Susceptibility Of Lipoprotein Research Articles

Impact of Lipids and Vascular Damage on Early Atherosclerosis in Adolescents with Parental Premature Coronary Artery Disease.

To assess the relationship of cardiovascular risk factors (CRFs) with carotid intima media thickness (IMT) in adolescents with a parental history of premature coronary artery disease (PCAD). This cross-sectional study included 50 healthy adolescents, aged 14-18years, both sexes, with a parental history of PCAD, that were compared to 50 controls without this history. Questionnaires regarding information of CRFs were applied. Blood chemistry analyses, included lipid profile, lipoprotein (a), low density lipoprotein (LDL) susceptibility to oxidation, and inflammatory cytokine levels. The IMT was evaluated by ultrasound. The mean age of all participants was 15.9years. Anthropometric measurements, blood pressure, and lipid profile were similar in both groups. However, the parental history of PCAD group exhibited lower high density lipoprotein cholesterol concentrations, shorter LDL particle oxidation time, and higher lipoprotein (a) levels compared to the control group. IMT was significantly higher in adolescents with a parental history of PCAD compared to controls, (0.53±0.04mm vs 0.47±0.02mm, p=0.001). Among adolescents with a parental history of PCAD, those with ≥3 CRFs had significantly higher IMT values (0.56mm) than those with <3 CRFs (0.52mm) and controls (0.48mm). Multivariable analyses identified that systolic blood pressure and parental history of PCAD explained 26.8% and 16.1% of the variation in IMT. Furthermore, body mass index, LDL-C, ApoB-100, triglycerides and lipoprotein (a) interact with blood pressure levels to explain the IMT values. Adolescents with a parental history of PCAD had higher IMT values than the control group, primary explained by systolic blood pressure and the parental inheritance. Adolescents with parental history of PCAD and ≥3 CRFs exhibited the highest IMT values. Notably, lipids and systolic blood pressure jointly contribute to explain IMT in these adolescents.

Protective effects of paraoxonase-1, vitamin E and selenium, and oxidative stress index on the susceptibility of low density lipoprotein to oxidation in diabetic patients with/without coronary artery disease

BackgroundThe oxidative modification of low density lipoprotein (LDL) is closely associated with an increased risk for coronary artery disease (CAD) in diabetic patients. The purpose of this study is to investigate the relation between serum vitamin E and selenium, paraoxonase-1 (PON1) activity, total antioxidant capacity (TAC), total oxidant status (TOS), malondialdehyde (MDA), and oxidative stress index (OSI) values with the susceptibility of LDL to oxidative modification and the possibility of CAD in diabetic patients.MethodThis study was designed as a case control survey of 82 diabetes patients divided into two groups including T2DM alone (as group I) and both T2DM and CAD (as group II). Fasting blood samples were taken to the assay of fasting blood glucose (FBG), HbA1c, total cholesterol (TC), TAC, TOS, MDA, OSI, vitamin E, selenium, oxidized low density lipoprotein (Ox-LDL), and activity of PON1.ResultsOx-LDL, MDA, TOS, and OSI values in groups II were significantly higher compared with group I (all with P value = 0.000). TAC, vitamin E, selenium, and PON1 activity values were significantly lower in group II compared with groups I (P value = 0.000; P value = 0.000; P value = 0.007; P value = 0.003, respectively). There were significant relationships between the amounts of TAC, TOS, OSI, and vitamin E with the amounts of PON1 activity and Ox-LDL (p < 0.05). But Ox-LDL and PON1 activity correlated weakly with together (p = 0.094).ConclusionResults of this study support the belief that oxidative stress might be an important etiologic factor which makes some diabetics more susceptible to CAD. Increased oxidative stress may be a potential therapeutic target in the prevention and management of CAD in diabetic patients.

Dysfunctional antioxidant capacity of high-density lipoprotein in rheumatoid arthritis.

