Lipid Oxidation Products and the Risk of Cardiovascular Diseases: Role of Lipoprotein Transport.

Cholesterol has for decades ruled the history of atherosclerotic cardiovascular diseases (CVDs), and the present view of the etiology of the disease is based on the transport of cholesterol by plasma lipoproteins. The new knowledge of the lipoprotein-specific transport of lipid oxidation products (LOPs) has introduced another direction to the research of CVD, revealing strong associations between lipoprotein transport functions, atherogenic LOP, and CVD. The aim of this review is to present the evidence of the lipoprotein-specific transport of LOP and to evaluate the potential consequences of the proposed role of the LOP transport as a risk factor.

The associations of oxidized lipoprotein lipids with lipoprotein subclass particle concentrations and their lipid compositions. The Cardiovascular Risk in Young Finns Study.

Objective: Oxidation of low-density lipoprotein (LDL) may promote atherosclerosis, whereas the reverse transport of oxidized lipids by high-density lipoprotein (HDL) may contribute to atheroprotection. To provide insights into the associations of lipoprotein lipid oxidation markers with lipoprotein subclasses at the population level, we investigated the associations of oxidized HDL lipids (oxHDL) and oxidized LDL lipids (oxLDL) with lipoprotein subclasses in a population-based cross-sectional study of 1395 Finnish adults ages 24-39 years.

Methods: The analysis of oxidized lipids was based on the determination of the baseline level of conjugated dienes in lipoprotein lipids.

The metabolic syndrome in mice overexpressing neuropeptide Y in noradrenergic neurons.

A gain-of-function polymorphism in human neuropeptide Y () gene (rs16139) associates with metabolic disorders and earlier onset of type 2 diabetes (T2D). Similarly, mice overexpressing NPY in noradrenergic neurons (OE-NPY) display obesity and impaired glucose metabolism. In this study, the metabolic syndrome-like phenotype was characterized and mechanisms of impaired hepatic fatty acid, cholesterol and glucose metabolism in pre-obese (2-month-old) and obese (4-7-month-old) OE-NPY mice were elucidated.

Oxidized lipoprotein lipids and atherosclerosis.

Plasma lipoproteins contain variable amounts of lipid oxidation products (LOP), which are known to impair normal physiological functions and stimulate atherosclerotic processes. Recent evidence indicates that plasma lipoproteins are active carriers of LOP, low-density lipoprotein (LDL) directing transport toward peripheral tissues, and high-density lipoprotein (HDL) being active in the reverse transport. It has been proposed that the lipoprotein-specific transport of LOP could play a role in atherosclerosis-related effects of LDL and HDL.

Two weeks of moderate-intensity continuous training, but not high-intensity interval training, increases insulin-stimulated intestinal glucose uptake.

Similar to muscles, the intestine is also insulin resistant in obese subjects and subjects with impaired glucose tolerance. Exercise training improves muscle insulin sensitivity, but its effects on intestinal metabolism are not known. We studied the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on intestinal glucose and free fatty acid uptake from circulation in humans.

Effect of Continuous and Intermittent Exercises on Oxidised HDL and LDL Lipids in Runners.

We studied the effects of different types of exercises on the concentrations of oxidised HDL (oxHDLlipids) and LDL lipids (oxLDLlipids), serum lipids, antioxidant potential, paraoxonase and malondialdehyde in endurance runners by performing both a 40-min continuous run (velocity corresponding to 80% VO) and a 40-min intermittent run (2-min run, velocity corresponding to 100% VO, and 2-min rest) using a treadmill. Blood samples were taken before exercise, after 20 and 40 min of exercise, and 15 and 90 min after the end of exercise. The concentrations of oxLDLlipids remained unchanged during the running tests, but after a 90-min recovery the concentrations decreased by 4% (<0.

6-mo aerobic exercise intervention enhances the lipid peroxide transport function of HDL.

During acute exercise, the concentration of oxidized high-density lipoprotein (HDL) lipids (ox-HDL) is reported to increase suggesting that HDL may function in decreasing the concentration of oxidized low-density lipoprotein (LDL) lipids. However, the effect of exercise intervention on the lipid peroxide transport function of HDL is unknown. A randomized controlled trial with sedentary women (N = 161), aged 43-63, with no current use of hormone therapy, were randomized into a 6-month (mo) exercise group and a control group.

Increased Oxidative Stress in the Proximal Stomach of Patients with Barrett's Esophagus and Adenocarcinoma of the Esophagus and Esophagogastric Junction.

