypertension.

Resumo Fundamento: Os efeitos deletérios do mercúrio estão associados ao risco cardiovascular aumentado. Objetivo: Determinar se a exposição crônica ao mercúrio inorgânico aumenta a atividade da enzima conversora de angiotensina e sua relação com o estresse oxidativo em vários órgãos e tecidos. Métodos: Estudamos ratos Wistar e ratos espontaneamente hipertensos (SHR) (3 meses de idade) expostos ou não a HgCl2 por 30 dias. Ao final do tratamento, investigamos: alterações de peso, parâmetros hemodinâmicos, atividade da enzima conversora de angiotensina (ECA) e estresse oxidativo no coração, aorta, pulmão, cérebro e rim de animais hipertensos comparados a animais normotensos. Um valor de p < 0,05 foi considerado significativo. Resultados: A exposição crônica ao HgCl2 não afetou o ganho de peso em nenhum dos grupos. A pressão arterial sistólica, medida semanalmente, não aumentou em ratos Wistar, mas mostrou um pequeno aumento nos ratos SHR. Também observamos aumentos na pressão diastólica final do ventrículo esquerdo e na atividade da ECA no plasma e no coração de ratos normotensos. No grupo SHR + Hg, a atividade da ECA aumentou no plasma, mas diminuiu no rim, pulmão, coração, cérebro e aorta. O estresse oxidativo foi avaliado indiretamente pela produção de MDA, que aumentou nos ratos tratados com Hg tanto no plasma quanto no coração. No grupo SHR + Hg, o MDA aumentou no coração e na aorta e diminuiu nos pulmões e no cérebro. Conclusão: Estes resultados sugerem que a exposição crônica ao mercúrio inorgânico agrava a hipertensão e produz mudanças mais expressivas na atividade da ECA e no estresse oxidativo em SHRs. Essa exposição afeta o sistema cardiovascular, representando um fator de risco para o desenvolvimento de distúrbios cardiovasculares em ratos normotensos e para piorar riscos pré-existentes para hipertensão.

Relationship between insertion/deletion polymorphism of angiotensin converting enzyme gene and type 2 diabetic kidney disease / 中华检验医学杂志

Objective To explore the interaction of angiotensin converting enzyme (ACE) insertion/deletion(I/D) polymorphism(rs1799752)with diabetic kidney disease (DKD) development as well as its interaction with smoking and obesity in Chinese type 2 diabetic mellitus (T2DM) using the improved experiment method. Methods From June 2016 to March 2018, 300 T2DM patients with DKD [DKD(+)] and 300 T2DM patients without DKD[DKD(-)] were selected from China-Japan Friendship Hospital. The improved Triple Primer Method that combined PCR with capillary electrophoresis was established in this study to detect the ACE genotype. The relevant clinical data as well as the frequencies of genotype and allele of ACE gene I/D polymorphism between two groups were statistically analyzed. Patients were further grouped based on smoking status and obesity for multivariate regression. Results Frequency of the DD genotype and D allele were significantly higher in DKD(+) group than in DKD(-) group [DD genotype:15.0％ (45 cases) vs 7.3％(22 cases),χ2=10.8, P=0.004;D allele:36.5％(219 cases) vs 28.0％(168 cases),χ2=9.92, P=0.02]. Multivariate logistic regression analysis found that D allele of rs1799752 was associated with a significantly higher risk of DKD in both recessive model(OR=1.45, 95％CI:1.06-2.00, P=0.022 after adjustments) and additive model(OR=1.41, 95％CI:1.04-1.90, P=0.025 after adjustments). In the smoker group and the obese group, D allele showed significant relationship with DKD incidence (P<0.05 after adjustments) in both recessive model and dominant model. No such relationships were observed in non-smoker group and non-obese group (P>0.05). Conclusions I/D polymorphism of ACE gene is associated with the incidence of DKD in T2DM patients. DD genotype of the ACE gene is the risk factor for T2DM patients with DKD. D allele may increase DKD incidence in the presence of smoking and obesity.

Is serum angiotensin converting enzyme level a useful non-invasive marker for liver fibrosis in patients with chronic hepatitis C?