High-density lipoprotein (HDL) presents atheroprotective functions not readily reflected by plasma HDL-cholesterol levels. The aim of this study was to investigate HDL antioxidant function in patients with rheumatoid arthritis (RA). This pilot and cross-sectional study included 50 RA patients and 50 controls matched by age, gender, cardiovascular risk factors and drug therapy. The antioxidant capacity of HDL was assessed by the total radical-trapping antioxidative potential test (TRAP-assay) and the susceptibility of low-density lipoprotein (LDL) to oxidation by the Conjugated Dienes Assay (Dmax ). A carotid ultrasound was performed in all participants to detect subclinical atherosclerosis. High-density lipoprotein from RA patients showed lower antioxidant capacity than those from controls [oxidized-LDL%: 35.8 (27-42) vs. 24.4 (20-32), p < .001] when analysed with the TRAP-assay. In addition, the time to achieve 50% of maximal LDL oxidation (Lag-time) was shorter in RA-patients than in matched controls [57.2 (42-71) vs. 69.5 (55-75) minutes, (p = .003)]. RA patients showed a higher atherosclerotic burden than controls. The pro-oxidant pattern in RA was irrespective of the presence of carotid atherosclerosis. On the contrary, there was a positive correlation between inflammatory parameters (erythrocyte sedimentation rate, ultrasensitive C-reactive protein and fibrinogen) and the loss of HDL-anti-oxidant capacity measured by the TRAP-assay (rho = .211, p = .035; rho = .231, p = .021 and rho = .206, p = .041, respectively). Furthermore, the glucocorticoid dose at recruitment was negatively associated with the Lag-time in RA patients (rho = -.387, p = .026). Rheumatoid arthritis patients present reduced HDL antioxidant capacity and a lower resistance of LDL particles to oxidation, mainly related to the degree of inflammation.

Copper Deficiency Increases the Susceptibility of Lipoproteins and Tissues to Peroxidation in Rats

Male Wistar rats were pair-fed from weaning for 6 wk either a copper-deficient diet or a control diet containing sucrose. Hypercholesterolemia in copper-deficient animals was associated with a significantly greater plasma apolipoprotein B concentration and modifications in the lipid composition of triglyceride-rich lipoproteins containing apolipoprotein B. The proportion of triglycerides was elevated and the proportion of cholesterol was reduced in the VLDL + LDL fractions from copper-deficient rats compared with control animals. When the VLDL + LDL fractions were subjected to in vitro copper-induced oxidation, the lipoprotein fractions from copper-deficient rats were more susceptible to oxidative damage than lipoprotein fractions from control rats as indicated by the rate of diene conjugation. Hydroperoxide and thiobarbituric acid-reactive substance (TBARS) measurements performed 3 h after the induction of peroxidation were in agreement with the greater formation of conjugated dienes. Concentrations of TBARS were significantly greater in heart homogenates from copper-deficient rats compared with control rats. After exposure of tissue homogenates to iron-induced lipid peroxidation, TBARS were significantly higher in liver and heart from copper-deficient rats compared with control rats. Of particular importance is the observation that copper deficiency has a harmful effect on lipid peroxidation in the cardiovascular system.

The human liver lipidome is significantly related to the lipid composition and aggregation susceptibility of low-density lipoprotein (LDL) particles

Background and aimsThe susceptibility of low-density lipoprotein (LDL) to aggregation predicts atherosclerotic cardiovascular disease. However, causes of interindividual variation in LDL lipid composition and aggregation susceptibility remain unclear. We examined whether the lipid composition and aggregation susceptibility of LDL reflect the lipid composition of the human liver. MethodsLiver biopsies and blood samples for isolation of LDL particles were obtained from 40 obese subjects (BMI 45.9 ± 6.1 kg/m2, age 43 ± 8 years). LDL was isolated using sequential ultracentrifugation and lipidomic analyses of liver and LDL samples were determined using ultra-high performance liquid chromatography–mass spectrometry. LDL aggregation susceptibility ex vivo was analyzed by inducing aggregation by human recombinant secretory sphingomyelinase and following aggregate formation. ResultsThe composition (acyl carbon number and double bond count) of hepatic triglycerides, phosphatidylcholines, and sphingomyelins (SMs) was closely associated with that of LDL particles. Hepatic dihydroceramides and ceramides were positively correlated with concentrations of the corresponding SM species in LDL as well with LDL aggregation. These relationships remained statistically significant after adjustment for age, sex, and body mass index. ConclusionsLipid composition of LDL reflects that of the human liver in obese patients. Changes in hepatic sphingolipid metabolism may contribute to interindividual variation of LDL lipid composition and susceptibility to aggregation.