Objectives: Oxidative stress (OS) is an essential element in the pathogenesis of Barrett's esophagus (BE) and its transformation to adenocarcinoma (EAC). The state of OS in the proximal stomach of patients with BE and EAC is unknown. Isoprostanes are a specific marker of OS not previously used to determine OS from BE/EAC tissue samples.

Strenuous physical exercise accelerates the lipid peroxide clearing transport by HDL.

Purpose: Physical exercise has cardioprotective functions, which have been partly linked to high-density lipoprotein (HDL), and its functions. We studied the effects of endogenous oxidative stress, induced by acute exhaustive physical exercise, on concentration of oxidized HDL lipids.

Methods: Twenty-four male national top-level endurance runners, 12 middle-distance runners and 12 marathon runners performed a maximal run on a treadmill until exhaustion.

Longitudinal study of circulating oxidized LDL and HDL and fatty liver: the Cardiovascular Risk in Young Finns Study.

Oxidative reactions are thought to play a role in the inflammatory condition called fatty liver. It is unclear whether oxidized lipoprotein lipids or proteins are associated with future fatty liver. In the Cardiovascular Risk in Young Finns Study, we determined the circulating levels of LDL and HDL oxidized lipids and studied their associations with fatty liver assessed by ultrasonography.

Co-existence of insulin resistance and high concentrations of circulating oxidized LDL lipids.

Introduction: Insulin metabolism has been previously linked to oxidized low-density lipoproteins (ox-LDL), but corroborating intervention studies are lacking. We investigated whether changes in ox-LDL levels are accompanied by changes in insulin sensitivity in a 32-month life-style intervention study.

Materials And Methods: A 2-month weight reduction was followed by 6-month diet and exercise counselling and a 2-year follow-up period.

Paraoxonase-1 and oxidized lipoprotein lipids. The Cardiovascular Risk in Young Finns Study.

Objective: Paraoxonase-1 (PON1) is suggested to have a role in the antioxidant activity of high-density lipoprotein (HDL). PON1 activity levels are strongly genetically determined by the rs662 polymorphism (PON1 Q192R). To clarify the role of PON1 in lipoprotein oxidation at the population level, we examined the relations between PON1 activity, the rs662 polymorphism and oxidized lipoprotein lipids in young adults.

Weight gain and inflammation regulate aromatase expression in male adipose tissue, as evidenced by reporter gene activity.

Obesity and white adipose tissue (WAT) inflammation are associated with enhanced aromatization in women, but little is known about the regulation of aromatase (CYP19A1) gene expression in male WAT. We investigated the impact of weight gain and WAT inflammation on the regulation of CYP19A1 in males, by utilizing the hARO-Luc aromatase reporter mouse model containing a >100-kb 5'-region of the human CYP19A1 gene. We show that hARO-Luc reporter activity is enhanced in WAT of mice with increased adiposity and inflammation.

Postprandial triglyceride response in normolipidemic, hyperlipidemic and obese subjects - the influence of polydextrose, a non-digestible carbohydrate.

Background: Three independent trials were conducted to evaluate postprandial triglyceride (TG) responses in subjects with different lipid metabolism. The effect of polydextrose (PDX), a soluble non-digestible carbohydrate, on postprandial response was also studied using practically relevant, high fat meal interventions.

Methods: A total of 19 normolipidemic (average BMI 24.

The impact of beef steak thermal processing on lipid oxidation and postprandial inflammation related responses.

Oxidised lipid species, their bioavailability and impact on inflammatory responses from cooked beef steak are poorly characterised. Oxidised lipid species from pan-fried (PF) and sous-vide (SV) thermally processed beef were determined with UHPLC-ESI/MS. Twenty-three lipid oxidation products increased with thermal processing and differences between the PF and SV steaks were measured.

High density lipoprotein level is negatively associated with the increase of oxidized low density lipoprotein lipids after a fatty meal.

Recent reports show that a fatty meal can substantially increase the concentration of oxidized lipids in low density lipoprotein (LDL). Knowing the LDL-specific antioxidant effects of high density lipoprotein (HDL), we aimed to investigate whether HDL can modify the postprandial oxidative stress after a fatty meal. Subjects of the study (n = 71) consumed a test meal (a standard hamburger meal) rich in lipid peroxides, and blood samples were taken before, 120, 240, and 360 min after the meal.

The effects of equal caloric high fat and western diet on metabolic syndrome, oxidative stress and vascular endothelial function in mice.

Aim: Nutrition contributes to increased adiposity, but it remains to be determined whether high fat rather than Western diet exacerbates the development of obesity and other characteristics of metabolic syndrome and vascular function.

