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Quiescin sulfhydryl oxidase (QSOX) is expressed in the human atheroma core: possible role in apoptosis

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Abstract

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.

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Acknowledgments

This work was supported by FAPESP, CAPES, and CNPq (Institutos do Milenio Redoxoma).

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Author notes

  1. Claudia R. de Andrade

    Present address: Biology of Reproduction Laboratory, Department of Animal Science, Federal University of Ceara (UFC), Avenida Mr Hull s/n, CEP 60365-001, Fortaleza, Ceará, Brazil

  2. Beatriz S. Stolf

    Present address: Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil

Authors and Affiliations

  1. Vascular Biology Laboratory, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil

    Claudia R. de Andrade, Victor Debbas & Francisco R. M. Laurindo

  2. Laboratory of Immunology, Heart Institute (InCor), Medical School, University of São Paulo, São Paulo, Brazil

    Beatriz S. Stolf, Jorge Kalil & Veronica Coelho

  3. Laboratory of Clinical Immunology and Allergy (LIM-60), Department of Clinical Medicine, University of São Paulo, São Paulo, Brazil

    Daniela S. Rosa

  4. INCT–Institute for Investigation in Immunology–National Institute of Science and Technology, São Paulo, Brazil

    Jorge Kalil & Veronica Coelho

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  1. Claudia R. de Andrade
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Correspondence to Claudia R. de Andrade.

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Editor: T. Okamoto

Claudia R. de Andrade and Beatriz S. Stolf contributed equally to this work.

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de Andrade, C.R., Stolf, B.S., Debbas, V. et al. Quiescin sulfhydryl oxidase (QSOX) is expressed in the human atheroma core: possible role in apoptosis. In Vitro Cell.Dev.Biol.-Animal 47, 716–727 (2011). https://doi.org/10.1007/s11626-011-9461-0

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