Comparative Susceptibility to Oxidation of Different Classes of Blood Plasma Lipoproteins.

The kinetics of free radical peroxidation of different classes of blood plasma lipoproteins (nanoparticles involved in lipid transport in the body) was studied. The susceptibility of atherogenic low-density lipoproteins (LDLs) to the Cu2+-initiated free radical peroxidation in vitro was found to be more than ten times higher than that of antiatherogenic high density lipoproteins (HDLs). The baseline content of acyl hydroperoxy derivatives of phospholipids (primary products of free radical peroxidation) in the outer layer of LDL particles in vivo measured per particle exceeded the baseline content of these compounds in HDL particles by more than an order of magnitude. The susceptibility to oxidation of the HDL2 subfraction of HDLs was higher than the susceptibility of total HDL fraction and HDL3 subfraction. The data obtained confirm an important role of free radical peroxidation of LDLs in the molecular mechanisms of vascular wall damage in atherosclerosis.

Kinetics of lipid radical formation in lipoproteins from β-thalassemia: Implication of cholesteryl esters and α-tocopherol

Vascular complications in β-thalassemia are associated with oxidative modification of lipoproteins under high oxidative stress. The lipid components of lipoproteins are oxidized via lipid peroxidation and produce lipid radicals (L•) as the key initial intermediates. Modification of lipid components, therefore, might result in alterations in the rate and products of lipid peroxidation. In this study, the kinetics of L• formation during the 2,2'-Azobis(2-amidinopropane) dihydrochloride (AAPH)- and hemin-induced oxidation of low-density and high-density lipoproteins (LDL and HDL) from β-thalassemia patients and healthy volunteers were investigated using a specific and sensitive fluorescence probe for L•. Kinetic parameters, including initial lag time, propagation rate and total L• production, were calculated by monitoring a fluorescence-active NBD-Pen-L• adduct. Oxidation of thalassemia lipoproteins exhibited a significantly shorter lag time but a slower propagation rate of L• formation when compared with healthy lipoproteins. LDL showed higher resistance to oxidation during the initiation phase but higher L• formation than HDL. Our results indicated that the levels of α-tocopherol determined the initial lag time, whereas the levels of core lipids and cholesteryl esters, especially cholesteryl linoleate (CL), determined the propagation rate and total L• production. The difference in potency of AAPH and hemin supported that hemin preferentially targeted core lipids. Moreover, analysis of 13-hydroxyoctadecadienoic acid cholesteryl ester (13-HODE-CE)/CE ratio indicated that thalassemia lipoproteins have higher susceptibility to oxidation than healthy lipoproteins. In conclusion, our findings suggested that CL and α-tocopherol were implicated in the susceptibility of lipoproteins to lipid peroxidation in physiological and pathological conditions of β-thalassemia.

Aggregation Susceptibility of Low-Density Lipoproteins-A Novel Modifiable Biomarker of Cardiovascular Risk.

