Oxidized LDL induces a coordinated up-regulation of the glutathione and thioredoxin systems in human macrophages.
Artikel i vetenskaplig tidskrift, 2006

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.

metabolism

Reverse Transcriptase Polymerase Chain Reaction

metabolism

metabolism

Thioredoxins

genetics

Female

Humans

Up-Regulation

genetics

Middle Aged

Oxidation-Reduction

Pentose Phosphate Pathway

genetics

Lipoproteins

metabolism

Male

Oligonucleotide Array Sequence Analysis

Oxidative Stress

Atherosclerosis

LDL

Macrophages

pharmacology

Glutathione

Gene Expression

Författare

Daniel Hägg

Göteborgs universitet

Mikael Englund

Göteborgs universitet

Margareta Jernås

Göteborgs universitet

Caroline Schmidt

Göteborgs universitet

Olov Wiklund

Göteborgs universitet

Lillemor Mattsson Hultén

Göteborgs universitet

Bertil Ohlsson

Göteborgs universitet

Lena M S Carlsson

Göteborgs universitet

Björn Carlsson

Göteborgs universitet

Per-Arne Svensson

Göteborgs universitet

Atherosclerosis

0021-9150 (ISSN)

Vol. 185 2 282-9

Ämneskategorier

MEDICIN OCH HÄLSOVETENSKAP

DOI

10.1016/j.atherosclerosis.2005.06.034

PubMed

16046214