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Objective: The pathophysiology of giant cell arteritis (GCA) and the mechanisms underlying vascular remodeling, are poorly understood. We aimed to compare vascular smooth muscle cells (VSMCs) from patients with GCA and controls by a proteomic and gene expression profile approach and to identify the signaling pathways involved in proliferation., Methods: VSMCs were cultured from temporal artery biopsies (TABs) from patients with biopsy-proven GCA (TAB + -GCA), biopsy-negative GCA (TAB - -GCA), and diagnosis other than GCA (GCA-control). VSMCs from normal human aorta (HAoSMC) were used as controls. 2D-differential in-gel electrophoresis and Affymetrix chips were used to compare proteomes and gene expression profiles of VSMCs. Proliferation was assessed by BrdU incorporation assay. TAB + -GCA and GCA-control TABs underwent immunohistochemistry staining for endothelin-1 (ET-1) and receptors ET A R and ET B R., Results: We identified 16, 30 and 2 protein spots differentially expressed between TAB + -GCA and GCA-control VSMCs, TAB + -GCA and TAB - -GCA VSMCs and TAB - -GCA and GCA-control VSMCs, respectively (fold change ≥1.5 and p≤0.05). Among the 153 proteins differentially expressed between TAB + -GCA and HAoSMC VSMCs, many were linked with ET-1. Genes differentially expressed between TAB + -GCA and GCA-control VSMCs were involved in proliferation. ET-1 was identified as a link between genes of interest. Proliferation was reduced for TAB + -GCA VSMCs on treatment with the endothelin antagonist macitentan and its active metabolite. Patients showing transmural expression of ET-1 in temporal artery lesions received a significantly higher glucocorticoid daily dose after 6-month follow-up., Conclusion: Inhibiting the proliferation with macitentan, combined with glucocorticoids, might be a promising therapeutic approach for patients with GCA., (Copyright © 2017 Elsevier B.V. All rights reserved.)

ANCA-associated vasculitis (AAV) is a subgroup of vasculitides characterized by the detection of anti-neutrophil cytoplasm antibodies (ANCA). Until recently, the pathogenesis of AAV mainly involved neutrophils, T cells, and ANCA. Importantly, data were recently published supporting B-cell implication in this setting. Thus, the identification of activated B lymphocytes in granulomatous lesions and the efficacy of B-cell depletion using rituximab in the treatment of patients with AAV changed our mind. However, the impact of B lymphocytes on disease activity and its specific role in the pathogenesis of AAV remains unclear, at least in part as the consequence of the limited number of patients investigated and the restricted number of studies investigating B-cell subsets. Perturbations of B-cell homeostasis have been identified in AAV with increased expression of CD38 and decreased expression of CD5 in active phase, contrasting with increased expression of CD25 and CD86 in remission state. Although decreased secretion of interleukin (IL)-10 has also been reported during disease flares, these data remain controversial and the cytokines secretion profile of B-cells needs to be further investigated. Herein, we summarize recent advances in the understanding of the implications of B-cells in the field of AAV and propose new fields of investigation for a better understanding of B lymphocytes in the pathogenesis of AAV., (Copyright © 2015 Elsevier B.V. All rights reserved.)