Navegando por Palavras-chave "Angiotensin-converting enzyme"
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- ItemSomente MetadadadosAngiotensin-Converting Enzyme Polymorphism and Erectile Dysfunction Complaints in the Brazilian Population(Wiley-Blackwell, 2010-08-01) Andersen, Monica L. [UNIFESP]; Guindalini, Camila [UNIFESP]; Santos-Silva, Rogerio [UNIFESP]; Bittencourt, Lia R. A. [UNIFESP]; Tufik, Sergio [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Introduction. Angiotensin-converting enzyme (ACE) is the major regulator of circulatory homeostasis. An insertion/deletion (I/D) polymorphism in the ACE gene has been associated with marked differences in serum ACE levels and with various cardiovascular diseases. Limited and conflicting data have been published on the influence of this genetic variant on the pathophysiology of erectile dysfunction (ED).Aim. To evaluate a potential association between ACE gene polymorphism and ED complaints in a population-based sample in So Paulo, Brazil.Main Outcome Measures. the prevalence of ED complaints was estimated according to previously validated 8 item questionnaire.Methods. A total of 449 men were enrolled in the Epidemiologic Sleep Study and answered an 8-item questionnaire to ascertain sexual performance/ED and satisfaction. ACE gene polymorphism were genotyped using a standard polymerase chain reaction method.Results. No significant case control difference was observed for the ACE gene I/D polymorphism either by genotype or allele-wise. Because age is a significant risk factor for ED complaints in our sample, we carried out analyses stratifying the sample by age group. the ID and II genotypes were significantly more frequent in ED complaint cases (88.9%) compared with controls (57.1%) in the men between 40 and 55 years of age. the frequency of the I allele NUS also significantly higher in individuals complaining of Ell (66.7%) compared with men with no complaints (39.0%) (odds ratio = 3.12; 95% confidence interval = 1.48-6.59). Correction for potential confounding variables, including genetic ancestry, did not affect the strength of the association.Conclusions. the findings of the present study suggest that the I/D polymorphism or another variant in close linkage disequilibrium with it may play a role in the development of ED in a specific age group and provides progress towards the understanding of the interaction between genetic factors and the risk of ED. Andersen ML, Guindalini C, Santos-Silva R, Bittencourt LRA, and Tufik S. Angiotensin converting enzyme polymorphism and erectile dysfunction complaints in the Brazilian population. J Sex Med 2010;7:2791-2797.
- ItemAcesso aberto (Open Access)Associação entre as isoformas da ECA e hipertensão arterial sistêmica na segunda fase do estudo prospectivo (projeto MONICA) com a população de Vitória - ES, Brasil(Universidade Federal de São Paulo (UNIFESP), 2017-10-26) Gomes, Andreia Cristina Febba [UNIFESP]; Casarini, Dulce Elena [UNIFESP]; Mill, José Geraldo; http://lattes.cnpq.br/2497419234600362; http://lattes.cnpq.br/0534906942293338; http://lattes.cnpq.br/7657925969818941; Universidade Federal de São Paulo (UNIFESP)A hipertensão é considerada um problema de saúde pública mundial e é o fator de risco de maior impacto para os índices de morbidade e mortalidade cardiovascular. O Sistema Renina Angiotensina (SRA) tem sido foco de interesse dos pesquisadores da área de hipertensão tanto para a identificação de sua etiopatogenia como para o seu tratamento. Com o propósito de identificar os componentes envolvidos no surgimento de hipertensão e a participação da Enzima Conversora de Angiotensina I (ECA) neste problema, o SRA tem sido objeto de muitos estudos. A ECA apresenta grande importância fisiológica por converter a angiotensina I (Ang I) em angiotensina II (Ang II), um potente vasoconstritor. Alguns trabalhos sugerem associação das isoformas da ECA, em especial a isoforma com 90 kDa, com a hipertensão. Este trabalho teve como objetivo geral investigar a associação entre as isoformas da ECA e a presença de hipertensão arterial na segunda fase de estudo prospectivo (Projeto MONICA) na população de Vitória - ES, Brasil. Foram avaliados os parâmetros demográficos, clínicos e bioquímicos de 220 indivíduos. As amostras de urinas foram concentradas e as isoformas da ECA em urina foram identificadas pela técnica de Western Blotting. Os grupos foram classificados como Grupo 1( presença das isoformas com 65, 90 e 190 KDa); Grupo 2 (presença das isoformas com 65 e 90 kDa) e Grupo 3 (presença das isoformas com 65 e 190 kDa). Os resultados mostraram uma alta prevalência da isoforma com 90 kDa com uma incidência de hipertensão (maior no grupo 2), após 5 anos de segmento, os grupos apresentando a isoforma com 90 kDa mostraram perfis de pressão sistólica e diastólica mais elevados na segunda fase e a frequência de normotensos expressando as isoformas com 65 e 190 kDa foi maior em relação à de hipertensos. A perda da expressão da isoforma com 190 kDa, aumenta as chances no desenvolvimento de hipertensão assim como o histórico familiar de hipertensão. Os resultados encontrados sugerem a isoforma N-domínio com 90 kDa como um possível marcador biológico de hipertensão confirmando os dados da primeira fase do estudo.
