Ianni Alessandro, Kumari Poonam, Tarighi Shahriar, Argento Flavia Rita, Fini Eleonora, Emmi Giacomo, Bettiol Alessandra, Braun Thomas, Prisco Domenico, Fiorillo Claudia, Becatti Matteo
Department of Cardiac Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany.
Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Firenze, 50134 Firenze, Italy.
Antioxidants (Basel). 2021 May 31;10(6):885. doi: 10.3390/antiox10060885.
Giant cell arteritis (GCA), medium and large vessel granulomatous vasculitis affecting the elderly, is characterized by a multitude of vascular complications, including venous thrombosis, myocardial infraction and stroke. The formation of granulomatous infiltrates and the enhanced accumulation of proinflammatory cytokines are typical features of this condition. The GCA pathogenesis remains largely unknown, but recent studies have suggested the involvement of oxidative stress, mainly sustained by an enhanced reactive oxygen species (ROS) production by immature neutrophils. On this basis, in the present study, we intended to evaluate, in GCA patients, the presence of systemic oxidative stress and possible alterations in the expression level of nuclear sirtuins, enzymes involved in the inhibition of inflammation and oxidative stress. Thirty GCA patients were included in the study and compared to 30 healthy controls in terms of leukocyte ROS production, oxidative stress and SIRT1 expression. Our results clearly indicated a significant increase ( < 0.05) both in the ROS levels in the leukocyte fractions and plasma oxidative stress markers (lipid peroxidation and total antioxidant capacity) in the GCA patients compared to the healthy controls. In PBMCs from the GCA patients, a significant decrease in SIRT1 expression ( < 0.05) but not in SIRT6 and SIRT7 expression was found. Taken together, our preliminary findings indicate that, in GCA patients, plasma oxidative stress is paralleled by a reduced SIRT1 expression in PBMC. Further studies are needed to highlight if and how these alterations contribute to GCA pathogenesis.
巨细胞动脉炎（GCA）是一种影响老年人的中大型血管肉芽肿性血管炎，其特征是有多种血管并发症，包括静脉血栓形成、心肌梗死和中风。肉芽肿浸润的形成以及促炎细胞因子积累的增加是这种疾病的典型特征。GCA的发病机制在很大程度上仍然未知，但最近的研究表明氧化应激参与其中，主要由未成熟中性粒细胞产生的活性氧（ROS）增加所维持。在此基础上，在本研究中，我们旨在评估GCA患者全身氧化应激的存在情况以及参与炎症和氧化应激抑制的核沉默调节蛋白表达水平的可能变化。30例GCA患者被纳入研究，并与30例健康对照在白细胞ROS产生、氧化应激和SIRT1表达方面进行比较。我们的结果清楚地表明，与健康对照相比，GCA患者白细胞部分的ROS水平和血浆氧化应激标志物（脂质过氧化和总抗氧化能力）均显著升高（<0.05）。在GCA患者的外周血单核细胞（PBMC）中，发现SIRT1表达显著降低（<0.05），但SIRT6和SIRT7表达未降低。综上所述，我们的初步研究结果表明，在GCA患者中，血浆氧化应激与PBMC中SIRT1表达降低并行。需要进一步研究以突出这些变化是否以及如何导致GCA发病机制。
