AbstractsBiology & Animal Science

Persistence of inflammatory activity in giant cell arteritis:Role of the angiotensin II system

by Marco Antonio Alba Garibay

Institution: Universitat de Barcelona
Year: 2014
Keywords: Vasculitis; Inflamació; Inflamación; Inflammation; Angiotensina; Angiotensin; Ciències de la Salut
Record ID: 1124373
Full text PDF: http://hdl.handle.net/10803/283754


Giant cell arteritis (GCA) is a systemic vasculitis of unknown aetiology that affects medium-sized and large arteries. GCA may deeply impair the patient's quality of life as a result of systemic smouldering activity, disease progression or adverse effects related to therapy. The present thesis is a compendium of four articles assessing clinical and immunopathological characteristics associated with persistence of chronic inflammation in GCA patients. In the first publication, we described the clinical course of a small series of GCA patients derived from Latin America, a geographic area where data regarding this disease were virtually absent. We found that major features observed in this population were similar to those reported in series of Caucasian origin. The second article described the prevalence, predictors, and main features of relapses, one of the many faces of the persistent inflammatory activity that characterizes GCA. This study, performed in a large cohort of patients uniformly treated and followed, demonstrated that disease flares are frequent and, importantly, that a relapsing course was associated with higher and prolonged GC requirements and increased morbidity. The third publication was oriented to the need of identifying adjuvant therapies for GCA and deals with the potential benefit of adding angiotensin II receptor blockers (ARB) to standard prednisone treatment. The study rationale was based on the pleiotropic anti-inflammatory effects recently described for this drug class. Our results suggest that ATII receptor blockade may help to maintain remission, reduce the relapse rate, and spare glucocorticoids in patients with GCA. Following this clinical observation, we further investigated a potential contribution of the angiotensin II (ATII) system in the maintenance of inflammatory activity in GCA. In the fourth paper we showed that ATII system is overexpressed in GCA inflammatory lesions. In addition, we confirmed that ATII exhibited pro-inflammatory properties in co-cultures of Iymphocytes, monocytes and temporal artery-derived vascular smooth muscle cells which were reversed by the angiotensin II receptor blocker losartan..; La arteritis de células gigantes (ACG) es una vasculitis sistémica idiopática que afecta principalmente arterias de mediano y gran calibre. La calidad de vida de estos pacientes puede verse seriamente afectada debido a múltiples complicaciones inmediatas y tardías. Esta tesis es un compendio de cuatro artículos que evalúan características clínicas e inmunopatológicas de la persistencia de la inflamación crónica en la ACG. En la primera publicación, se describen las características y la evolución de la enfermedad en una pequeña serie de pacientes latinoamericanos, concluyéndose que las manifestaciones y el comportamiento de esta vasculitis es similar a la reportada en otras cohortes, principalmente de origen caucásico. En el segundo artículo se describe la prevalencia, características y factores asociados con las recaídas o rebrotes, una manifestación de la constante…