Summary Objective: Chronic hepatitis C (CHC) continues to be a critical problem. The liver fibrosis score is the most valuable tool in determining treatment and prognosis. Liver biopsy is still considered a gold method but, due to unmet needs, new non-invasive markers are required. The aim of this study was to investigate any possible relationship between serum angiotensin-converting enzyme (ACE) levels and the stages of liver fibrosis in patients with CHC. Method: A total 100 CHC and 100 healthy subjects were enrolled in this study. The relationship between serum ACE level and the stages liver fibrosis was investigated using three different formats, as follows: (group [G]-I, classic Ishak's Score from F1 to F6; G-II, mild [F1-2], moderate [F3-4] and severe [F5-6]; G-III, mild [≤ F2] and advanced [F > 2]). The clinical usability of serum ACE level for both groups was also investigated. Results: Median serum ACE levels were higher in the healthy group than in CHC (42.5 [7-119] vs. 36 [7-91] U/I, p=0.002). There was no statistical difference among the three different fibrosis groups (G-I, G-II, G-III, p=0.797, p=0.986, and p=0.874) and no correlation between serum ACE level and the stages of liver fibrosis (r=0.026, p=0.923). The usability of serum ACE for evaluated patients with CHC and healthy subjects were calculated as 47% and 64%, respectively. Conclusion: Our study indicated that there is no relationship or correlation between serum ACE levels and stages of liver fibrosis in patients with CHC. The assessment of serum ACE level using genetically corrected reference values may provide more accurate results.

Effect of angiotension-converting enzyme gene polymorphism on dexmedetomidine-induced inhibition of responses to extubation in patients with hypertension / 中华麻醉学杂志

Objective To evaluate the effect of angiotension-converting enzyme (ACE) gene poly-morphism on dexmedetomidine-induced inhibition of responses to extubation in the patients with hyperten-sion. Methods A total of 180 patients with primary hypertension, aged 50-63 yr, weighing 54-69 kg, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, scheduled for elective abdominal surgery under general anesthesia, in whom ACE genotypes were detected using polymerase chain reaction-restriction fragment length polymorphism, were divided into 6 groups (n = 30 each) according to whether dexmedeto-midine was applied: DD genotype group (DD group), ID genotype group (ID group), Ⅱ genotype group (Ⅱ group), dexmedetomidine +DD genotype group (DEX+DD group), dexmedetomidine +ID genotype group (DEX+ID group) and dexmedetomidine+Ⅱ genotype group ( DEX+Ⅱ group). Dexmedetomidine 0. 5 μg·kg-1 ·h-1 was intravenously infused starting from 30 min before the end of surgery until the end of surgery in DEX+DD, DEX+ID and DEX+Ⅱ groups. Immediately before infusing dexmedetomidine (T1 ), at 30 min of dexmedetomidine infusion (T2 ), immediately after extubation (T3 ) and at 1. 5, 5 and 15 min after extubation (T4-6 ), systolic blood pressure, diastolic blood pressure, heart rate and ECG were recor-ded, and rate-pressure product was calculated. The development of myocardial ischemia and responses to extubation was recorded within 15 min after extubation. Results Compared with the baseline at T1 , each parameter of hemodynamics was significantly increased at T3-6 in DD, ID and Ⅱ groups (P<0. 05), and no significant change was found in each parameter of hemodynamics at T2-6 in Dex+DD, Dex+ID and Dex+Ⅱ groups (P> 0. 05). Each parameter of hemodynamics was significantly lower at T3-6 , and the inci-dence of myocardial ischemia and responses to extubation was decreased in group Dex+DD than in group DD and in group Dex+ID than in group ID (P<0. 05). Compared with group Ⅱ, each parameter of he-modynamics at T3-6 and incidence of responses to extubation were significantly decreased in group Dex+Ⅱ, and each parameter of hemodynamics was significantly increased at T3-6 , and the incidence of myocardial ischemia and responses to extubation was increased in DD and ID groups (P<0. 05). There was no signif-icant difference in each parameter of hemodynamics or incidence of myocardial ischemia and responses to extubation among group Dex+DD, group Dex+ID and group Dex+I (P>0. 05). Conclusion ACE gene polymorphism does not affect dexmedetomidine-induced inhibition of responses to extubation in the patients with hypertension.