Circulating low-density lipoprotein (LDL) particles enter the arterial intima where they bind to the extracellular matrix and become modified by lipases, proteases, and oxidizing enzymes and agents. The modified LDL particles aggregate and fuse into larger matrix-bound lipid droplets and, upon generation of unesterified cholesterol, cholesterol crystals are also formed. Uptake of the aggregated/fused particles and cholesterol crystals by macrophages and smooth muscle cells induces their inflammatory activation and conversion into foam cells. In this review, we summarize the causes and consequences of LDL aggregation and describe the development and applications of an assay capable of determining the susceptibility of isolated LDL particles to aggregate when exposed to human recombinant sphingomyelinase enzyme ex vivo. Significant person-to-person differences in the aggregation susceptibility of LDL particles were observed, and such individual differences largely depended on particle lipid composition. The presence of aggregation-prone LDL in the circulation predicted future cardiovascular events in patients with atherosclerotic cardiovascular disease. We also discuss means capable of reducing LDL particles’ aggregation susceptibility that could potentially inhibit LDL aggregation in the arterial wall. Whether reductions in LDL aggregation susceptibility are associated with attenuated atherogenesis and a reduced risk of atherosclerotic cardiovascular diseases remains to be studied.

Proteoglycan binding as proatherogenic function metric of apoB-containing lipoproteins and chronic kidney graft failure

Lipoprotein-proteoglycan binding is an early key event in atherosclerotic lesion formation and thus conceivably could play a major role in vasculopathy-driven chronic graft failure and cardiovascular mortality in renal transplant recipients. The present study investigated whether lipoprotein-proteoglycan binding susceptibility (LPBS) of apoB-containing lipoproteins and levels of the classical atherosclerosis biomarker LDL-C were associated with cardiovascular mortality (n = 130) and graft failure (n = 73) in 589 renal transplant recipients who were followed up from at least 1 year after transplantation for 9.5 years. At baseline, LPBS was significantly higher in patients who subsequently developed graft failure than in those with a surviving graft (1.68 ± 0.93 vs. 1.46 ± 0.49 nmol/mmol, P = 0.001). Cox regression analysis showed an association between LPBS and chronic graft failure in an age- and sex-adjusted model (hazard ratio: 1.45; 95% CI, 1.14–1.85; P = 0.002), but no association was observed with cardiovascular mortality. LDL-C levels were not associated with graft failure or cardiovascular mortality. This study shows that measurement of cholesterol retention outperformed the traditionally used quantitative parameter of LDL-C levels in predicting graft failure, suggesting a higher relevance of proatherogenic function than the quantity of apoB-containing lipoproteins in chronic kidney graft failure.

Synergistic Efficacy of Aframomum Melegueta [Roscoe] K. Schum and Spondias mombin (Linn), a Predictive Treatment of SARS-CoV-2 (COVID-19) Infection

SARS-CoV-2 is closely related to the original SARS-CoV. It is thought to have animal based origin from Bats(Betacoronavirus) in subgenus (Sarbecoronavirus) together with two bat-derived strains The virus is mainly spread between people during physical contact, often through small droplets produced during coughing, sneezing, even talking to patient or infected people. It is primarily spread during close contact and via small droplets produced when infected people cough, sneeze or talk with close contact being within 1–3 m (3 ft 3 in–9 ft 10 in). Those infected with the virus may be asymptomatic (Appearance of No symptoms) or develop flu-like symptom which include fever, cough, fatigue, and shortness of breath. The exposure time to initial symptom is day five (5 days). Majority of cases result in mild symptoms, some progress to viral pneumonia and multiple organ failure. Two medicinal plants may be used for the treatment of SARS-CoV-2, the two medicinal plants are Aframomum melegueta and Spondis mombin (Linn). Both contains arrays of natural product that may be used for drug formulation to combat SARS-CoV-2, Aframomum melegueta medicinal plant belong to the family Zingiberaceae which can be used to detoxify liver and bronchitis during lungs infection. Aframomum melegueta contains 6-Gingerol, 8-Gingerol, Methyl-6-Gingerol, 6-Shogaol, 6-Rac-6-Dihydro paradol,6-Gingeredione, 2-(5 butylfuran-2-yl) ethyl}-2-methoxyphenol and 6-Paradol. Secondary metabolite(Phytochemical)investigations of Aframomum melegueta extracts revealed the presence of (-)-buplerol, (-)-arctigenin, (E)- 14-hydroxy-15-norlabda-8(17), 12-dien- 16-al, labda-8(17), 12-dien-15, 16- dial, 16-oxo-8(17), 12(E)-labdadien-15-oic acid, 5-hydroxy-7-methoxy flavone and apigenin, The combination of all this novel compound can be used for the treatment of SARS-CoV-2. Spondias mombin belongs to the family of Anacardiaceae medicinal plants and contains Catechin and Epigalocatechin, Epicatechin, Stigmasterol and Phytosterol, a very important flavonoid that can be used in drug formulation because of its extensive therapeutic properties which may inhibit specific enzymes, blocking the angiotensin-converting enzyme (ACE) that raises blood pressure of infected patient during elevated fever clinical symptoms of SARS-CoV-2 (COVID-19). Spondias monbin extract may act by blocking the “suicide” enzyme cyclooxygenase that breaks down prostaglandins, they also prevent platelet aggregation. Cancer-battling antioxidants, flavonoids, have been found in relative abundance in Aframomum melegueta and Spondias mombin. Epicatechin have been proven to have diverse benefits to human health. It reduces the risks of diabetes mellitus and cardiovascular diseases, EGC acts as a strong inhibitor of HIV replication in cultured peripheral blood cells and inhibition of HIV-1 reverse transcriptase in vitro. EGC binds directly to CD4 molecules with consequent inhibition of Gp 120 binding and inactivate viruses in vitro by deformation of phospholipids, Epicatechin and other polyphenols decreases the susceptibility of low density lipoprotein to oxidation which prevents the initiation of artherosclerosis, HIV protein (Tat) and gp120.In conclusion. SARS-CoV-2(COVID-19) pandemic infection should not be a death sentence, it should be an advancement into the scientific world especially the naturally occurring product that can be used in the formulation of new antimicrobial agents.

