Avaliação da expressão proteica e de elementos em plasma sanguíneo após o uso de estatinas em pacientes infartados
Data
2022-10-04
Autores
Araujo, Isabela Carvalho Lobo de 
Orientadores
Lopes, Aline Soriano
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Estudos a nível molecular envolvendo pacientes que sofreram infarto agudo do miocárdio fornecem uma nova visão sobre o conhecimento da expressão clínica e patológica da doença. Atualmente, avanços tecnológicos nas plataformas conhecidas com a terminologia “ômicas” permitem a avaliação de mudanças sistemáticas em diversos sistemas biológicos e tem sido aplicada extensivamente a doenças cardiovasculares. O sangue está em contato direto e constante com o sistema cardíaco, fazendo do plasma o fluido mais adequado para o estudo dos componentes advindos de uma oclusão coronária, que é o caso do infarto. Além das proteínas, o plasma possui diversas outras moléculas biológicas interessantes, tais como macro e micronutrientes elementares. A avaliação do perfil proteico por meio da proteômica tem auxiliado na compreensão da evolução de doenças e estratégias terapêuticas. Ainda, sabe-se que há interação entre diversos elementos químicos com proteínas e essa interação pode ser modificada devido a algum distúrbio biológico como uma doença ou uso de fármacos. Logo, o estudo dos íons elementares em conjunto com as proteínas pode aumentar as informações sobre as doenças cardiovasculares, além de ampliar o conhecimento sobre a ação de fármacos no organismo. Dentro deste cenário, o objetivo desse estudo foi avaliar a expressão proteica diferencial em pacientes infartados e tratados com duas estatinas diferentes, bem como explorar possíveis alterações de elementos essenciais na evolução desses pacientes, e corroborar os resultados oriundos dos dois estudos. Um total de 199 proteínas foram identificadas; entre as quais, 11 proteínas foram expressas de forma significativa entre os grupos de pacientes estudados. Algumas proteínas estão relacionadas a processos de agregação plaquetária, tais como o fibrinogênio e a hemoglobina; enquanto outras exercem a função de associação de íons cálcio, tais como a Proteína C reativa, subcomponente do Complemento C1s e Paraoxonase / arilesterase 1 sérica. Pela análise de agrupamento hierárquico observou-se que o perfil proteico é mais diferentemente expresso com relação ao tempo de administração da droga do que o tipo de estatina usada no tratamento do infarto. O mesmo comportamento foi observado na análise de PCSK9, em que maiores concentrações foram encontradas em decorrência do tempo de tratamento. Entre os íons elementares analisados, apenas o cobre apresentou variação significativa entre as visitas. A redução nos níveis de cobre no plasma, pode estar relacionada com o aumento de expressão da proteína Paraoxonase 1 sérica.
Molecular level studies involving patients who have suffered acute myocardial infarction provide new insights into the knowledge of the clinical and pathological expression of the disease. Nowadays, technological advances in “omics” platforms allow the evaluation of systematic changes in several biological systems and have been extremely applied to cardiovascular diseases. Blood is in direct and constant contact with the cardiac system, turning plasma into the most suitable fluid for the study of components originating from a coronary occlusion, such as infarction. In addition to proteins, plasma has many other interesting biological molecules, such as elemental macro and micronutrients. Evaluations of the protein profile through proteomics has helped to understand the evolution of diseases and therapeutic strategies. Furthermore, it is known that there is an interaction between several chemical elements and proteins, and this interaction can be modified due to some biological disorder such as a disease or drug administration. Therefore, the study of elemental ions associated with proteins can increase information about cardiovascular diseases, in addition to expanding knowledge about the action of drugs in organisms. In this scenario, this study aimed to evaluate differential protein expression in infarcted patients treated with two different statins, as well as to explore possible variations in essential elements in the evolution of these patients, and to corroborate the results from both studies. A total of 199 proteins were identified; among which, 11 proteins were significantly expressed among the group of patients studied. Some proteins are related to platelet aggregation processes, such as fibrinogen and hemoglobin; while others perform the function of association of calcium ions, such as C reactive protein, complement C1s subcomponent and serum paraoxonase/arylesterase 1. By hierarchical cluster analysis, we observed that the protein profile is more differently expressed related to the time of drug administration than the type of statin used in the treatment of infarction. A similar behavior was observed in the analysis of PCSK9, in which higher concentrations were found as a result of the treatment time. Among the elemental ions analyzed, only copper showed significant variation between visits. The reduction in plasma copper levels may be related to the increased expression of the protein serum paraoxonase 1.
Molecular level studies involving patients who have suffered acute myocardial infarction provide new insights into the knowledge of the clinical and pathological expression of the disease. Nowadays, technological advances in “omics” platforms allow the evaluation of systematic changes in several biological systems and have been extremely applied to cardiovascular diseases. Blood is in direct and constant contact with the cardiac system, turning plasma into the most suitable fluid for the study of components originating from a coronary occlusion, such as infarction. In addition to proteins, plasma has many other interesting biological molecules, such as elemental macro and micronutrients. Evaluations of the protein profile through proteomics has helped to understand the evolution of diseases and therapeutic strategies. Furthermore, it is known that there is an interaction between several chemical elements and proteins, and this interaction can be modified due to some biological disorder such as a disease or drug administration. Therefore, the study of elemental ions associated with proteins can increase information about cardiovascular diseases, in addition to expanding knowledge about the action of drugs in organisms. In this scenario, this study aimed to evaluate differential protein expression in infarcted patients treated with two different statins, as well as to explore possible variations in essential elements in the evolution of these patients, and to corroborate the results from both studies. A total of 199 proteins were identified; among which, 11 proteins were significantly expressed among the group of patients studied. Some proteins are related to platelet aggregation processes, such as fibrinogen and hemoglobin; while others perform the function of association of calcium ions, such as C reactive protein, complement C1s subcomponent and serum paraoxonase/arylesterase 1. By hierarchical cluster analysis, we observed that the protein profile is more differently expressed related to the time of drug administration than the type of statin used in the treatment of infarction. A similar behavior was observed in the analysis of PCSK9, in which higher concentrations were found as a result of the treatment time. Among the elemental ions analyzed, only copper showed significant variation between visits. The reduction in plasma copper levels may be related to the increased expression of the protein serum paraoxonase 1.