Association of actn3 r577x and ace i/d polymorphisms in brazilians wrestlers / Associação dos polimorfismos actn3 r577x e ace i/d em lutadores brasileiros / Asociación de los polimorfismos actn3 r577x y ace i/d en luchadores brasileños

ABSTRACT Introduction: By associating genetics and sport, it is possible to identify subjects with greater capacity to adapt to training, and lower chances of injury. Objective: The investigation evaluated the genotypic and allelic distribution of ACTN3 R577X and ACE I/D polymorphisms in Brazilian high-performance athletes in wrestling and percussion combat sports. Methods: The study included 37 male athletes ranked from first to third place in world scenarios, divided into two groups: wrestling (23 wrestlers, being 11 of Judo, 4 of Greco-Roman style, 8 of Brazilian Jiu Jitsu, with mean age of 27.3 ± 6.9 years) and percussion combat sports (14 athletes with a mean age of 25.7±4.4 years, being 6 of Karate, 3 of Muay Thai, 4 of Taekwondo, 1 Boxing). Genotyping of ACTN3 and ACE I/D polymorphisms was performed by polymerase chain reaction (PCR) from the genomic DNA. Genotypic and allelic distributions were compared with control populations and athletes by Chi-square test and Fisher's exact test; all analyzes considered p ≤ 0.05. Results: The genotypic distributions and allelic frequencies of ACTN3 RR=46%, RX=38% and XX=16%; R=65% and X=35%, and ACE I/D DD=47.7%, ID=34.3% and II=20%; D=62.9% and I=37.1% did not differ from the control population; however, when compared with wrestling athletes a significant difference was observed. Conclusion: These results suggest an association of ACTN3 R577X and ACE I/D genes with Brazilian high-performance wrestling athletes.

RESUMO Introdução: Ao associar genética e esporte, existe a possibilidade de identificar sujeitos com maior capacidade de adaptação ao treinamento com menores chances de lesões. Objetivo: A investigação avaliou a distribuição genotípica e alélica dos polimorfismos ACTN3 R577X e ACE I/D em lutadores de domínio e percussão de alto rendimento brasileiros. Métodos: Participaram do estudo 37 atletas do sexo masculino, colocados de primeiro a terceiro lugar nos cenários mundiais, divididos em dois grupos: domínio (23 lutadores sendo 11 de judô, 4 de luta greco-romana, 8 de jiu-jitsu brasileiro; a média de idade foi 27,3 ± 6,9 anos) e percussão (14 atletas com média de idade de 25,7 ± 4,4 anos sendo 6 de caratê, 3 de muay thai, 4 de taekwondo, 1 de boxe). A genotipagem dos polimorfismos do ACTN3 e ACE I/D foi realizada por reação em cadeia da polimerase (PCR) a partir do DNA genômico. As distribuições genotípicas e alélicas foram comparadas com populações controle e de atletas pelos testes do qui-quadrado e exato de Fisher; todas as análises consideraram p ≤ 0,05. Resultados: As distribuições genotípicas e frequências alélicas do ACTN3 RR=46%, RX=38% e XX=16%; R=65% e X=35% e ACE I/D DD=47,7%, ID=34,3% e II=20%; D=62,9% e I=37,1% não diferiram da população controle, porém, quando comparadas com atletas de luta, constatou-se diferença significativa. Conclusão: Esses resultados sugerem uma associação dos genes ACTN3 R577X e ACE I/D aos lutadores de domínio de alto rendimento brasileiros.

RESUMEN Introducción: Al asociar genética y deporte, existe la posibilidad de identificar sujetos con mayor capacidad de adaptación a los entrenamientos con menores posibilidades de lesión. Objetivo: La investigación evaluó la distribución genotípica y alélica de los polimorfismos ACTN3 R577X y ACE I/D en luchadores brasileños de alto rendimiento de técnicas de agarre y golpeo. Métodos: Participaron en el estudio 37 atletas del sexo masculino, colocados de primer a tercer lugar en escenarios mundiales, divididos en dos grupos: agarre (23 luchadores, siendo 11 de judo, 4 de lucha grecorromana y 8 de jiu-jitsu; el promedio de edad fue de 27,3 ± 6,9 años) y golpeo (14 atletas con promedio de edad de 25,7 ± 4,4 años, siendo 6 de karate, 3 de muay-thai, 4 de taekwondo y 1 de boxeo). El genotipado de los polimorfismos de ACTN3 y ACE I/D se llevó a cabo por reacción en cadena de la polimerasa (PCR) a partir de ADN genómico. Las distribuciones genotípicas y alélicas fueron comparadas con poblaciones control y atletas por las pruebas del chi-cuadrado y exacta de Fisher; todos los análisis consideraron p ≤ 0,05. Resultados: Las distribuciones de los genotipos y frecuencias alélicas de ACTN3 RR=46%, RX=38% y XX=16%; R=65% y X=35% y ACE I/D DD=47,7%, ID=34,3% e II=20%; D=62,9% e I=37,1% no difirieron de la población control, sin embargo, cuando comparadas con los atletas de lucha, se constató diferencia significativa. Conclusión: Estos resultados sugieren una asociación de los genes ACTN3 R577X y ACE I/D a los luchadores brasileños de alto rendimiento de técnicas de agarre.

