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

• Published in: Atherosclerosis Vol. 185; no. 2; pp. 282 - 289
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 01.04.2006; Elsevier
• Subjects: Atherosclerosis; Atherosclerosis (general aspects, experimental research); Atherosclerosis - genetics; Atherosclerosis - metabolism; Biological and medical sciences; Blood and lymphatic vessels; Blood vessels and receptors; Cardiology. Vascular system; Female; Fundamental and applied biological sciences. Psychology; Gene Expression; genetics; Glutathione; Glutathione - genetics; Glutathione - metabolism; Glutathione and thioredoxin systems; Humans; LDL; Lipoproteins; Lipoproteins, LDL - pharmacology; Lymphatic system; Macrophage; Macrophages; Macrophages - metabolism; Male; MEDICAL AND HEALTH SCIENCES; Medical sciences; MEDICIN OCH HÄLSOVETENSKAP; metabolism; Middle Aged; Oligonucleotide Array Sequence Analysis; Oxidation-Reduction; Oxidative Stress; Oxidized LDL; Pentose Phosphate Pathway; pharmacology; Reverse Transcriptase Polymerase Chain Reaction; Thioredoxins; Thioredoxins - genetics; Thioredoxins - metabolism; Up-Regulation; Vertebrates: cardiovascular system; Oxidized LDL; Glutathione and thioredoxin systems; Macrophage; Human; Enzyme; Cardiovascular disease; Superoxide dismutase; Uptake; Defense; Vascular disease; Lipoprotein LDL; Peroxidases; Catalase; Atherosclerosis; Oxidoreductases; Reverse transcription polymerase chain reaction; Glutathione; Reductase
• ISSN: 0021-9150; 1879-1484; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2005.06.034

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.