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- Role of fatty acid oxidation in quiescent endothelial cellsPublication . Conchinha, Nadine VasconcelosEndothelial cells (ECs) are located in the innermost layer of blood vessels and are in direct contact with the blood stream. ECs in established, healthy blood vessels are quiescent and most of them can stay in their quiescent state for many years but when stimulated under physiological or pathological conditions, they become proliferative and allow vessel growth (process called angiogenesis). Due to their key localization, ECs are involved in many different functions like fluid filtration, blood vessel tone, homeostasis and oxygen and nutrients supply. Thus, it is not surprising that when ECs become dysfunctional, they contribute to a large range of diseases like hypertension, atherosclerosis, thrombosis, leakage, stroke, tissue ischemia, etc. The host lab already characterized some metabolic features of proliferating ECs that are affecting sprouting and migration of ECs cells. These studies showed that EC metabolism could be a promising target for anti-angiogenesis therapies. However, in spite of recent advances, the metabolism of the quiescent endothelium remains incompletely understood. In this project we sought to study the metabolic changes facilitating the switch from proliferating to quiescent ECs. Our first results showed that during this switch glucose oxidation and glycolytic flux are reduced, whereas fatty acid ß-oxidation (FAO) is increased. As quiescent ECs are exposed to an oxygen-rich microenvironment, we hypothesize that the FAO derived acetyl-CoA fuels the TCA cycle to produce NADPH to preserve the redox homeostasis of the cell. Mechanistically, activation of Notch signaling pathway regulate the induction of the metabolic changes in quiescent ECs.