Dottorato in MEDICINA SPERIMENTALE

Titolo della tesi: Identification of events predicting progression vascular lesions in the Takayasu’s arteritis

Takayasu's arteritis (TA) is a very rare chronic vasculitis characterized by a chronic inflammation of the aorta and its main branches. This disease can be divided into two phases. The first, acute phase is characterized by the presence of granulomatous lesions, transmural inflammation and destruction of the musculo-elastic lamina. The second, phase of remission or frost is characterized by the onset of adventitial and intimal fibrosis with extensive scarring of the tunica media. Data from the literature suggests that the activation status and metabolic characteristics of peripheral blood mononuclear cells (PBMCs) may reflect vessel wall remodeling and predict clues to vascular injury progression. The main objective of this study was to identify cellular and soluble biomarkers related to the progression of vascular damage. To achieve this aim, ex vivo and in vitro studies were performed. Frozen serum and resting PBMCs from patients in various stages of disease (inactive, grumbling and active), were used for the ex vivo studies. Cellular homeostasis was analyzed through flow cytometry analysis. In particular, superoxide anion and hydrogen peroxide content was measured. Furthermore, molecules involved in cell death (apoptosis) and survival (autophagy) were analyzed by Western Blot. For in vitro studies, on the other hand, primary endothelial cells from female umbilical cord (HUVECs) were used. These cells were treated with 20% of the serum of TA patients in order to evaluated endothelial damage induced by inflammatory proteins present in patient serum. Data obtained suggest two new markers that can be used in the early diagnosis of vascular lesions in TA: high levels of soluble LOX-1 and high percentages of apoptotic PMBCs.