Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-06-02T21:45:30Z No. of bitstreams: 1 VictorHugoRezendeDuarte_DISSERT.pdf: 944081 bytes, checksum: b102ccdae8dc58e29f3c26819c75b9c6 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-06-07T21:07:26Z (GMT) No. of bitstreams: 1 VictorHugoRezendeDuarte_DISSERT.pdf: 944081 bytes, checksum: b102ccdae8dc58e29f3c26819c75b9c6 (MD5) / Made available in DSpace on 2017-06-07T21:07:26Z (GMT). No. of bitstreams: 1 VictorHugoRezendeDuarte_DISSERT.pdf: 944081 bytes, checksum: b102ccdae8dc58e29f3c26819c75b9c6 (MD5) Previous issue date: 2017-04-26 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / As prote?nas da fam?lia triggering receptor expressed on myeloid cells (TREM) s?o associados com o risco e progress?o da aterosclerose. Em resultados pr?vios observamos que a alta express?o do TREML4est? relacionada com fase inicial da S?ndrome Coronariana Aguda (SCA).Neste estudo, investigamos a rela??o dos polimorfismos e a express?o do RNAm do TREML4 em leuc?citos de pacientes estratificados de acordo com a extens?o das les?es das atr?rias coron?rias. Foram inclu?dos pacientes com doen?a arterial coronariana (DAC) (n=151), com idades entre 30 e 74 anos, submetidos ? angiografia coron?ria eletiva. A extens?o da les?o coronariana foi avaliada atrav?s do ?ndice de Friesinger. Os polimorfismosrs2803495 (A> G), rs2803496 (T> C) e aexpress?o do RNAm do TREML4 em leuc?citos foram analisadas por qRT-PCR. A express?o de TREML4 foi maior em pacientes com les?es coronarianas graves em rela??o aos sem les?o, baixas e intermedi?rias, (p <0.05). Indiv?duos portadores do alelo G do rs2803495 (gen?tipos AG / GG) e do alelo C do rs2803496(gen?tipos TC / CC) apresentaram uma express?o de RNAm de TREML4 positiva (Alelo G: OR = 2.4, 95% CI 1.0-5.7, p < 0.05; e Alelo C: OR = 7.8, 95% CI = 2.9-20.9, p < 0.01, respectivamente).Entretanto, os polimorfismos do TREML4 n?o foram associados com as extens?es das les?es coron?rias. Em conclus?o, a express?o aumentada de mRNA de TREML4 nos leuc?citos ? influenciada por polimorfismos e est? associada a les?es mais graves das art?rias coron?rias, sugerindo seu papel como potencial biomarcador para investigar a extens?o da les?o coronariana em pacientes com DAC. / The members of the triggering receptor expressed on myeloid cells (TREM) family are associated with the risk and progression of atherosclerosis. We previously reported the upregulation of TREML4 in the early phase of theacute coronary syndrome. Here, we investigated the relationship of TREML4 polymorphisms and mRNA expression in blood leukocytes of patients stratificate accordingto the extension of coronary artery lesion. Patients with coronary artery disease (CAD) (n = 151), aged 30 to 74 years and undergoing elective coronary angiography,were selected. The extension of coronary lesion was assessed by the Friesinger index.TREML4 rs2803495 (A>G) and rs2803496 (T>C) variants andleukocyte mRNA expression were analyzed by qRT-PCR. TREML4 expression was higher in patients with major coronary artery lesions compared to subjects without or with low and intermediate lesions, (p < 0.05). Subjects carrying rs2803495 G allele (AG/GG genotypes) and rs2803496 C allele (TC/CC genotypes) were more prone to have positive TREML4 mRNA expression (Allele G: OR = 2.4, 95% CI 1.0-5.7, p < 0.05; allele C: OR = 7.8, and 95% CI = 2.9-20.9, p < 0.01, respectively).However, TREML4 polymorphisms were not associated with the extent of coronary lesion.In conclusion, increased TREML4 mRNA expression in blood leukocytes is influenced by gene polymorphisms and it is associated with more severe coronary artery lesions, suggesting its role as potential biomarker to investigate the extent of coronary lesion in CAD patients.