- ItemSomente MetadadadosAssociation between the angiotensin-converting enzyme (insertion/deletion) and angiotensin II type 1 receptor (A1166C) polymorphisms and breast cancer among Brazilian women(Sage Publications Ltd, 2009-03-01) Corrêa, Silvana Aparecida Alves [UNIFESP]; Noronha, Samuel Marcos Ribeiro de [UNIFESP]; Nogueira-de-Souza, Naiara Corrêa [UNIFESP]; Carvalho, Cristina Valletta de [UNIFESP]; Costa, Ana Maria Massad [UNIFESP]; Linhares, Jose Juvenal [UNIFESP]; Gomes, Mariano Tamura Vieira [UNIFESP]; Silva, Ismael Dale Cotrim Guerreiro da [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Introduction. We evaluated the assocation between components of the renin-angiotensin system and the development of breast cancer in a case-control study by means of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) and angiotensin II type I (AT(1))-receptor A1166C polymorphisms.Methods. Genotyping was performed by PCR-RFLP (restriction fragment length polymorphism) or PCR (polymerase chain reaction) using genomic DNA extracted from buccal cells of subjects with (101 cases) or without (307 controls) breast cancer.Results. the frequencies of genotypes for ACE were: DD, ID and II (in %: cases: 60; 20; 20; controls: 46; 37; 17; p=0.019, chi(2) ); and for AT(1)-receptor were: AA, AC and CC (in %; cases: 65; 30; 5; controls: 51; 44; 5; p=0.114, chi(2)). the results suggested that the A1166C polymorphism was not associated with breast cancer risk. On the other hand, for the ACE (I/D), there seemed to be different risks for cancer between cases and controls.Conclusions. the ID genotype was less frequently associated with the disease than were the DD or II; that is, women with the ID genotype were 3.1 times less likely to develop breast cancer than those with the other genotypes. the ID genotype might be protective against breast cancer and the ACE (I/D) polymorphism a possible targer for developing genetic markers for breast cancer.
- ItemSomente MetadadadosDifferent metabolic responses induced by long-term interdisciplinary therapy in obese adolescents related to ACE I/D polymorphism(Sage Publications Ltd, 2017) Almeida, Sandro Soares [UNIFESP]; Corgosinho, Flavia Campos [UNIFESP]; Amorim, Carlos Eduardo Neves [UNIFESP]; Gregnani, Marcos Fernandes [UNIFESP]; Campos, Raquel Munhoz da Silveira [UNIFESP]; Masquio, Deborah Cristina Landi [UNIFESP]; Sanches, Priscila de Lima [UNIFESP]; Piano, Aline de [UNIFESP]; Pesquero, João Bosco [UNIFESP]; Dâmaso, Ana Raimunda [UNIFESP]; Mello, Marco Tulio de [UNIFESP]; Tufik, Sergio [UNIFESP]; Araujo, Ronaldo de Carvalho [UNIFESP]Introduction: The main purpose of the present study was to investigate whether I/D polymorphism of the ACE gene might affect metabolic changes related to the metabolic syndrome through a long-term interdisciplinary therapy in obese adolescents. Methods: In total, 125 obese adolescents who entered the interdisciplinary obesity programme were assigned to the following two subgroups: metabolic syndrome or non-metabolic syndrome. They were evaluated at baseline and after 1 year. Genomic DNA was extracted from circulating leukocytes. Results: Subjects with the II genotype in the non-metabolic syndrome group were only to increase their fat-free mass after therapy. Regarding lipid profile, subjects with ID and DD genotypes from both groups reduced their low-density lipoprotein cholesterol levels significantly. The metabolic parameters from the ID and DD genotypes of the non-metabolic syndrome group showed a significantly improved insulin response. Conclusion: In the present study, we showed that the ACE polymorphism was able to influence the fat-free mass in the I-carry allele in the non-metabolic syndrome group positively. In addition, the I-carry allele was able to improve the insulin resistance of the metabolic syndrome group significantly. These results suggest that the ACE I/D genotypes can influence, in different ways, the specific parameters of metabolism among obese adolescents submitted for long-term interdisciplinary therapy.
