Oxidized LDL induces a coordinated up-regulation of the glutathione and thioredoxin systems in human macrophages

Hägg, Daniel; Englund, Mikael C.O.; Jernås, Margareta; Schmidt, Caroline; Wiklund, Olov; Hultén, Lillemor Mattsson; Ohlsson, Bertil G.; Carlsson, Lena M.S.; Carlsson, Björn; Svensson, Per-Arne

doi:10.1016/j.atherosclerosis.2005.06.034

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Volume 185, Issue 2 , Pages 282-289, April 2006

Oxidized LDL induces a coordinated up-regulation of the glutathione and thioredoxin systems in human macrophages

Daniel Hägg
- Research Centre for Endocrinology and Metabolism, Division of Body Composition and Metabolism, Department of Internal Medicine, Vita stråket 15, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden
- Corresponding author. Tel.: +46 31 342 40 46; fax: +46 31 41 85 27.
Mikael C.O. Englund
- Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden
Margareta Jernås
- Research Centre for Endocrinology and Metabolism, Division of Body Composition and Metabolism, Department of Internal Medicine, Vita stråket 15, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden
Caroline Schmidt
- Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden
Olov Wiklund
- Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden
Lillemor Mattsson Hultén
- Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden
Bertil G. Ohlsson
- Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden
Lena M.S. Carlsson
- Research Centre for Endocrinology and Metabolism, Division of Body Composition and Metabolism, Department of Internal Medicine, Vita stråket 15, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden
Björn Carlsson
- Research Centre for Endocrinology and Metabolism, Division of Body Composition and Metabolism, Department of Internal Medicine, Vita stråket 15, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden
Per-Arne Svensson
- Research Centre for Endocrinology and Metabolism, Division of Body Composition and Metabolism, Department of Internal Medicine, Vita stråket 15, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden
- Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden

Received 12 April 2005; received in revised form 14 June 2005; accepted 21 June 2005. published online 27 July 2005.

Abstract

Using DNA microarray analysis, we found that human macrophages respond to oxidized low-density lipoprotein (oxLDL) by activating the antioxidative glutathione and thioredoxin systems. Several genes of the glutathione and thioredoxin systems were expressed at high levels in macrophages when compared to 80 other human tissues and cell types, indicating that these systems may be of particular importance in macrophages. The up-regulation of three genes in these systems, thioredoxin (P<0.005), thioredoxin reductase 1 (P<0.001) and glutathione reductase (P<0.001) was verified with real-time RT-PCR, using human macrophages from 10 healthy donors. To investigate the possible role of these antioxidative systems in the development of atherosclerosis, expression levels in macrophages from 15 subjects with atherosclerosis (12 men, 3 women) and 15 matched controls (12 men, 3 women) were analyzed using DNA microarrays. Two genes in the glutathione system Mn superoxide dismutase (P<0.05) and catalase (P<0.05) differed in expression between the groups. We conclude that macrophage uptake of oxidized LDL induces a coordinated up-regulation of genes of the glutathione and thioredoxin systems, suggesting that these systems may participate in the cellular defense against oxidized LDL and possibly modulate the development of atherosclerosis.