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-03-21T18:51:09Z No. of bitstreams: 1 MychelleKytchiaRodriguesNunesDuarte_DISSERT.pdf: 2556724 bytes, checksum: 7d5fee1d4fe61eba6aa3c5ddd4fa6747 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-03-28T00:32:58Z (GMT) No. of bitstreams: 1 MychelleKytchiaRodriguesNunesDuarte_DISSERT.pdf: 2556724 bytes, checksum: 7d5fee1d4fe61eba6aa3c5ddd4fa6747 (MD5) / Made available in DSpace on 2017-03-28T00:32:58Z (GMT). No. of bitstreams: 1 MychelleKytchiaRodriguesNunesDuarte_DISSERT.pdf: 2556724 bytes, checksum: 7d5fee1d4fe61eba6aa3c5ddd4fa6747 (MD5) Previous issue date: 2016-12-06 / A doen?a arterial coronarina ? uma das principais causa de ?bitos em todo o mundo e pode ser desencadeada por altera??es no perfil s?rico de ?cidos graxos, nos padr?es de express?o g?nica, no consumo alimentar e diet?tico e por desequil?brios antropom?tricos e/ou de composi??o corporal. O diagn?stico precoce desta doen?a ? um desafio na medicina translacional, visto que os m?todos utilizados s?o onerosos e/ou invasivos. O trabalho ent?o teve como objetivo identificar biomarcadores para o diagn?stico precoce da aterosclerose por meio do perfil serico de ?cidos graxos, express?o do RNAm da enoil-coA-hidratase (ECDHC3) e de fatores nutricionais em pacientes sem les?es e com diferentes extens?es da les?o ateroscler?tica. Realizou-se um estudo observacional, com a amostragem coletada por conveni?ncia, formada por pacientes que iriam realizar pela primeira vez a cinecoronariogradia no setor de Hemodin?mica do Hospital Universit?rio Onofre Lopes. Na primeira casu?stica participam 59 pacientes (n1, 2011-2013) e na segunda 41 (n2, 2014-2015), ambos com idade entre 30-74 anos. Determinou-se a extens?o das les?es por meio do ?ndice de Friesinger, o perfil bioqu?mico (glic?mico,lipid?mico) por espectrometria semiautomatizado; concentra??o s?rica de ?cidos graxos pela cromatografia gasosa; express?o do RNAm do ECHDC3 pela rea??o de cadeia de prolimerase (PCR) em tempo real; consumo alimentar e diet?tico por dois recordat?rios de 24h, par?metros antropom?tricos e composi??o corporal pela balan?a com bioimped?ncia el?trica, fita m?trica e estadiometro. Os pacientes foram classificados em grupos: sem les?o (n1=18/n2 =8), poucas les?es (n1=17/n2=6), intermedi?rias (n1=17/n2=15) e graves (n1=7/n2=12). Na primeira casu?stica foi encontrado elevadas concentra??es s?ricas de ?cido ol?ico e de ?cidos graxos monoinsaturados nos pacientes com poucas les?es e intermedi?rias, quando comparado com pacientes sem les?o (p<0,05). A express?o do ECHDC3 foi 1,2 vezes mais alta em pacientes com poucas les?es que em pacientes sem les?o (p=0,023), e 1,8 vezes mais baixa em pacientes com les?o grave que em pacientes sem les?o (p=0,020). Na segunda casu?stica, a express?o do ECHDC3 foi 1,93 mais alta em pacientes com les?o intermedi?ria do que com poucas les?es (p = 0.011) e 1,91 vezes mais alta em pacientes com les?o grave que em poucas les?es (p = 0.013). A an?lise de Spearman mostrou uma correla??o entre os grupos de Friesinger com a express?o do ECHDC3 (r = 0.327, p =0.037) , e deste com o percentual de gordura visceral (r = 0.416, p =0.009). O ?ndice de Friesinger tamb?m mostrou uma correla??o com o consumo de carboidrato (r = 0.754, p = 0.002), vitamina B1 (r = 0.507, p = 0.001), vitamina B2 (r = 0.388, p = 0.012), folato (r = 0.599, p = 0.000) e magn?sio (r = 0.528, p = 0.003). Verificou-se que o aumento de ?cido ol?ico s?rico, da