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.

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.

Serum matrix metalloproteinase-9 and venous bypass graft occlusion.

Objective: The primary results after coronary artery bypass grafting are good, but early clinical events as a result of graft occlusion are still a problem. Early occlusions are thought to be due to thrombosis or fibrointimal hyperplasia superimposed by thrombosis, but the etiology of these phenomena is not fully understood. Matrix metalloproteinase-9 has been suggested to have a role in graft occlusion ex vivo.

HDL enhances oxidation of LDL in vitro in both men and women.

Background: Oxidative modification of low-density lipoprotein (LDL) is a key event in the oxidation hypothesis of atherogenesis. Some in vitro experiments have previously suggested that high-density lipoprotein (HDL) co-incubated with LDL prevents Cu2+-induced oxidation of LDL, while some other studies have observed an opposite effect. To comprehensively clarify the role of HDL in this context, we isolated LDL, HDL2 and HDL3 from sera of 61 free-living individuals (33 women and 28 men).

Antibody titer against malondialdehyde-modified LDL compares with HDL cholesterol concentration in identifying angiographically verified coronary artery disease. Comparison of tests by ROC analysis.

Antibody titer against malondialdehyde (MDA)-modified low-density lipoprotein (LDL) has been found to be associated with atherosclerosis, but it has not been established whether it would detect subjects with coronary artery disease (CAD). In the present study, receiver-operating characteristic (ROC) analysis was used to compare the diagnostic accuracy of the antibody titer against MDA-modified LDL and high-density lipoprotein (HDL) and LDL cholesterol levels in discrimination between subjects with (n = 51) and without (n = 35) angiographically verified 3-vessel CAD. As a result, the antibody titer against MDA-modified LDL was lower in subjects with CAD compared with subjects without CAD (p < 0.

Lipoprotein docosapentaenoic acid is associated with serum matrix metalloproteinase-9 concentration.

Background: Polyunsaturated fatty acids (PUFA) are thought to play important roles in inflammation. The n-3 series is considered as anti-inflammatory, and some studies have reported increased plasma n-3 polyunsaturated fatty acid pattern in chronic inflammatory conditions. In this study we sought to clarify relationships of the levels of arachidonic acid and the polyunsaturated n-3 fatty acid compositions of isolated LDL, HDL2 and HDL3 particles with matrix metalloproteinase-9 (MMP-9), a marker of inflammation.

Serum matrix metalloproteinase-9 is elevated in men with a history of myocardial infarction.

Elevated serum inflammatory markers have been reported in coronary heart disease. Levels of serum matrix metalloproteinase-9 (MMP-9), C-reactive protein (CRP), C3-complement (C3) and autoantibodies against oxidized low-density lipoprotein (oxLDL) in 120 male subjects with a history of myocardial infarction (MI) were compared with those in 250 age-matched controls, both groups from a large cross-sectional population survey, the FINRISK study. The concentrations of serum MMP-9 and autoantibodies against oxLDL were measured by enzyme-linked immunosorbent assay, CRP and C3 by immunonephelometry.

Alcohol misuse increases serum antibodies to oxidized LDL and C-reactive protein.

Aims: To clarify the relationship of alcohol consumption with serum antibodies to oxidized low-density lipoprotein (oxLDL) and the inflammation marker C-reactive protein (CRP).

Methods: The study population consisted of 280 men with evidence of alcohol misuse by having self-reported alcohol consumption values over 280 g absolute ethanol per week and 250 age-matched moderate drinkers from a population of Finnish men participating in the FINRISK survey study. Serum samples were analysed for antibodies to oxLDL, C-reactive protein (CRP), total cholesterol, HDL-cholesterol, triglycerides, carbohydrate-deficient transferrin (CDT) and gamma-glutamyl transferase (GGT).

Myeloperoxidase gene variation and coronary flow reserve in young healthy men.

Chronic inflammation may lead to endothelial dysfunction, which manifests as an impaired coronary reactivity. Impairment in coronary flow reserve (CFR), preceding the clinical symptoms of coronary artery disease, can be measured noninvasively by positron emission tomography. Myeloperoxidase (MPO) is an oxidative enzyme present in phagocytes and atherosclerotic lesions.

Oxidized LDL autoantibodies are related to apolipoprotein E phenotype, independently of postprandial change in plasma triglycerides and LDL size, among patients with angiographically verified coronary artery disease and healthy controls.

Objective: Oxidized low-density lipoprotein (LDL) autoantibodies (oxLDLab), apolipoprotein E (apoE) phenotype, postprandial triglyceride changes and LDL size are suggested to be risk factors for coronary artery disease (CAD). Our aim was to study the interaction between these new risk factors among patients with CAD and healthy controls.

Methods: oxLDLab from 31 men with angiographically verified CAD and 31 healthy men were analyzed by enzyme-linked immunosorbent assay.

Suppression of viability and acetyl-LDL metabolism in RAW 264 macrophage-like and smooth muscle cells by bisphosphonates in vitro.

Etidronate and clodronate are bisphosphonates that inhibit the development of experimental atherosclerosis. Etidronate decreases the intimamedia thickness of carotid artery even in man. Liposome-encapsulated bisphosphonates inhibit the cellular metabolism of atherogenic, modified low-density lipoprotein (acetyl-LDL) by cultured macrophages.