Pericardial Parietal Mesothelial Cells: Source of the Angiotensin-Converting-Enzyme of the Bovine Pericardial Fluid / Células Mesoteliais Pericárdicas Parietais: Fonte da Enzima Conversora de Angiotensina Existente no Líquido Pericárdico Bovino

Abstract Background: Angiotensin II (Ang II), the primary effector hormone of the renin-angiotensin system (RAS), acts systemically or locally, being produced by the action of angiotensin-converting-enzyme (ACE) on angiotensin I. Although several tissue RASs, such as cardiac RAS, have been described, little is known about the presence of an RAS in the pericardial fluid and its possible sources. Locally produced Ang II has paracrine and autocrine effects, inducing left ventricular hypertrophy, fibrosis, heart failure and cardiac dysfunction. Because of the difficulties inherent in human pericardial fluid collection, appropriate experimental models are useful to obtain data regarding the characteristics of the pericardial fluid and surrounding tissues. Objectives: To evidence the presence of constituents of the Ang II production paths in bovine pericardial fluid and parietal pericardium. Methods: Albumin-free crude extracts of bovine pericardial fluid, immunoprecipitated with anti-ACE antibody, were submitted to electrophoresis (SDS-PAGE) and gels stained with coomassie blue. Duplicates of gels were probed with anti-ACE antibody. In the pericardial membranes, ACE was detected by use of immunofluorescence. Results: Immunodetection on nitrocellulose membranes showed a 146-KDa ACE isoform in the bovine pericardial fluid. On the pericardial membrane sections, ACE was immunolocalized in the mesothelial layer. Conclusions: The ACE isoform in the bovine pericardial fluid and parietal pericardium should account at least partially for the production of Ang II in the pericardial space, and should be considered when assessing the cardiac RAS.

Resumo Fundamentos: Angiotensina II (Ang II), o hormônio efetor primário do sistema renina-angiotensina (SRA), atuando em níveis sistêmicos ou locais, é produzida pela ação da enzima conversora de angiotensina (ECA) sobre a angiotensina I. Embora diversos SRAs teciduais, como o SRA cardíaco, tenham sido descritos em muitos estudos, dados de um SRA no líquido pericárdico e sua origem não são ainda disponíveis. A Ang II localmente produzida tem efeitos parácrinos e autócrinos, induzindo a hipertrofia ventricular esquerda, fibrose, insuficiência e disfunção cardíacas. Devido às dificuldades inerentes à obtenção de líquido pericárdico humano, modelos experimentais apropriados são muito úteis para obter dados relativos às suas características bem como dos tecidos contíguos. Objetivos: Obter evidências da presença de constituintes das vias de produção de Ang II no líquido pericárdico e no pericárdio parietal bovinos. Métodos: Extratos brutos de líquido pericárdico bovino sem albumina (sobrenadantes), imunoprecipitados com anticorpo anti-ECA, foram submetidos a eletroforese (SDS-PAGE) e os géis corados com Coomassie Blue. Duplicatas dos géis foram sondadas com anticorpo anti-ECA. A detecção de ECA nas membranas pericárdicas foi realizada por imunofluorescência. Resultados: A imunodetecção sobre as membranas de nitrocelulose mostrou uma isoforma de ECA com 146 KDa no líquido pericárdico bovino. Nas secções de membrana pericárdica, a ECA foi imunolocalizada na camada mesotelial. Conclusões: A isoforma de ECA do líquido pericárdico bovino e do pericárdio parietal deve ser, pelo menos em parte, responsável pela produção de Ang II no espaço pericárdico, devendo ser considerada quando o SRA cardíaco for avaliado.

