Delta-6-desaturase gene polymorphism is associated with lipoprotein oxidation in vitro.

Background: Oxidative modification of low-density lipoprotein (LDL) is a key event in the oxidation hypothesis of atherogenesis. We have previously shown that HDL does not protect LDL from oxidation in vitro, but is in fact oxidized fastest of all lipoproteins due to its rich polyunsaturated fatty acid (PUFA) composition, which is oxidation promoting. Evidence has accumulated to show that in addition to diet, common polymorphisms in the fatty acid desaturase (FADS) gene cluster have very marked effects on human PUFA status.

ADAM8 and its single nucleotide polymorphism 2662 T/G are associated with advanced atherosclerosis and fatal myocardial infarction: Tampere vascular study.

Objective: Previously, we scanned all 23,000 human genes for differential expression between normal and atherosclerotic tissues and found the involvement of ADAM8.

Methods: We investigated the expression of ADAM8 mRNA and protein level in human atherosclerotic tissues and non-atherosclerotic internal thoracic arteries as well as the association of ADAM8 2662 T/G single nucleotide polymorphism (SNP) with the extent of coronary atherosclerosis and with the risk of fatal myocardial infarction.

Results: ADAM8 mRNA was up-regulated in carotid, aortic, and femoral atherosclerotic plaques (n=24) when compared with non-atherosclerotic arteries.

Arachidonic acid increases matrix metalloproteinase 9 secretion and expression in human monocytic MonoMac 6 cells.

Background: Dietary fatty acids may modulate inflammation in macrophages of the atherosclerotic plaque, affecting its stability. The n-6 polyunsaturated fatty acid (PUFA) arachidonic acid (AA) generally promotes inflammation, while the PUFAs of the n-3 series eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) are considered anti-inflammatory. We determined how these PUFAs influence MMP-9 expression and secretion by the human monocytic cell line (MonoMac 6) at baseline and after 24-hour exposure.

Effects of oxidized low- and high-density lipoproteins on gene expression of human macrophages.

Objective: Oxidized low-density lipoprotein (ox-LDL) is a major factor in foam cell formation, whereas the role of oxidized high-density lipoprotein (ox-HDL) in this process is not known. The objective of the present study was to examine the effects of ox-LDL and ox-HDL on the gene expression of cultured human macrophages.

Material And Methods: Gene expression of human macrophages was studied after incubation for 1 day and 3 days with native and oxidized LDL and HDL using cDNA expression array.

Relation of myeloperoxidase promoter polymorphism and long-term hormone replacement therapy to oxidized low-density lipoprotein autoantibodies in postmenopausal women.

Objective: The myeloperoxidase enzyme (MPO) is a potent precursor of low-density lipoprotein (LDL) oxidation in atherosclerotic lesions. The MPO gene has a promoter polymorphism, 463G/A, which leads to high (GG) and low-expression (AG, AA) genotypes. Hormone replacement therapy (HRT) is known to affect MPO activity and LDL oxidation.