RESUMO
Restenosis remains the main complication after percutaneous coronary interventions in patients with coronary heart disease. The causes of its development include, in particular, genetic factors. We studied polymorphic loci of genes encoding endothelin-1 (EDN1 rs5370), endothelin-1 receptor (EDNRA rs5333), endothelin-converting enzyme (ECE1 rs1076669), and endothelial NO synthase (eNOS rs1549758, eNOS rs1799983, and eNOS rs2070244) in the context of in-stent restenosis development. It was found that the analyzed polymorphisms of the endothelin system genes were more significant for patients aged ≥ 65 years, while the polymorphic loci of the endothelial NO synthase gene (eNOS rs1799983 and eNOS rs1549758) were predominantly associated with time of in-stent restenosis. The obtained results can be useful for comprehensive assessment of the restenosis risk factors and the choice of optimal treatment for patients with coronary heart disease before elective surgical intervention.
Assuntos
Doença da Artéria Coronariana , Oclusão de Enxerto Vascular/genética , Intervenção Coronária Percutânea/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/cirurgia , Vasos Coronários/metabolismo , Vasos Coronários/patologia , Vasos Coronários/cirurgia , Endotelina-1/genética , Enzimas Conversoras de Endotelina/genética , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Oclusão de Enxerto Vascular/epidemiologia , Humanos , Masculino , Neovascularização Patológica/epidemiologia , Neovascularização Patológica/genética , Óxido Nítrico Sintase Tipo III/genética , Polimorfismo de Nucleotídeo Único , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/genética , Receptor de Endotelina A/genética , Stents/efeitos adversosRESUMO
Large investments by pharmaceutical companies in the development of new antineoplastic drugs have not been resulting in adequate advances of new therapies. Despite the introduction of new methods, technologies, translational medicine and bioinformatics, the usage of collected knowledge is unsatisfactory. In this paper, using examples of pancreatic ductal adenocarcinoma (PaC) and castrate-resistant prostate cancer (CRPC), we proposed a concept showing that, in order to improve applicability of current knowledge in oncology, the re-clustering of clinical and scientific data is crucial. Such an approach, based on systems oncology, would include bridging of data on biomarkers and pathways between different cancer types. Proposed concept would introduce a new matrix, which enables combining of already approved therapies between cancer types. Paper provides a (a) detailed analysis of similarities in mechanisms of etiology and progression between PaC and CRPC, (b) diabetes as common hallmark of both cancer types and (c) knowledge gaps and directions of future investigations. Proposed horizontal and vertical matrix in cancer profiling has potency to improve current antineoplastic therapy efficacy. Systems biology map using Systems Biology Graphical Notation Language is used for summarizing complex interactions and similarities of mechanisms in biology of PaC and CRPC.
