Polimorfismos gen?tico e proteico da enzima conversora de angiotensina na s?ndrome de pr?-ecl?mpsia

• Main Author: Krauspenhar, Bruna
• Other Authors: Costa, Bartira Erc?lia Pinheiro da
• Format: Others
• Language: Portuguese
• Published: Pontif?cia Universidade Cat?lica do Rio Grande do Sul 2015
• Subjects: MEDICINA; PR?-ECL?MPSIA; PEPT?DIOS; HIPERTENS?O ARTERIAL; CIENCIAS DA SAUDE::MEDICINA
• Online Access: http://tede2.pucrs.br/tede2/handle/tede/6064

Submitted by Setor de Tratamento da Informa??o - BC/PUCRS ([e-mail]) on 2015-05-28T11:40:36Z No. of bitstreams: 1 469525 - Texto Completo.pdf: 2925199 bytes, checksum: d0ce1f2f0c3cdc1d309d3f09e9a7d239 (MD5) === Made available in DSpace on 2015-05-28T11:40:36Z (GMT). No. of bitstreams: 1 469525 - Texto Completo.pdf: 2925199 bytes, checksum: d0ce1f2f0c3cdc1d309d3f09e9a7d239 (MD5) Previous issue date: 2015-03-02 === Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES === Introduction: Preeclampsia is a disease characterized as high maternal and fetal morbidity and mortality, diagnosed only after 20th gestational week, its etiology is not completely understood and healing is placental removal. It has been looking for biomarkers that allow early diagnosis for a better outcome of the disease. The 90 kDa isoform of Angiotensin Converting Enzyme (ACE), proposed as a new biomarker for hypertension, has not been studied in the preeclampsia syndrome so far. Objective: To evaluate the gene and protein expression, as well as enzymatic activity of ACE in pregnancy induced hypertension. Material and methods: It were included 69 normotensive and preeclampsia syndrome pregnant women at S?o Lucas Hospital/PUCRS, Porto Alegre/ RS- Brazil. Blood sample was collected to perform ACE genetic polymorphism, and three urine samples (during pregnancy, after delivery and at least 3 months after delivery) were taken to perform ACE protein polymorphism and enzymatic activity. This study was conducted through a partnership between Nephrology Service from PUCRS and Kidneys and Hormones from UNIFESP Laboratories research. Results: Scientific paper was published in Medical Hypotheses journal, entitled ?Angiotensin Converting Enzyme 90 kDa isoform: Biomarker for diagnosis of preeclampsia?? that described the hypotheses of this research. Comparing the participants clinical data among the groups (Normal pregnant, pure preeclampsia, superimposed preeclampsia), statistical significancy was observed between obstetric gestational age, blood pressure, newborn weight (p< 0.001) and placental weight (p= 0.030). Hypertension familial history compared with ACE genotypes (p= 0.017) suggests allele I involvement. Enzymatic activity ZPhe and Hhl ratio was different during the gestational period (p< 0.025), and also in relation to the ACE genotypes (p< 0.001). ZPhe and HhL isolated enzymatic activity also, in relation to the ACE genotypes, was not statistically different (p = 0.83 e p = 0.16, respectively). The protein polymorphism was not performed due to some technique problems, but this activity will be finished as soon as possible. Conclusion: It seems that allele I is associated with the hypertension familial history, and the genotypes that have this allele (ID, II) are predominantly present in pregnant women with preeclampsia. Enzymatic activity of Zphe/Hhl shows different behavior during the gestational period, and it also change according to genotypes classification. The data suggest that the mechanism involved in essential hypertension can be different from those involved in transient and spontaneous hypertension triggered pregnancy induced hypertension. === Introdu??o: Pr?-ecl?mpsia ? uma doen?a de alta morbimortalidade materna e fetal, diagnosticada somente ap?s a 20? semana gestacional, de etiologia n?o totalmente esclarecida e a cura consiste na retirada da placenta. Segue-se na busca de biomarcadores que possibilitem um diagn?stico precoce para um melhor desfecho da doen?a. A isoforma 90 kDa da Enzima Conversora de Angiotensina (ECA), proposta como novo marcador de hipertens?o, ainda n?o foi estudada na s?ndrome de pr?-ecl?mpsia. Objetivos: Avaliar a express?o gen?tica, proteica e enzim?tica da ECA na Doen?a Hipertensiva Gestacional. Materiais e m?todos: Foram inclu?das 69 gestantes normotensas e com S?ndrome de Pr?-ecl?mpsia (Pr?-ecl?mpsia Pura ou Sobreposta) no Hospital S?o Lucas da PUCRS, Porto Alegre/ RS- Brasil. Foram coletadas uma amostra de sangue para realizar o polimorfismo gen?tico da ECA e 3 amostras de urina (durante a gesta??o, ap?s o parto e pelo 3 meses ap?s o parto) para realizar a an?lise do polimorfismo proteico e a atividade enzim?tica da ECA. Este estudo teve parceria entre os laborat?rios de pesquisa de Nefrologia da PUCRS e Rins e Horm?nios da UNIFESP. Resultados: Foi publicado um artigo cient?fico na revista Medical Hypotheses, intitulado em Angiotensin Converting Enzyme 90 kDa isoform: Biomarker for diagnosis of preeclampsia?, descrevendo a hip?tese desta pesquisa. Comparando os dados cl?nicos das participantes entre os grupos analisados (Gestante normal, Pr?- ecl?mpsia Pura e Pr?- eclampsia Sobreposta), houve signific?ncia estat?stica entre idade gestacional obst?trica, n?veis press?ricos, peso do rec?m-nascido (p<0,001) e peso da placenta (p= 0,030). A hist?ria familiar de hipertens?o comparada com os gen?tipos da ECA (p= 0,017) sugere envolvimento do alelo I. A raz?o da atividade enzim?tica de Zphe e Hhl foi diferente durante o per?odo gestacional (p<0,025) e tamb?m em rela??o aos gen?tipos da ECA (p<0,001). Enquanto que a atividade enzim?tica isolada de Zphe e Hhl em rela??o aos gen?tipos da ECA n?o foi significativa (p = 0,83 e p = 0,16, respectivamente). A an?lise do polimorfismo proteico n?o foi realizada devido a problemas na execu??o da t?cnica, mas essa atividade ser? conclu?da assim que poss?vel. Conclus?o: O alelo I parece estar associado com a hist?ria familiar de hipertens?o e os gen?tipos que possuem esse alelo (ID, II) est?o predominantemente mais presentes nas gestantes que apresentam pr?-ecl?mpsia. A atividade enzim?tica de ZPhe/Hhl apresenta comportamento diferente durante o per?odo gestacional e tamb?m se altera conforme a classifica??o genot?pica da gestante. Os dados sugerem que os mecanismos envolvidos na hipertens?o essencial possam ser diferentes dos envolvidos na hipertens?o transit?ria e espont?nea desencadeada nas Doen?as Hipertensivas Gestacionais.