Metabolic characterization of endothelial cells dysfunctionality associated to acute myocardial infarction

<p>Atherosclerosis is a disease associated with premature biological aging,<sup> [1]</sup> as atherosclerotic plaques show evidence of cellular senescence. Emerging evidences indicate that pathological blood vessel responses and dysfunctionality of Endothelial Cells (ECs) are associated with metabolic alterations and can be considered a primary factor in the onset and progression of atherosclerosis and other vascular related diseases, such as acute myocardial infarction. This is a leading cause of morbidity worldwide and occurs when myocardial ischemia exceeds a critical threshold and overcomes myocardial cellular repair mechanisms designed to maintain normal function and homeostasis. Preliminary data from our group have suggested that ECs derived from acute myocardial infarction patients show an altered phenotype with lower proliferation and contribute to neovascularization.</p> <p>In this study we aim to establish an <em>in vitro</em> model of endothelial pathology using patient-derived endothelial cell lines which are subjected to a systematic evaluation against control cells,<sup> [2]</sup> to determine the metabolic profile and deep investigate if the endothelial dysfunctionality is a consequence of an abnormal endothelial cell metabolism. The recent results obtained are a part of this attempt, and include a preliminary study of cells growth and of its ability in migration. This study also aims at performing a complete characterization of the metabolic profiles of ECs in normal and pathological conditions, and will include an integrated systems biology approach and proteomic analysis. The identification of novel therapeutic targets to enhance endothelial function and prevent acute myocardial syndrome is one of the principal objectives of our research.</p> <p>[1] J.Goveia, P.Stapor, P.Carmeliet “Principles of targeting endothelial cell metabolism to treat angiogenesis and endothelial cell dysfunction in disease” <em>EMBO Molecular Medicine</em>. <strong>2014</strong>; 6(9):1105-20</p> <p>[2] Mills NL, Tura O, Padfield GJ, Millar C, Lang NN, Stirling D, Ludlam C, Turner ML, Barclay GR, Newby DE. “Dissociation of phenotypic and functional endothelial progenitor cells in patients undergoing percutaneous coronary intervention.” <em>Heart,</em> <strong>2009</strong>; 95(24):2003-8</p> <p><em>This work was supported by funds</em> <em>of </em><em>European Union’s Horizon MOGLYNET (grant agreement nº 6755279); AGAUR – Generalitat de Catalunya (2014SGR1017); M.C. acknowledges the support received through “ICREA Academia” (ICREA foundation – Generalitat de Catalunya).</em></p>