Inflammation, thrombosis and endothelial dysfunction in myocardial infarction

Tese de doutoramento, Biologia (Fisiologia e Bioquímica), 2009, Universidade de Lisboa, Faculdade de CiênciasThe aim of this study was to investigate the association between different processes implicated in acute myocardial infarction (AMI), such as inflammation, thrombosis, immune response and endothelial dysfunction, at different phases of the disease. Thus, a follow-up of 50 AMI patients was evaluated at 3 time points: at admission before the administration of IIb/IIIa inhibitors and angioplasty, 2 days and 40 days after. A group of 25 healthy volunteers was used as reference (REF). The higher concentrations of ox-LDL at AMI onset were suggested to be related to plaque instability. Furthermore, the serial changes of ox-LDL were associated with CAD severity and eventually to lesion characteristics depending on the infarct-related artery. The results also highlight the great magnitude of the thrombotic process associated to plaque disruption at AMI onset that conceals possible variations of platelet-related thrombosis markers, mainly expressed by CD40L. Additionally, the results emphasize the importance of the inflammatory response that remains after clinical stabilization as given by the interplay of TNF-α, sICAM-1, sP-selectin, CD40L, leukocytes, NO and EMPs. Importantly, the results of sCD40L longitudinal variations allowed the differentiation of two groups of AMI patients, which also differed in NT-proBNP concentrations but did not shown variations in terms of risk factors and co-morbidities, nor influence of drug intake. This is the first study evaluating the inter-relationships between markers of inflammation, thrombosis, immune response and endothelial damage using multi-parameter longitudinal approach. The results revealed the interplay between those mechanisms and their relative importance in each phase of the disease. In conclusion, the work allowed a better understanding of the complex relationships between the studied markers involved in the different phases of AMI evolution, decisively contributing to a better understand of the pathology and mechanisms of AMI.Resumo alargado em português disponível no documentoEstudo foi co-financiado pela Fundação para a Ciência e Tecnologia (SFRHI/BD/18822/2004) através dos programas de financiamento POCI 2010 e FS