Vascular Biology Laboratory, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil.
In Vitro Cell Dev Biol Anim. 2011 Dec;47(10):716-27. doi: 10.1007/s11626-011-9461-0. Epub 2011 Nov 9.
Quiescin sulfhydryl oxidases (QSOXs) catalyze the formation of disulfide bonds in peptides and proteins, and in vertebrates comprise two proteins: QSOX1 and QSOX2. QSOX1, the most extensively studied type, has been implicated in protein folding, production of extracellular matrix, redox regulation, protection from apoptosis, angiogenesis, and cell differentiation. Atherosclerosis is an immunopathological condition in which redox processes, apoptosis, cell differentiation, and matrix secretion/maturation have critical roles. Considering these data, we hypothesized that QSOX1 could be involved in this disease, possibly reducing apoptosis and angiogenesis inside the plaque. QSOX1 labeling in normal human carotid vessels showed predominant expression by endothelium, subendothelium, and adventitia. In atherosclerotic plaques, however, QSOX1 was highly expressed in macrophages at the lipid core. QSOX1 expression was also studied in terms of mRNA and protein in cell types present in plaques under apoptotic or activating stimuli, emulating conditions found in the atherosclerotic process. QSOX1 mRNA increased in endothelial cells and macrophages after the induction of apoptosis. At the protein level, the correlation between apoptosis and QSOX1 expression was not evident in all cell types, possibly because of a rapid secretion of QSOX1. Our results propose for the first time possible roles for QSOX1 in atherosclerosis, being upregulated in endothelial cells and macrophages by apoptosis and cell activation, and possibly controlling these processes, as well as angiogenesis. The quantitative differences in QSOX1 induction may depend on the cell type and also on local factors.
去巯基氧化酶（QSOXs）催化肽和蛋白质中二硫键的形成，脊椎动物中包含两种蛋白质：QSOX1 和 QSOX2。QSOX1 是研究最广泛的一种，它与蛋白质折叠、细胞外基质的产生、氧化还原调节、细胞凋亡的保护、血管生成和细胞分化有关。动脉粥样硬化是一种免疫病理学疾病，其中氧化还原过程、细胞凋亡、细胞分化和基质分泌/成熟起着关键作用。考虑到这些数据，我们假设 QSOX1 可能与这种疾病有关，可能会减少斑块内的细胞凋亡和血管生成。QSOX1 在正常人类颈动脉血管中的标记显示主要由内皮细胞、内皮下层和外膜表达。然而，在动脉粥样硬化斑块中，QSOX1 在脂质核心中的巨噬细胞中高度表达。还研究了 QSOX1 在斑块中存在的细胞类型在凋亡或激活刺激下的 mRNA 和蛋白质表达，模拟了动脉粥样硬化过程中发现的条件。在诱导细胞凋亡后，内皮细胞和巨噬细胞中的 QSOX1mRNA 增加。在蛋白质水平上，在所有细胞类型中，细胞凋亡与 QSOX1 表达之间的相关性并不明显，这可能是因为 QSOX1 迅速分泌。我们的研究结果首次提出 QSOX1 在动脉粥样硬化中的可能作用，在细胞凋亡和细胞激活时在内皮细胞和巨噬细胞中上调，并可能控制这些过程以及血管生成。QSOX1 诱导的定量差异可能取决于细胞类型和局部因素。