Antioxidant and Pro-Oxidant Properties of Carthamus Tinctorius, Hydroxy Safflor Yellow A, and Safflor Yellow A.

(1) Carthamus Tinctorius L. (safflower) is extensively used in traditional herbal medicine. (2) The aim of this study was to investigate the bioactive properties of polyphenol extracts from flowers of Carthamus Tinctorius (CT) cultivated in Italy. We also evaluated the properties of two bioactive water-soluble flavonoid compounds, hydroxy safflor yellow A (HSYA) and safflor yellow A (SYA), contained in Carthamus Tinctorius petals. (3) The total polyphenol content was 3.5 ± 0.2 g gallic acid equivalent (GAE)/100 g, flavonoids content was 330 ± 23 mg catechin equivalent (CE)/100 g in the flowers. The extract showed a high antioxidant activity evaluated by oxygen radical absorbance capacity (ORAC) and 2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging assays. In addition, flower extract, SYA, and HSYA were able to reduce the susceptibility of low-density lipoprotein to copper-induced lipid peroxidation. In order to investigate the bioactive properties of flower extract, SYA, and HSYA we also studied their modulatory effect of oxidative stress on human dermal fibroblasts (HuDe) oxidized by tert-butyl hydroperoxide (t-BOOH). The CT extract at concentrations ranging from 0.01–20 μg GAE/mL of polyphenols, exerted a protective effect against t-BOOH triggered oxidative stress. At higher concentration the extract exerted a pro-oxidant effect. Similar results have been obtained using HSYA and SYA. (4) These results demonstrate a biphasic effect exerted by HSYA, SYA, and flower extracts on oxidative stress.

Effects of triacylglycerol on the structural remodeling of human plasma very low- and low-density lipoproteins