Meta analysis on ACE I/D gene polymorphism and migraine / 重庆医学

Objective To investigate the association between the angiotensin-converting enzyme (ACE) I/D locus polymor-phism and migraine susceptibility .Methods The case control studies on the relation between ACE I/D gene polymorphism and mi-graine susceptibility published in the databases of PubMed and EMBAE were retrieved .The relationship between ACE 1/D poly-morphism and migraine was evaluated through the effect size (OR) and 95% confidence interval(CI) by fixed-effects model or ran-dom-effect models .Meanwhile the subgroup analysis of ethnicity and migraine types was performed .Results In meta analysis ,the homozygote model(DD vs .Ⅱ:OR= 1 .21 ,95% CI:1 .02-1 .44 ,P=0 .03 ;I2 =47% ) and dominant model all indicated that the ACE I/D polymorphism was positively correlated with the susceptibility of all migraine .The heterozygote model (DI vs .Ⅱ:OR=1 .35 , 95% CI:1 .06-1 .72 ,P=0 .02 ;I2 =10% ) and dominant model (DD+DI vs .Ⅱ:OR=1 .37 ,95% CI:1 .09 -1 .73 ,P=0 .00 ;I2 =40% ) indicated that ACE I/D polymorphism significantly increased the susceptibility of migraine with aura .Conclusion The ACE I/D locus polymorphism is correlated with migraine susceptibility ,its D allele is a risk factor of migraine ,which especially increases the susceptibility of migraine with aura .

A Meta-analysis of the relationship between ACE gene L/D polymorphism and vitiligo / 中国医师杂志

Objective To investigate the relationship of angiotensin converting enzyme (ACE I/D) gene I/D polymorphism with vitiligo.Methods PubMed,the Cochrane Library,China academic journal full-text database and VIP database and Wan fang database were searched according to the inclusion and exclusion criteria,and the quality of included studies was assessed.The data were quantitatively analyzed by Stata 12.0 software.Results Nine articles were included.Meta analysis results showed that the susceptibility of vitiligo difference was statistically significant in the total population of ACE I/D genotype (DD + II)vs.DI (OR=0.759,95％ CI:0.643 ～0.896,P=0.001),the (DD+DI) vs.II (OR=1.523,95％ CI:1.153 ～2.011,P =0.003).The genotype subgroup analysis showed the D vs.I (OR =1.381,95％ CI:1.054 ～1.810,P=0.019),DDvs.II (OR=1.830,95％ CI:1.110～3.017,P=0.018),(DD+ II) vs.DI (OR=0.814,95％ CI:0.667 ～0.994,P=0.043),and the (DD+ID) vs.II (OR=1.690,95％ CI:1.147 ～2.489,P =0.008) in Asian.The difference was statistically significantly related to vitiligo.Arab genotype (DD + II) vs.DI (OR =0.545,95％ CI:0.354 ～ 0.840,P =0.006) was associated with vitiligo occurrence.Begg's inspection publication bias analysis showed all genetic types did not exist any publication bias.Conclusions The ACE gene I/D polymorphism may be associated with vitiligo susceptibility.

Effects of paeonol on RAS occurred on the development of ventricular remodeling after acute myocardial infarction in rats / 天津医药

Objective To investigate the effects of paeonol on renin-angiotensin system (RAS) occurred on the development of ventricular remodeling after acute myocardial infarction (AMI) in rats. Methods The left anterior descending coronary artery was ligated to establish the model of AMI in male SD rats. Six groups were set up:sham-operation group, AMI model group, captopril control group, paeonol low dose group (6 mg/kg), paeonol middle dose group (9 mg/kg) and paeonol high dose group (12 mg/kg). Rats were given treatment for 4 weeks after the AMI model was established. HE staining was used to observe changes of myocardial tissue. Real-time PCR was used to detect the mRNA levels of angiotensinogen (AGT), angiotensin Ⅱ receptor type1(AGTR1) and endothelin (ET)-1 of six groups. Western blot assay was used to detect the protein levels of peptidyl-dipeptidase A (ACE), angiotensin Ⅱ(Ang)-Ⅱand AGTR1 in six groups. Results The transcription of AGT, AGTR1, ET-1mRNA and the expressions of ACE, Ang-Ⅱ and AGTR1 protein were significantly higher in myocardial tissue of AMI rats than those of sham-operation rats (P＜0.05). Compared with model group, the expressions of AGT, AGTR1, ET-1mRNA and ACE, Ang-Ⅱ, AGTR1 protein were significantly decreased in paeonol high dose group and captopril control group (P＜0.05). Paeonol reduced the expressions of those mRNA and protein levels in a significant dose dependent manner. Conclusion Paeonol can slow down the deterioration of the ventricular remodeling after AMI in rats, which may be related to the inhibition of over-activation of RAS.