- ItemAcesso aberto (Open Access)Efeito da bradicinina na reatividade vascular sob influência do fenótipo da enzima conversora de angiotensina I (ECA - E.C. 3.4.15.1)(Universidade Federal de São Paulo (UNIFESP), 2017-07-31) Guimarães, Thales Henrique Santos [UNIFESP]; Landman, Maria Teresa Riggio de Lima [UNIFESP]; http://lattes.cnpq.br/8687378770717503; http://lattes.cnpq.br/3147571376928164; Universidade Federal de São Paulo (UNIFESP)In previous studies of the group, it was found that female rats from 2-BAW colony features the plasma angiotensin-converting enzyme (ACE) activity with very outliers, but constant for each animal. This fact made it possible to divide these animals into three groups according to the levels of this enzyme: animals with high ACE activity (ECAa), with intermediate ACE activity (ECAi) and low ACE activity (ECAb). Heredity phenotypes were proven, which led to the establishment of a new strain of animals: Wistar/INFAR/ECAa and Wistar/INFAR/ECAb. However, The blood pressure of the animals, were not different between the phenotypes, a puzzling fact taking into account the participation of the renin-angiotensin-aldosterone system (RAAS) and the kallikrein-kinin system (KKS) in maintaining blood pressure. From these data, this study aims to analyze the effect of bradykinin and other kinins in the vascular reactivity of these rats with different phenotypes of ACE using agonists and antagonists of the parasympathetic nervous system (SNP), RAAS and KKS. Therefore, we evaluated the participation of these systems in vitro in thoracic aorta of male rats ECAa and ECAb. In the study of acetylcholine in the presence and absence of atropine it was not possible to detect significant differences between phenotypes and in the presence of atropine, showed a vasodilator concentration-dependent blocked response. In the analysis of the KKS using bradykinin (BK), we observed a similar hypotensive effect between phenotypes and when preincubated the B2 receptor antagonist of bradykinin (HOE-140), we observed a significant reduction of the vasodilatory effect (Emax) concentration-dependent, indicating thus the response of bradykinin might be mediated mainly via the B2 receptor. Also about bradykinin, we found that its action takes place predominantly via nitric oxide (NO) because when pre-incubated the NOS inhibitor (L-NAME), a significant reduction of vasorelaxant response was observed, but again, with no significant differences between phenotypes. It was also studied the action of des-Arg9-BK, an active BK-metabolite, which was possible to observe a response very similar to BK, although with a lower Emax, thus suggesting a lower affinity and activation of the B2 receptor, which is expressed constitutively. In the study of phosphorylated kinin we observed a decreased response of the phophorylated bradykinin compared to non-phosphorylated form, indicating a direct effect of the phosphate group (-PO3H2) in the interaction and activation of kinin receptors. Finally, we determined the vasodilator response of Ang (1-7), as well as its influence on bradykinin, which potentiated the vasodilatory action of BK, but with no differences between the phenotypes. In conclusion, the findings of this study serve to highlight that although these animals have different phenotypes (ECAa, ECAb), they do not have distinct responses to these vasodilators, ie the enzymatic phenotypes of ACE does not seem to influence the final responses of the vasoactive substances studied, due possibly exist compensatory mechanisms by alternative pathways different of the RAAS and KKS.