Very low-density lipoprotein (VLDL) is the main plasma carrier of triacylglycerol that is elevated in pathological conditions such as diabetes, metabolic syndrome, obesity and dyslipidemia. How variations in triacylglycerol levels influence structural stability and remodeling of VLDL and its metabolic product, low-density lipoproteins (LDL), is unknown. We applied a biochemical and biophysical approach using lipoprotein remodeling by lipoprotein lipase and cholesterol ester transfer protein, along with thermal denaturation that mimics key aspects of lipoprotein remodeling in vivo. The results revealed that increasing the triacylglycerol content in VLDL promotes changes in the lipoprotein size and release of the exchangeable apolipoproteins. Similarly, increased triacylglycerol content in LDL promotes lipoprotein remodeling and fusion. These effects were observed in single-donor lipoproteins from healthy subjects enriched in exogenous triolein, in single-donor lipoproteins from healthy subjects with naturally occurring differences in endogenous triacylglycerol, and in LDL and VLDL from pooled plasma of diabetic and normolipidemic patients. Consequently, triacylglycerol-induced destabilization is a general property of plasma lipoproteins. This destabilization reflects a direct effect of triacylglycerol on lipoproteins. Moreover, we show that TG can act indirectly by increasing lipoprotein susceptibility to oxidation and lipolysis and thereby promoting the generation of free fatty acids that augment fusion. These in vitro findings are relevant to lipoprotein remodeling and fusion in vivo. In fact, fusion of LDL and VLDL enhances their retention in the arterial wall and, according to the response-to-retention hypothesis, triggers atherosclerosis. Therefore, enhanced fusion of triacylglycerol-rich lipoproteins suggests a new causative link between elevated plasma triacylglycerol and atherosclerosis.

Increased Cardiac Sympathetic Activity and Oxidative Stress in Habitual Electronic Cigarette Users

Electronic cigarettes (e-cigarettes) have gained unprecedented popularity, but virtually nothing is known about their cardiovascular risks. To test the hypothesis that an imbalance of cardiac autonomic tone and increased systemic oxidative stress and inflammation are detectable in otherwise healthy humans who habitually use e-cigarettes. Cross-sectional case-control study of habitual e-cigarette users and nonuser control individuals from 2015 to 2016 at the University of California, Los Angeles. Otherwise healthy habitual e-cigarette users between the ages of 21 and 45 years meeting study criteria, including no current tobacco cigarette smoking and no known health problems or prescription medications, were eligible for enrollment. Healthy volunteers meeting these inclusion criteria who were not e-cigarette users were eligible to be enrolled as control individuals. A total of 42 participants meeting these criteria were enrolled in the study including 23 self-identified habitual e-cigarette users and 19 self-identified non-tobacco cigarette, non-e-cigarette user control participants. Heart rate variability components were analyzed for the high-frequency component (0.15-0.4 Hz), an indicator of vagal activity, the low-frequency component (0.04-0.15 Hz), a mixture of both vagal and sympathetic activity, and the ratio of the low frequency to high frequency, reflecting the cardiac sympathovagal balance. Three parameters of oxidative stress were measured in plasma: (1) low-density lipoprotein oxidizability, (2) high-density lipoprotein antioxidant/anti-inflammatory capacity, and (3) paraoxonase-1 activity. Of the 42 participants, 35% were women, 35% were white, and the mean age was 27.6 years. The high-frequency component was significantly decreased in the e-cigarette users compared with nonuser control participants (mean [SEM], 46.5 [3.7] nu vs 57.8 [3.6] nu; P = .04). The low-frequency component (mean [SEM], 52.7 [4.0] nu vs 39.9 [3.8] nu; P = .03) and the low frequency to high frequency ratio (mean [SEM], 1.37 [0.19] vs 0.85 [0.18]; P = .05) were significantly increased in the e-cigarette users compared with nonuser control participants, consistent with sympathetic predominance. Low-density lipoprotein oxidizability, indicative of the susceptibility of apolipoprotein B-containing lipoproteins to oxidation, was significantly increased in e-cigarette users compared with nonuser control individuals (mean [SEM], 3801.0 [415.7] U vs 2413.3 [325.0] U; P = .01) consistent with increased oxidative stress, but differences in high-density antioxidant/anti-inflammatory capacity and paraoxonase-1 activity were not significant. In this study, habitual e-cigarette use was associated with a shift in cardiac autonomic balance toward sympathetic predominance and increased oxidative stress, both associated with increased cardiovascular risk.

