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Master's Dissertation
DOI
10.11606/D.9.2017.tde-24052017-161009
Document
Author
Full name
Magda Elizabeth Graciano Saldarriaga
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2017
Supervisor
Committee
Hirata, Mario Hiroyuki (President)
Bertolami, Marcelo Chiara
Rodrigues, Alice Cristina
Sampaio, Marcelo Ferraz
Title in Portuguese
Pesquisa de miRNAs circulantes, potenciais biomarcadores de aterosclerose subclínica em indivíduos euglicêmicos e pré-diabéticos
Keywords in Portuguese
Aterosclerose subclínica
Biomarcadores
Diabete Melito tipo 2
Doença arterial coronariana
MiRNAs
Pré-diabete
Abstract in Portuguese
As doenças cardiovasculares e o diabete melito fazem parte das DCNT prioritárias da OMS, devido às altas taxas de morbimortalidade e incapacidade que geram a cada ano. Estima-se que no mundo existam 387 milhões de diabéticos e outros 316 milhões de pessoas com características de risco, como pré-diabete. Cerca de 60% dos pacientes com DM2 desenvolvem doença cardiovascular, a qual inicia de forma concomitante aos distúrbios do metabolismo da glicose, podendo existir mecanismos fisiopatológicos comuns entre as doenças. Metade dos eventos coronarianos, inclusive a morte súbita, ocorrem em indivíduos assintomáticos, evidenciando a necessidade de novos marcadores precoces, já que em muitos deles a morte é a primeira manifestação. Recentemente, tem sido sugerido que os miRNAs envolvidos na regulação da expressão gênica podem ser caracterizados como biomarcadores em diversas doenças. Nosso objetivo é identificar alterações no perfil de miRNAs circulantes em indivíduos euglicêmicos e pré-diabéticos com e sem aterosclerose subclínica, utilizando a tecnologia de qPCR Arrays, com a finalidade de identificar candidatos a biomarcadores moleculares dessa condição. Encontrou-se que a aterosclerose subclínica esteve associada com o envelhecimento, a menopausa, etnia branca, dislipidemia, resistência à insulina, o aumento da adiposidade, leptina e do TNF-α. O aumento do miR98-5p e a diminuição dos miRNAs miR-212-3p, miR-145-5p, miR-93-5p, miR15a-5p, miR-19a-3p, miR32-5p levaram a ativação da via de sinalização da aterosclerose. Os resultados sugerem que a inflamação foi o principal mecanismo associado com o desenvolvimento de aterosclerose subclínica neste estudo.
Title in English
Search of circulating miRNAs, potential biomarkers of subclinical atherosclerosis in euglycemic and pre-diabetic subjects
Keywords in English
Biomarkers
Coronary heart disease
MiRNAs
Prediabetes
Subclinical atherosclerosis
Type 2 diabetes mellitus
Abstract in English
Cardiovascular Disease and Diabetes Mellitus are relevant NCDs for the WHO. It´s estimated that, worldwide, there are 387 millions of diabetics and 316 millions of people with risk characteristics like prediabetes. About 60% of patients with T2DM develops cardiovascular disease, which starts at the same time as disorders of glucose metabolism, there may be common pathophysiological mechanisms among diseases. Half of coronary events, including sudden death, occurs in asymptomatic individuals. This fact, highlights the need for new early markers of the disease, especially in asymptomatic patients, since in many of them, death is the first manifestation. It has been recently suggested that miRNAs involved in pos-transcriptional regulation of gene expression, could be characterized as biomarkers of diseases. Our goal is to identify changes in the profile of circulating microRNAs in euglycemic and prediabetic patients with or without subclinical atherosclerosis, by quantitative Polymerase Chain Reaction array (qPCR Array) in order to find molecular biomarkers of this condition. We found that subclinical atherosclerosis was associated with aging, menopause, white ethnicity, dyslipidemia, insulin resistance, increased adiposity, leptin and TNF-α. The up-regulation of miR98-5p and the down-regulation miR-212-3p, miR-145-5p, miR-93-5p, miR15a-5p, miR-19a-3p, miR32-5p led to activation of the signaling pathway of atherosclerosis. The results suggest that inflammation was the main mechanism associated with the development of subclinical atherosclerosis in this study.
 
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Publishing Date
2017-05-30
 
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