- ItemAcesso aberto (Open Access)Pediatric dyslipidemia is associated with increased urinary ACE activity, blood pressure values, and carotidal-femoral pulse wave velocity(Spring Nature, 2023-03-24) Cruz, Nayara Azinheira Nobrega [UNIFESP]; Oliveira, Lilian Caroline Gonçalves [UNIFESP]; Fernandes, Fernanda Barrinha; Zaniqueli, Divanei dos Anjos; Oliosa, Polyana Romano; Mill, José Geraldo; Casarini, Dulce Elena [UNIFSP]; https://lattes.cnpq.br/8161092089656847This study aimed to evaluate the enzymatic activity of the angiotensin-converting enzyme (ACE) in children and adolescents to investigate their relationship with dyslipidemia and other cardiometabolic alterations. Anthropometric measurements, blood pressure (BP), and fasting lipid concentrations were taken from 360 subjects. Categorization was done according to the levels of each lipoprotein (total cholesterol, triglycerides (TG), LDL-C, HDL-C, and non-HDL-C) into three groups: normolipidemic (NL), borderline (BL), and dyslipidemic (DL). Enzymatic activity in urine was measured using the substrates Z-FHL-OH and hippuryl-HL-OH (h-HL-OH) and the ACE activity ratio (Z-FHL-OH/h-HL-OH) was calculated. Dyslipidemic levels of HDL-C, TG, and LDL-C were observed in 23%, 9%, and 3% of the participants, respectively, and were more frequent in obese children (Chi-square, p < 0.001). ACE activity ratio was augmented in BL(HDL-C) when compared to NL(HDL-C) (5.06 vs. 2.39, p < 0.01), in DL(LDL-C) in comparison to BL(LDL-C) and NL(LDL-C) (8.7 vs. 1.8 vs. 3.0, p < 0.01), and in DL(non-HDL-C) than in BL(non-HDL-C) and in NL(non-HDL-C) (6.3 vs. 2.1 vs. 2.9, p = 0.02). The groups with impaired HDL-C and TG levels presented an increased diastolic BP percentile, and a higher systolic BP percentile was observed in BL(TG) and DL(TG). The carotidal-femoral pulse wave velocity (cfPWV) was higher in the groups with DL levels of TG and LDL-C than in NL groups. Hypertriglyceridemia was associated with higher cfPWV. No direct impact of the ACE activity on BP values was observed in this cohort, however, there was an association between hyperlipidemia and ACE upregulation which can trigger mechanisms driving to early onset of hypertension and cardiovascular disease. Graphical abstract exemplifying the cohort, categorization of subjects into the groups NL normolipidemic, BL borderline, DL dyslipidemic, methods, and main findings. Pediatric dyslipidemia was consistent with dyslipidemia secondary to obesity (DSO), associated with higher urinary angiotensin-converting enzyme (ACE) activity ratio, BP blood pressure values, and carotidal-femoral pulse wave velocity (cfPWV).
- ItemSomente MetadadadosPurification and characterization of angiotensin I-converting enzymes from mesangial cells in culture(Lippincott Williams & Wilkins, 1998-12-01) Andrade, Maria C.C.[UNIFESP]; Quinto, Beata M.R. [UNIFESP]; Carmona, Adriana K. [UNIFESP]; Ribas, Otoniel S. [UNIFESP]; Boim, Miriam A. [UNIFESP]; Schor, Nestor [UNIFESP]; Casarini, Dulce E. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Objective Previous analysis of the angiotensin I-converting enzyme (ACE) gene in this laboratory showed that primary mesangial cells in culture are able to express ACE mRNA. Moreover, ACE is produced as an ectoenzyme and as a secreted form of the enzyme, indicating a potential effect of local angiotensin II production on glomerular microcirculation. the aim of this study was to purify and characterize the secreted end intracellular ACE forms from mesangial cells in culture.Methods and results Medium from Wister rats mesangial cells was collected (third passage), incubated for 20 h with RPMI without fetal bovine serum and concentrated 29 times in an Amicon concentrator. the concentrated medium was submitted to gel filtration on an AcA-34 column and two peaks (ACE(1), mol. wt 130 000 and ACE(2), 60 000) with ACE on activity Hippuryl-His-Leu and Z-Phe-His-Leu were separated. the mesangial cells were collected and ACE enzyme was extracted using Triton X-114, followed by centrifugation and concentration. the supernatant was submitted to the same chromatography as described above and two peaks with ACE activity (ACE(Int1), mol. wt 130 000 and ACE(Int2), 68 000) were separated. the purified ACE were inhibited by enalaprilat and captopril, two potent competitive inhibitors of ACE and by EDTA, using Hippuryl-His-Leu as a substrate. the K-m values were 2 mM for ACE(1) and ACE(2) and 3 mM for ACE(Int1) end ACE(Int2). the enzymes ACE(1) and ACE(2) presented an optimum pH of 8.0 and ACE(Int1) and ACE(Int2) an optimum pH of 7.5.Conclusion the activities of full-length wild-type and N-domain ACE were characterized by the ratio of the hydrolysis of Z-Phe-His-Leu/Hippuryl-His-Leu, which was 1 and 4, respectively. the ratios found for ACE(1), ACE(2), ACE(Int1) and ACE(Int2) in the present study were similar to those described above, suggesting that mesangial cells, besides showing the presence of intracellular ACE, are able to secret both full-length wild-type ACE and N-domain ACE. Thus, they may potentially have an effect, not only on bradykinin and angiotensin I (ACE wild-type), but also on substance P, luteinizing hormone-releasing hormone and Met-enkephalin to interfere with glomerular haemodynamics and with the renal microcirculation. I Hypertens 1998, 16:2063-2074 (C) 1998 Lippincott Williams & Wilkins.