Survival and Predictive Factors of Lethality in Hemodyalisis: D/I Polymorphism of The Angiotensin I-Converting Enzyme and of the Angiotensinogen M235T Genes / Sobrevida e Fatores Preditores de Letalidade em Hemodiálise: Polimorfismos D/I do Gene da Enzima Conversora da Angiotensina I e o M235T do Angiotensinogênio

Background: End-stage kidney disease patients continue to have markedly increased cardiovascular disease morbidity and mortality. Analysis of genetic factors connected with the renin-angiotensin system that influences the survival of the patients with end-stage kidney disease supports the ongoing search for improved outcomes. Objective: To assess survival and its association with the polymorphism of renin-angiotensin system genes: angiotensin I-converting enzyme insertion/deletion and angiotensinogen M235T in patients undergoing hemodialysis. Methods: Our study was designed to examine the role of renin-angiotensin system genes. It was an observational study. We analyzed 473 chronic hemodialysis patients in four dialysis units in the state of Rio de Janeiro. Survival rates were calculated by the Kaplan-Meier method and the differences between the curves were evaluated by Tarone-Ware, Peto-Prentice, and log rank tests. We also used logistic regression analysis and the multinomial model. A p value ≤ 0.05 was considered to be statistically significant. The local medical ethics committee gave their approval to this study. Results: The mean age of patients was 45.8 years old. The overall survival rate was 48% at 11 years. The major causes of death were cardiovascular diseases (34%) and infections (15%). Logistic regression analysis found statistical significance for the following variables: age (p = 0.000038), TT angiotensinogen (p = 0.08261), and family income greater than five times the minimum wage (p = 0.03089), the latter being a protective factor. Conclusions: The survival of hemodialysis patients is likely to be influenced by the TT of the angiotensinogen M235T gene. .

Fundamento: Os pacientes em hemodiálise continuam tendo um significativo aumento na morbiletalidade, especialmente a causada por doenças cardiovasculares. A análise dos fatores genéticos ligados ao sistema renina-angiotensina que influenciam na sobrevivência destes pacientes poderá ajudar na busca por melhores resultados. Objetivo: Avaliar a sobrevida em hemodialisados e sua associação com polimorfismo dos genes do sistema reninaangiotensina: deleção/inserção do gene que codifica a enzima conversora da angiotensina I e o M235T do angiotensinogênio. Métodos: Estudo observacional desenhado para ver o papel dos genes do sistema renina-angiotensina. Foram analisados 473 pacientes tratados com hemodiálise crônica em quatro unidades de diálise do Estado do Rio de Janeiro. As taxas de sobrevida foram calculadas pelo método de Kaplan-Meier e as diferenças entre as curvas avaliadas pelos testes de: Tarone-Ware, Peto-Prentice e Log-rank. Foram utilizados também modelos de regressão logística e multinomial. Um valor de p ≤ 0,05 foi considerado estatisticamente significativo. O comitê de ética aprovou este estudo. Resultados: A idade média dos pacientes foi de 45,8%. A taxa de sobrevida global foi de 48% em 11 anos. As principais causas de óbito foram: doenças do aparelho circulatório (34 %) e infecções (15%). A análise de regressão logística encontrou significância estatística para as seguintes variáveis: idade, o TT do angiotensinogênio e a renda familiar acima de cinco salários mínimos, esta última como fator de proteção (p valor: 0,000038, 0,08261 e 0,03089, respectivamente). Conclusões: Nossos dados sugerem que o risco de letalidade em pacientes em hemodiálise pode ser influenciado também pelo polimorfismo ...

