RT Dissertation/Thesis
T1 Role of Tie2 in vascular damage observed in Systemic Lupus Erythematosus and Rheumatoid Arthritis
T2 Papel de Tie2 no dano vascular observado no lupus eritematoso sistémico e na artrite reumatoide
A1 Rafael Vidal, Carlos
K1 3205 Medicina Interna
K1 3207.10 Inmunopatología
AB Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with an incidence in Spain of 1.9-3.6 cases/year per 100,000 individuals and a prevalence of 0.21% and is characterised by the production of auto-antibodies and the formation and deposition of immune complexes that induce systemic inflammation and tissue damage. In this regard, it is important to note that cardiovascular events (CVE) are more frequent in lupus patients than in healthy controls and these events are currently one of the most important causes of death among patients with SLE. Rheumatoid arthritis (RA) is a systemic autoimmune rheumatic disease characterised by peripheral joint inflammation, bone erosion and cartilage destruction, resulting in functional disability. Patients with RA also have an increased risk of developing cardiovascular events compared to the general population. Importantly, in RA, classical cardiovascular risk factors play a predominant role, but, as in SLE, non-traditional factors play a role in increasing the risk of cardiovascular events, which are not yet well understood.Tie2 is a tyrosine kinase receptor that, through interaction with its ligands angiopoietin-1 (Ang-1) and Ang-2, plays an essential role in vascular development, both in the stabilisation and remodelling of existing vasculature and in the formation of new blood vessels (angiogenesis). Under homeostatic conditions, both Ang-1 and Ang-2 activate Tie2 signalling and induce vascular stabilisation. However, inflammatory processes induce cleavage of Tie1, which is another member of the Tie2 family. This cleavage leads to inhibition of Ang-1-induced Tie2 activation and increased Ang-2 levels. In this inflammatory environment Ang-2 acts as a Tie2 antagonist, inducing endothelial cell (EC) activation and ultimately vascular dysfunction.We hypothesise that altered Tie2 signalling is involved in the endothelial dysfunction observed in patients with systemic lupus erythematosus and rheumatoid arthritis, and that Tie2 could be a novel therapeutic target for the prevention of cardiovascular events in these patients.ObjectivesObjective 1. To determine the use of the Tie-Angs system as a biomarker of risk of vascular damage in patients with SLE.Objective 2. To analyse the effect of type I interferon on Ang-1 expression by peripheral blood mononuclear cells (PBMCs) and monocytes from patients with SLE.Objective 3. To determine whether the inflammatory processes observed in patients with SLE are responsible for the imbalance in Tie2 signalling and to analyse the functional consequences of this imbalance.Objective 4. To phenotypically characterise endothelial progenitor cell (EPCs) populations in patients with SLE.Objective 5. To determine whether TNF-alpha is responsible for the imbalance in Tie/Angiopoietin signalling in patients with RA, to analyse the functional consequences and its link to the cardiovascular events observed in these patients.
LK http://hdl.handle.net/11093/7195
UL http://hdl.handle.net/11093/7195
LA spa
DS Investigo
RD 10-sep-2024