express?o do ECHDC3 e da gordura visceral podem contribuir para a progress?o da aterosclerose, uma vez que estes podem favorecer a ? ? oxida??o, rea??o que favorece a forma??o de esp?cies reativas de oxig?nio, desencadeando inflama??o, um dos principais gatilhos para a aterosclerose. Tamb?m foi visto que o consumo de carboidratos e alguns micronutrientes podem favorecer a progress?o da aterosclerose, j? que o aumento da ingest?o destes nutrientes pode propiciar a defici?ncia na absor??o ou estresse oxidativo, que implica diretamente na etiologia desta doen?a. / Coronary arterial disease is a at leading cause of death worldwide and can be triggered by alterations in the serum profile of fatty acids, by patterns of gene expression, changes in dietary intake, and alteration anthropometric. The early diagnosis of this pathophysiology is a challenge in translational medicine, since the methods used are expensive and / or invasive. The aim in the study was to identify biomarkers for the early diagnosis of atherosclerosis through the relationship of serum fatty acid profile, enoyl-coA hydratase (ECDHC3) mRNA expression and nutritional factors in patients without lesions and with different extensions of the atherosclerotic lesion. The study was observational, with the sample collected for convenience in two casuistry in the Hemodynamics sector of the Onofre Lopes University Hospital (HUOL). In the first series, 59 patients partipated (n1, 2011-2013) and in the second 41 individuals ( n2, 2014-2015), both aged 30-74 years and who were undergoing coronariography for the first time. The extent of atherosclerotic lesions was determined by Friesinger index, the biochemical profile by semi-automated spectrometry; the concentration of fatty acids by gas chromatography; gene expression of ECHDC3 mRNA by real-time PCR; food consumption and dietary intake for two 24-hour dietary intake recalls, anthropometric parameters and corporal composition by the electric bioimpedance, measuring tape and stadiometer scale.Patients were classified into groups: no lesion (n1 = 18 / n2 = 8), low lesions (n1 = 17 / n2 = 6), intermediate lesions (n1 = 17 / n2 = 15) and major lesion (n1= 7 / n2 = 12). In n1 was observed high serum concentrations of oleic acid and monounsaturated fatty acids in patients with low lesions and intermediate when compared to patients without lesions (p <0.05). ECHDC3 expression was 1.2 fold-higher in patients with low lesions than in patients without lesions (p = 0.023), and 1.8 fold- lower in patients with major lesions than in patients without lesions (p = 0.020). In the second casuistry, the expression of ECHDC3 was 1.93 fold-higher in patients with intermediate lesions than in low lesions (p = 0.011) and 1.91 fold-higher in patients with severe lesions than in low lesions (p = 0.013). Spearman's analysis showed a positive correlation showed a between ECHDC3 mRNA expression and Friesinger index (r = 0.327, p = 0.037), between the gene and visceral fat (r = 0.416, p = 0.009). The Friesinger index also showed a correlation with the consumption of carbohydrate (r = 0.754, p = 0.002), vitamin B1 (r = 0.507, p = 0.001), vitamin B2 (r = 0.388, p = 0.012), folate (r = 0.599, p = 0.000), magnesium (r = 0.528, p = 0.003). It was verified that oleic acid, ECHDC3 expression, percentage of visceral fat could favors ?-oxidation, trigger for inflammation and CVD; while the greater consumption of carbohydrate and some micronutrients, also could be associated with the CVD development, since the excess or decreased absorption can favors the oxidative stress, that favors the atherosclerosis.