Association of socioeconomic stratification with plasmatic markers of lipoperoxidation and antioxidants in Venezuelan school-age children

To establish association between socioeconomic status and plasmatic markers of lipoperoxidation and antioxidants in Venezuelan school-age children from the middle-class and in critical poverty. Cross-sectional study with a sample of 114 school-age children (aged 7-9). The socioeconomic status, dietary intake of macro and micro-nutrients, weight, height, lipid profile, indicators of lipid peroxidation and enzymatic and non-enzymatic antioxidants were determined. The daily average intake of energy, carbohydrates and vitamin A, and the percentage of energy obtained from carbohydrates was significantly higher in middle-class children compared to critical poverty children (p <0.05). The circulating oxidized low density lipoprotein (p <0.001) and the susceptibility of low density lipoproteins and very low density lipoproteins to oxidation in vitro (p <0.05) were significantly higher in middle-class children, while the critical poverty children showed significantly lower levels of Vitamin C and E in plasma (p <0.05). Non-enzymatic antioxidant levels were frequently deficient in both strata. The concentrations of circulating oxidized low density lipoprotein (OR: 1.09, CI 95%: 1.016-1.179; p= 0.017) and Vitamin C (OR: 3.21, CI 95%: 1.104-9.938; p= 0.032) were associated to the socioeconomic status independently of gender, family history of premature coronary artery disease, triglicerides, Vitamin C and E dietary intake and count of white blood cells. The socioeconomic status was associated to circulating oxidized low density lipoprotein and Vitamin C in Venezuelan school-age children, The results suggested the need to improve the dietary intake of antioxidants in both studied socioeconomic groups.

Adiponectin: possible link between metabolic stress and oxidative stress in the elderly.

The aim of this study was to evaluate the relationships between the serum levels of adiponectin and systemic oxidative stress exerted on lipids, proteins, as well as endothelial function and cardiovascular diseases (CVD) risk markers, in elderly subjects with metabolic syndrome (MS). The serum advanced glycation and oxidation protein products, low-density lipoprotein susceptibility to oxidation (oxLDL), nitric oxide metabolic pathway products (NOx), serum lipid peroxidation, as well as total antioxidant/oxidative capacity (TAC/TOC), were analyzed in elderly subjects with MS (n=44), compared to aged-matched control (n=39). We pointed out significantly lower levels of adiponectin in elderly MS subjects concomitantly with significantly higher levels of oxidative stress and CVD risk markers. Significant positive correlations were found between serum adiponectin levels and HDL-cholesterol (p<0.05) and the total cholesterol/LDL-cholesterol ratio (p<0.01). Additionally, adiponectin levels were significantly inversely associated with insulin resistance index (HOMA-IR, r=-0.348; p<0.05) and serum lipid peroxidation (r=-0.337; p<0.05), and significantly positively with the antioxidant capacity (TAC, r=0.339; p<0.05). Conversely, adiponectin levels were significantly negatively (r=-0.310; p<0.05) associated with serum uric acid concentration. The major protective role of adiponectin versus stress related to an impaired glucose and lipid metabolism suggests that adiponectin plays a critical role in adiposity-related metabolic stress and redox homeostasis.

Relationship between selected oxidative stress markers and lipid risk factors for cardiovascular disease in middle-aged adults and its possible clinical relevance

ObjectivesDecreased activity of HDL-associated paraoxonase 1 (PON1) and elevated levels of lipid peroxides together with abnormal lipid profile may prognosticate the progression of atherosclerosis. The aim of this study was to assess associations between selected oxidative stress markers (PON1, lipid peroxides) and lipid risk factors for cardiovascular disease in middle-aged subjects. Design and methodsArylesterase activity of PON1; lipid peroxides; total-, HDL-, LDL-, non-HDL-cholesterol; triglycerides; apolipoproteins A-I (ApoA-I) and B (ApoB), and lipid risk indexes were determined in serum of 75 volunteers (mean age 41.7±8.2years). Forty six volunteers were divided into normolipidemic (NL) and hyperlipidemic (HL) group. ResultsElevated levels of atherogenic cholesterol (LDL, non-HDL), lipid risk indexes (p<0.0001), lipid peroxides (p<0.001), and decreased activity of PON1 (p<0.05) were found in HL group. Strong correlations between PON1 activity and HDL (r=0.635, p=0.0005), apolipoprotein A-I (r=0.703, p<0.0001), ApoA-I/ApoB ratio (r=0.536, p=0.004), and non-HDL/HDL ratio (r=−0.445, p=0.013) were observed in NL group. There was no significant association between PON1 activity and these parameters in HL group. ConclusionsSignificant abnormalities of lipid parameters, oxidative stress markers and associations between PON1, HDL and apolipoprotein A-I may influence the antioxidant and anti-atherogenic functions of HDL and result in the higher susceptibility of lipoproteins to oxidative modification. Monitoring of lipid profile together with oxidative stress markers in an asymptomatic population could be beneficial for early identification of atherosclerosis-related diseases.