The association between angiotensin converting enzyme gene polymorphism and Alzheimer’s disease in Jiamusi region / 中国组织工程研究

BACKGROUND:Angiotensin-converting enzyme as a key enzyme of the renin-angiotensin system, through the degradation effects of substance P mechanism, is involved in the occurrence and development of Alzheimer’s disease. OBJECTIVE:To research the relationship between angiotensin-converting enzyme gene polymorphism and Alzheimer’s disease in Jiamusi region, as wel as the effect of gender and hypertension on the relationship. METHODS:This case-control study included 96 Alzheimer’s disease patients. Another 102 subjects served as controls coming from the same area and in the same environmental condition. DNA segments were amplified using PCR in 20 g/L agarose gel electrophoresis and observed under ultraviolet lamp. II, ID, DD genotypes and genotype frequencies were calculated for statistical analysis. On this basis, according to clinical data col ected, we investigated association of Alzheimer’s disease with hypertension and gender. RESULTS AND CONCLUSION:There was significant difference between Alzheimer’s disease patients and controls in angiotensin-converting enzyme genotypes and al ele frequency. There was statistical y significant difference between Alzheimer’s patients with hypertension and controls in angiotensin-converting enzyme genotypes and al ele frequency. There was no statistical difference between Alzheimer’s disease patients with different genders and controls in angiotensin-converting enzyme genotypes and al ele frequency. These findings indicate that there are some relationships between angiotensin-converting enzyme polymorphism and Alzheimer’s disease. II genotype is a risk factor for Alzheimer’s disease, angiotensin-converting enzyme II genotype is a risk factor for Alzheimer’s disease with hypertension.

The changes of atrial muscle RAS and ACE2-Ang(1-7)-Mas axis in MODS dogs treated by CVVHDF and the mechanism / 中华肾脏病杂志

Objective To observe the members' dynamic change of renin-angiotensin system (RAS) and angiotensin converting enzyme 2(ACE2)-Ang(1-7)-Mas axis during the continuous venovenous hemodiafiltration (CVVHDF) treating the dogs with multiple organ dysfunction syndrome (MODS),and to investigate the efficacy mechanism on cardiac function.Methods Dogs were subjected to hemorrhagic shock plus resuscitation and endotoxemia to establish MODS model,then they were randomly divided into 2 groups:CVVHDF group (n=8) and MODS group (n=6).After endotoxin injection completion,the CVVHDF group received CVVHDF for 12 h,MODS group didn't.Radioimmunoassay,euzymelinked mmunosorbent assay (ELISA) were used to detect the content of renin,Ang Ⅰ,Ang Ⅱ,Ang (1-7).Real-time PCR was used to detect the expression of renin mRNA and ACE2 mRNA.Western blotting was used to detect the protein content of renin,Ang Ⅱ,ACE2 and Ang (1-7).Results (1) Organ function:Compared with the MODS group,the vital signs,heart,lung and renal function were significantly ameliorated in the CVVHDF group,the difference had statistical significance (P＜ 0.05).(2) RAS changes:To detect index from the level of organs,genetic and molecular in arterial tissue,the results displayed that the content of renin,Ang Ⅰ,Ang Ⅱ,the expression of renin mRNA,the protein content of renin,Ang Ⅱ in CVVHDF group were lower than that in MODS group,the difference had statistical significance (P ＜ 0.01).(3)ACE2-Ang(1-7)-Mas axis's changes:Using the same methods above to detect corresponding indicators,the results displayed that the content of ACE2,Ang(1-7),the expression of ACE2 mRNA and the protein content of ACE2,Ang(1-7) in CVVHDF group were significantly improved than that in MODS group,the difference had statistical significance (P ＜ 0.01).Conclusions In the process of CVVHDF treating MODS,the ACE2 -Ang(1-7)-Mas axis plays the role which antagonizes the RAS system,and to protect the cardiac function.This research may be important for MODS' clinical rescue.

Analysis on the situation of angiotensin-converting enzyme gene polymorphism in military service officers of Jinan theater / 重庆医学

Objective To investigate and analysis the situation of angiotensin-converting enzyme (ACE) gene polymorphism in military service officers of Jinan theater .Methods Roche Cycler480II fluorescence quantitative PCR analyzer was used to detected ACE genotype .Meanwhile ,some samples were randomly analyzed by agarose gel electrophoresis .Results ACE DD genotype ac-counted for 23 .3% in the military service officers of Jinan theater cadres ,ID type accounted for 43 .2% ,II type accounted for 33 .5% ,D and I allele frequencies were 0 .44 and 0 .56 ,respectively ;type II ACE gene frequency was highest in female cadres ,while frequency of ID type was highest in male cadres ,the difference was statistically significant between two groups (P0 .05) .Conclusion ACE gene polymor-phism with type II and Iallele were dominant in the military service officers of Jinan theater cadres ;ACE gene polymorphism survey is important for early detection and timely prevention of certain related diseases .