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Heparanase e dislipidemia
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Introdução: A heparanase é uma enzima que degrada as cadeias de sulfato de heparano, cadeias que fazem parte dos proteoglicanos de sulfato de heparano, presentes na matriz extracelular. Esta complexa enzima parece ter papeis enzimáticos e não enzimáticos importantes, quer extra quer intracelulares. De entre as várias ações da heparanase, destacam-se as relacionadas com o metabolismo dos lípidos. A dislipidemia é uma patologia com uma crescente prevalência na população portuguesa. Sendo a heparanase uma enzima de efeitos pleiotrópicos, o seu potencial como alvo terapêutico, poderá vir a ser uma opção no controlo da dislipidemia no âmbito de prevenção primária ou secundária.
Objetivos: O objetivo é reunir, organizar e sumarizar a informação existente sobre as diferentes descobertas da heparanase, nomeadamente no âmbito do metabolismo dos lipídios, de forma a perceber o potencial desta enzima como alvo terapêutico na dislipidemia.
Metodologia: Realizou-se uma pesquisa bibliográfica na base de dados Medline com auxílio do motor de busca PubMed, assim como na base de dados da Cochrane e na Web of Science Core Collection com as expressões heparanase e colesterol, refinado com inibidores da heparanase. Foram selecionados os artigos escritos entre 1990-2022, redigidos em inglês e português. Foram consultadas ainda, diretivas da European Society of Cardiology e estudos do Instituto Ricardo Jorge assim como manuais de Medicina Clínica nomeadamente, o livro Manual Oxford de Medicina Clínica.
Conclusão: Este trabalho permite concluir que a heparanase está associada ao metabolismo dos lípidos e dislipidemia e que, a inibição da sua atividade, pode reduzir a transdução de genes associados à aterosclerose e, a nível extracelular, melhorar a disponibilidade dos recetores hepáticos associados à depuração de resíduos lipídicos, facilitado pela apolipoproteína E. Deste trabalho evidencia-se a carência de estudos como ensaios clínicos, que visem a ação dos inibidores da heparanase no tratamento das perturbações do metabolismo lipídico, podendo constituir estes inibidores, uma mais-valia na abordagem da dislipidemia e prevenção das suas consequências.
Introduction: Heparanase is an enzyme capable of degrading heparano-sulfate chains, these chains are an integral part of heparano-sulfate proteoglycans which are expressed in extracellular matrix. This complex enzyme seems to have enzymatic and non-enzymatic roles whether it be extra or intracellularly. Amongst the different actions of heparanase, it demonstrates interactions at the level of lipid metabolism. Dyslipidemia has a growing prevalence in the Portuguese population. Being a pleiotropic enzyme, heparanase displays a potencial therapeutic target, that might turn into an add-on option against dyslipidemia in the midst of primary or secondary prevention. Objectives: The main objective is gathering, organising and summarization information regarding various discoveries about heparanase, regarding lipid metabolism so as to understand the potential of the enzyme as a therapeutic target in dyslipidemia. Methodology: Literature review was made through a search on Medlines data base using the research engine PubMed, as well as Cochrane and Web of Science Core Collection data basis with the expressions heparinase and cholesterol refined with heparinase inhibitors. From these results, articles written from 1990 to 2021, redacted in English and Portuguese were selected. Complementary to these sources, guidelines of European Society of Cardiology, a Portuguese study from Instituto Ricardo Jorge and manuals of Clinical Medicine namely, Manual Oxford of Clinical Medicine were consulted in the makings of this work. Conclusion: This work concludes that heparanase is associated with lipid metabolism and dyslipidemia and that, the inhibition of its activity, can reduce translation of genes linked to atherosclerosis and at extracellular level, improve availability of hepatic receptors linked to the lipid residue clearance associated with apolipoprotein E. From this work it is evident that there’s a lack of studies like clinical trials, to envision heparanase inhibitors effect on lipid metabolism disorders, as they can prove to be an asset in the approach to dyslipidemia and its consequences.
Introduction: Heparanase is an enzyme capable of degrading heparano-sulfate chains, these chains are an integral part of heparano-sulfate proteoglycans which are expressed in extracellular matrix. This complex enzyme seems to have enzymatic and non-enzymatic roles whether it be extra or intracellularly. Amongst the different actions of heparanase, it demonstrates interactions at the level of lipid metabolism. Dyslipidemia has a growing prevalence in the Portuguese population. Being a pleiotropic enzyme, heparanase displays a potencial therapeutic target, that might turn into an add-on option against dyslipidemia in the midst of primary or secondary prevention. Objectives: The main objective is gathering, organising and summarization information regarding various discoveries about heparanase, regarding lipid metabolism so as to understand the potential of the enzyme as a therapeutic target in dyslipidemia. Methodology: Literature review was made through a search on Medlines data base using the research engine PubMed, as well as Cochrane and Web of Science Core Collection data basis with the expressions heparinase and cholesterol refined with heparinase inhibitors. From these results, articles written from 1990 to 2021, redacted in English and Portuguese were selected. Complementary to these sources, guidelines of European Society of Cardiology, a Portuguese study from Instituto Ricardo Jorge and manuals of Clinical Medicine namely, Manual Oxford of Clinical Medicine were consulted in the makings of this work. Conclusion: This work concludes that heparanase is associated with lipid metabolism and dyslipidemia and that, the inhibition of its activity, can reduce translation of genes linked to atherosclerosis and at extracellular level, improve availability of hepatic receptors linked to the lipid residue clearance associated with apolipoprotein E. From this work it is evident that there’s a lack of studies like clinical trials, to envision heparanase inhibitors effect on lipid metabolism disorders, as they can prove to be an asset in the approach to dyslipidemia and its consequences.
Descrição
Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2022
Palavras-chave
Heparanase Proteoglicanos de sulfato de heparano (HSPG) Inibidores da heparanase Apolipoproteína E Dislipidemia