High oxidized LDL and elevated plasma homocysteine contribute to the early reduction of myocardial flow reserve in healthy adults.

Background: Impairment of coronary blood flow reserve has been shown to be an early manifestation of atherosclerosis and coronary artery disease (CAD). We studied more closely the contribution of various risk factors on early deterioration of coronary function.

Materials And Methods: Fifty-one young, apparently healthy adults, with normal or mildly elevated serum cholesterol levels but without other major risk factors for CAD, such as diabetes or hypertension, underwent positron emission tomography (PET) studies.

Oestrogen receptor gene variation is a determinant of coronary reactivity in healthy young men.

Background: Oxidised low-density lipoprotein (ox-LDL) is a determinant of impaired coronary function and oestrogens inhibit its formation probably throughout genetically-variable oestrogen receptor 1 (ESR1) in artery wall. We hypothesized that the ESR1 polymorphism might influence coronary function and reactivity as measured by positron emission tomography (PET), which allows the detection of coronary dysfunction before appearance of angiographic lesions.

Materials And Methods: Fifty-one healthy young men (aged 35 +/- 4 years), with normal or slightly-elevated serum cholesterol, underwent PET with intravenous adenosine.

Association of serum MMP-9 with autoantibodies against oxidized LDL.

Monocyte-derived macrophages in atherosclerotic plaques secrete matrix metalloproteinases (MMPs), which may contribute to plaque rupture. There has been much speculation as to which factors precipitate in the arterial inflammation. Oxidized low density lipoprotein (oxLDL) has been suggested to have proinflammatory properties, and it has been shown to increase matrix metalloproteinase-9 (MMP-9) secretion by macrophages in vitro.

Paraoxonase gene polymorphisms and coronary reactivity in young healthy men.

This study examined the relationships between paraoxonase genotypes, coronary artery reactivity, and indices of low-density lipoprotein oxidation in healthy men. Impairment in coronary flow reserve, as assessed by positron emission tomography, is associated with lipoprotein oxidation, which is affected by high-density lipoprotein bound enzyme, paraoxonase. Paraoxonase has two common polymorphisms (M/L55 and R/Q192) that change the activity of the enzyme.

The relation of oxidized LDL autoantibodies and long-term hormone replacement therapy to ultrasonographically assessed atherosclerotic plaque quantity and severity in postmenopausal women.

Background: In epidemiologic studies, the incidence of atherosclerosis rises soon after menopause in women, and hormone replacement therapy (HRT) has proved to be useful in preventing onset of clinical manifestations of the disease. However, it is not known how HRT affects sonographically determined atherosclerotic severity (AS) and number of atherosclerotic plaques (NAP) in large arteries. Furthermore, it is not clear how HRT affects oxidation of low density lipoproteins (LDL), which obviously has an important role in the pathogenesis of atherosclerosis.

Autoimmune responses against oxidant stress and acetaldehyde-derived epitopes in human alcohol consumers.

Background: Studies in experimental animals have indicated that chronic ethanol ingestion triggers the formation of antibodies directed against proteins modified with reactive metabolites of ethanol and products of lipid peroxidation. However, the nature and prevalence of such antibodies have not been compared previously in alcoholic patients.

Methods: Autoantibodies against adducts with acetaldehyde- (AA), malondialdehyde- (MDA), and oxidized epitopes (Ox) were examined from sera of 54 alcohol consumers with (n = 28) or without (n = 26) liver disease, and from 20 nondrinking controls.

Autoantibodies against oxidised low-density lipoprotein in patients with obstructive sleep apnoea.

Autoantibodies against oxidised low-density lipoprotein (OxLDL-Abs) have been proposed to be an indicator of endothelial dysfunction and a novel tool for finding individuals with a high cardiovascular risk. In a cross-sectional study, OxLDL-Abs were measured in 297 patients with obstructive sleep apnoea (OSA) and 54 controls using an enzyme-linked immunosorbent assay. The autoantibodies were increased in patients with OSA when compared to controls (age, body mass index (BMI) and gender adjusted, p = 0.

Metabolism of modified LDL and foam cell formation in murine macrophage-like RAW 264 cells.

The uptake of modified low density lipoprotein (LDL) by arterial macrophages is a key event in the atherogenesis. We studied 1) the uptake and degradation of modified LDL, 2) LDL recognition by specific receptors, and 3) the foam cell formation with murine macrophage-like RAW 264 cells in vitro. The cells took up and degraded effectively 125I-labeled acetylated LDL (Ac-LDL) and aggregated LDL (Aggr-LDL).

Autoantibodies against oxidized low density lipoprotein in patients with angiographically verified coronary artery disease.

Oxidation of low density lipoproteins (LDL) obviously plays an important role in the pathogenesis of atherosclerosis. The purpose of the study was to determine whether antibodies against oxidized LDL are associated with coronary artery disease (CAD). We determined the serum levels of antibodies against copper-oxidized LDL by enzyme-linked immunosorbent assay in 58 patients with angiographically verified CAD and 34 controls without CAD.