Article Text

AB0271 Effects of Glucocorticoids on Endothelial Function: Focus on Rheumatoid Arthritis
  1. F. Verhoeven1,2,
  2. C. Prati1,2,
  3. D. Wendling2,3,
  4. C. Demougeot1
  1. 1EA 4267 “fonctions et dysfonctions épithéliales”, UFR SMP, université de Franche Comté
  2. 2Rhumatologie, CHRU de Besançon
  3. 3EA 4266 “agents pathogenes et inflammation”, UFR SMP, université de Franche Comté, Besançon, France


Background Rheumatoid arthritis (RA) is the most common systemic autoimmune disease characterized by reduced life expectancy due to accelerated atherogenesis. Endothelial dysfunction (ED) precedes and initiates atherosclerosis, and its correction is associated with reduced CV risk. ED is present in RA and appears as a seminal target for reducing CV risk in RA. Despite the dramatic changes that occurred in the treatment approach in RA, majority of patients still use glucocorticoids (GCs). The potential harmful CV effects of GCs are “well-known” in the general population. In inflammatory diseases such as RA, the effects of GCs on CV risk is still a matter of debate. On the one hand, GC might increase CV risk by increasing CV risk factors but on the other hand, GC might reduce CV risk by decreasing the systemic and/or vascular inflammation.

Objectives To provide the available data regarding the effects of GC on endothelial function, with a special focus on RA.

Methods Systematic review of the literature on the PubMed database with the following keywords: “Glucocorticoids”, “rheumatoid arthritis”, “endothelial function” and “vascular function”.

Results In the vascular system, GC receptors are expressed by intact arteries, cultured vascular smooth muscle cells (VSMC) and endothelial cells. In physiological conditions, experimental data provide evidence of harmful effects of GCs on endothelial function, due to decreased Nitric oxide synthase activity/expression, decreased production of endothelium-derived hyperpolarizing factor (EDHF) and prostacyclin, the three main vasorelaxant endothelium-derived factors, associated with increased production of endothelin-1, an endothelium-derived vasoconstrictor. These experimental data were not unanimously confirmed by the few studies in healthy controls, which reported negative or not effect of GCs on endothelial function. Effect of GCs is totally different in inflammatory conditions in which GC reduced endothelial dysfunction and slowed progression of atherosclerotic plaques in animal models. Only 6 clinical studies were performed in RA. The available data suggested that low dose GC (5 mg/d) did not change endothelial function while a high dose for a short period (7 days) improved endothelial function in RA patient. No harmful effect of GC on endothelial function were reported in RA.

Conclusions Data from experimental models highlighted the Janus face of GCs since they can exert deleterious effects on endothelial function when applied in “normal” cells/animals although they seem to be protective under inflammatory conditions. In RA patients, data are scarce and highly controversial due to methodological weaknesses. However, contrary to common believe that GCs deteriorate CV function, no effect and even positive effect of GCs on endothelial function have been reported. As more RA patients are starting GCs early in their disease course, there is an urgent need to perform clinical trials specifically-designed to define the best GCs strategy to prevent CV risk in RA.

Disclosure of Interest None declared

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