Methods: We studied the effects of high fat (45% kcal) diet (HFD) and equal caloric Western diet (WD) high in fat, sucrose and cholesterol for 8 weeks in male C57B1/6N mice.

Results: Mice fed with HFD and WD showed substantially higher body adiposity (body fat %) compared with control mice receiving low fat (10%) diet (LFD).

High serum n6 fatty acid proportion is associated with lowered LDL oxidation and inflammation: the Cardiovascular Risk in Young Finns Study.

The intake of polyunsaturated fatty acids (PUFAs) is generally linked with a reduced cardiovascular disease (CVD) risk, but an elevated n6PUFA intake, without simultaneous n3PUFA supply, may elevate the risk. PUFAs are suspected as being easily oxidized and have a potential role in lipoprotein oxidation and inflammation. Saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) are resistant to oxidation.

Postpartum weight retention is associated with elevated ratio of oxidized LDL lipids to HDL-cholesterol.

Oxidized LDL lipids (ox-LDL) are associated with lifestyle diseases such as cardiovascular diseases, metabolic syndrome and type 2 diabetes. The present study investigated how postpartum weight retention effects on ox-LDL and serum lipids. The study is a nested comparative research of a cluster-randomized controlled trial, NELLI (lifestyle and counselling during pregnancy).

The associations of oxidized high-density lipoprotein lipids with risk factors for atherosclerosis: the Cardiovascular Risk in Young Finns Study.

Scavenging and reverse transport of atherogenic oxidized lipids by high-density lipoprotein (HDL) was recently suggested to contribute to atheroprotection. We investigated the associations of oxidized HDL lipids (oxHDLlipids) with known risk factors for atherosclerosis in a population-based cross-sectional study of 1395 Finnish adults ages 24-39 years (54.9% women).

α-MSH analogue attenuates blood pressure elevation in DOCA-salt hypertensive mice.

Melanocyte-stimulating hormones, α-, β- and γ-MSH, regulate important physiological functions including energy homeostasis, inflammation and sodium metabolism. Previous studies have shown that α-MSH increases sodium excretion and promotes vascular function in rodents, but it is unexplored whether these characteristics of α-MSH could translate into therapeutic benefits in the treatment of hypertension. Therefore, we first assessed the diuretic and natriuretic properties of the stable α-MSH analogue [Nle(4), D-Phe(7)]-α-MSH (NDP-α-MSH) and investigated whether it has protective effects in deoxycorticosterone acetate (DOCA)-salt hypertensive mice.

Young men with poor cardiorespiratory fitness combined with lower testosterone have high levels of oxidized LDL lipids--being fit alters this relationship.

Purpose: We hypothesized that lower androgen status together with poor physical fitness associates with atherogenic lipid profile and oxidative stress.

Methods: Volunteered young men (N = 846, mean age 25.1 ± 4.

Delay in rat lung alveolarization after the combined exposure of maternal hyperglycemia and postnatal hyperoxia.

Background: Maternal diabetes interferes with fetal lung development and postnatal treatments may further disturb pulmonary growth. Therefore, we investigated the effect of postnatal oxygen exposure on alveolar development in neonatal rat lungs pre-exposed to intrauterine hyperglycemia.

Methods: Diabetes was induced in Sprague-Dawley rats with streptozotocin injection before pregnancy.

Elevated concentration of oxidized LDL together with poor cardiorespiratory and abdominal muscle fitness predicts metabolic syndrome in young men.

Background: Metabolic syndrome (MetS) is associated with increased oxidized LDL (ox-LDL), systemic inflammation, and poor cardiorespiratory fitness. We examined affiliations of these factors and the effect of muscular fitness on MetS in young healthy men.

Methods: Physical fitness, ox-LDL, tumor necrosis factor α (TNFα), interleukin-6 (IL-6) and serum lipids were measured in a nationally representative sample of Finnish young men with and without MetS.

Genome-wide association study pinpoints a new functional apolipoprotein B variant influencing oxidized low-density lipoprotein levels but not cardiovascular events: AtheroRemo Consortium.

Background: Oxidized low-density lipoprotein may be a key factor in the development of atherosclerosis. We performed a genome-wide association study on oxidized low-density lipoprotein and tested the impact of associated single-nucleotide polymorphisms (SNPs) on the risk factors of atherosclerosis and cardiovascular events.

Methods And Results: A discovery genome-wide association study was performed on a population of young healthy white individuals (N=2080), and the SNPs associated with a P<5×10(-8) were replicated in 2 independent samples (A: N=2912; B: N=1326).