Objective. Giant cell arteritis (GCA) is pathologically characterized by dysfunctional angiogenesis and inflammatory cell infiltration. Acute-phase serum amyloid A (A-SAA) is an acute-phase reactant, but is also produced at sites of inflammation and may contribute to vascular inflammation in atherosclerosis. This study was undertaken to examine the effect of A-SAA on proinflammatory pathways and angiogenesis in GCA, using a novel ex vivo temporal artery tissue explant model.Methods. Serum A-SAA levels were measured by enzyme-linked immunosorbent assay (ELISA). Temporal artery explants and peripheral blood mononuclear cell (PBMC) cultures were established from patients with GCA. Temporal artery explant morphology, viability, and spontaneous release of proinflammatory mediators following 24-hour culture were assessed by hematoxylin and eosin, calcein viability staining, and ELISA. Temporal artery explants and PBMC cultures were stimulated with A-SAA (10 mg/ml), and interleukin-6 (IL-6), IL-8, vascular endothelial growth factor, Ang2, and matrix metalloproteinase 2 (MMP-2)/MMP-9 were quantified by ELISA and gelatin zymography. The effect of conditioned medium from temporal artery explants on angiogenesis was assessed using endothelial cell Matrigel tube-formation assays. Temporal artery explants were also embedded in Matrigel, and myofibroblast outgrowth was assessed.Results. Serum A-SAA levels were significantly higher in GCA patients versus healthy controls (P < 0.0001). Intact tissue morphology, cell viability, and spontaneous cytokine secretion were demonstrated in temporal artery explants. A-SAA treatment induced a significant increase in the levels of IL-6 and IL-8 from temporal artery explants (P < 0.05) and IL-8 from PBMCs (P < 0.05) compared to basal conditions. Conditioned medium from A-SAA-treated explants significantly induced angiogenic tube formation (P < 0.05 versus basal controls). Finally, A-SAA induced myofibroblast outgrowth and MMP-9 activation.Conclusion. Our findings demonstrate a functional role for A-SAA in regulating temporal artery inflammation, angiogenesis, and invasion, all key processes in the pathogenesis of GCA.Giant cell arteritis (GCA) is the most common form of primary systemic vasculitis, affecting medium to large arteries, with a predilection for the temporal, carotid, axillary, and subclavian arteries and the thoracic aorta. Disease-related complications include blindness, stroke, and aortic dissection and rupture. Patients with GCA currently require treatment with high-dose glucocorticoids (GCs) for a prolonged period of time. Consequently, serious GC-related toxicity, including osteoporosis with fractures, diabetes mellitus, and infections are common and have been described in up to 86% of GCA patients in one large series (1). Other immunosuppressive agents, such as methotrexate and tumor necrosis factor (TNF) inhibitors, have shown disappointing results in randomized controlled trials in GCA patients

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In normotensive postmenopausal women, replacement doses of natural and semisynthetic oestrogen reduce night-time ambulatory blood pressure with either no change or a small reduction in clinic blood pressure. Reduction in blood pressure is not explained by reduced activity of the renin-angiotensin system but could have a component of reduced central sympathetic drive consistent with the decreased heart rate.

Thirty-three patients were prescribed PPIs; 26 prior to admission. The prescribing of PPIs was concordant with guideline recommendations in only 30% of cases. Two-thirds of PPI use was unlicensed.