Objective: About 15- 20 % of patients with giant-cell arteritis (GCA) develop ischemic complications often preceded by transient ischemia. We investigated the expression of the endothelin (ET) system in GCA lesions, to assess its relationship with the development of ischemic complications.
Methods: Plasma ET-1 was quantified by immunoassay in 61 patients with biopsy-proven GCA and 16 healthy donors. ET-1, endothelin converting enzyme (ECE-1) and ET receptor (ETAR and ETBR) mRNAs were measured by real-time quantitative RT-PCR in temporal arteries from 35 of these patients and 19 control arteries. Proteins were measured by immunoassay and western-blot.
Results: ET-1 concentration was increased at the protein level in temporal artery samples from GCA patients compared to controls (0.28±0.098 [x±SEM] vs 0.98±0.32 fmol/mg, p=0.028). ECE-1, ETAR and ETBR /actin ratios (western-blot) were also significantly higher in GCA patients. Intriguingly, mRNA expression of ET-1, ECE-1 and both receptors was significantly reduced in GCA lesions compared to control arteries. When investigating mechanisms underlying these results, we found that PDGF and IL-1β, present in GCA lesions, down-regulated ET-1 mRNA in cultured human temporal artery-derived smooth muscle cells. Glucocorticoid treatment for 8 days did not result in significantly decreased ET tissue concentration (0.87±0.2 vs 0.52±0.08;p=0.6). Plasma ET concentrations were higher in patients with ischemic complications (1.049±0.48 vs 1.205±0.63 pg/mL,p= 0.032).
Conclusions: The ET system is increased at the protein level in GCA lesions creating a microenvironment prone to the development of ischemic complications. Recovery induced by glucocorticoids is delayed, indicating persistent exposure to ET during initial treatment.
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