Lipoprotein subfraction oxidation in acute exercise and ageing

ABSTRACTExercise and ageing can independently increase free radical production that may enhance the susceptibility of LDL to oxidation and create a more atherogenic LDL particle. This investigation was designed to examine exercise and ageing on the susceptibility of LDL subfractions to oxidation. Eleven aged (55 ± 4 years) and twelve young (21 ± 2 years) participants completed a progressive exercise test to exhaustion and within one week performed a 1 h bout of moderate intensity (65% VO2max) exercise. Blood was assayed for metabolites associated with lipid composition (total cholesterol, free cholesterol, triglycerides) and lipoprotein susceptibility to oxidation. Exercise increased small density (sdLDL) oxidation, independently of age (p < 0.05). However, sdLDL oxidation further increased 24 h post exercise in the aged group (p < 0.05). With regards to the changes in lipid components within LDL, free and total cholesterol and triglycerides in large buoyant (lbLDL) were all elevated 24 h post exercise in aged compared with young (p < 0.05 for all comparisons). There was a decrease in triglycerides in medium density (mdLDL) 24 h post exercise in the aged group (p < 0.05). The lipid composition of sdLDL, VLDL, HDL2, HDL3 and serum lipid hydroperoxides remained unchanged as a function of exercise and ageing (p > 0.05). Although regular exercise training is known to be protective against cardiovascular disease (CVD) onset, our data demonstrates that acute exercise can increase sdLDL oxidative susceptibility, and this is independent of age and regardless of a change in LDL lipid composition. However, age seems to be a determining factor with regards the susceptibility of sdLDL to oxidation 24 h following exercise.

Exercise training protects the LDL I subfraction from oxidation susceptibility in an aged human population

BackgroundExercise training is considered an effective strategy to improve metabolic disease. Despite this, less is known regarding exercise training in the prevention and susceptibility of LDL subfraction oxidation, particularly in an aged population. MethodsEleven aged (55 ± 4 yrs) and twelve young (21 ± 2 yrs) participants were randomly separated into an experimental or control group as follows: young exercise (n = 6); young control (n = 6); aged exercise (n = 6) and aged control (n = 5). The participants assigned to the exercise groups performed 12 weeks of moderate intensity (55–65% VO2max) exercise training. Venous blood was extracted at baseline, and 48 h following 12 weeks of exercise and assayed for a range of metabolites associated with lipid composition and lipoprotein susceptibility to oxidation. ResultsAlthough there was no difference in the oxidation potential (time ½ max) of LDL I, II or III between groups at baseline (p > 0.05), there was an increase in time ½ max for LDL I following exercise within the aged exercise group (p < 0.05). Moreover, α-tocopherol concentration was selectively lower in the aged exercise group, compared to the young exercise at baseline. The lipid composition of LDL I, LDL II, LDL III, VLDL, HDL2, HDL3 and serum lipid hydroperoxides remained unchanged as a function of exercise training and ageing (p > 0.05). ConclusionThe primary finding of this study demonstrates that adaptations in LDL resistance to oxidation occur following 12 weeks of exercise training in the aged, and this may be of clinical significance, as oxidation of LDL has been implicated in atherosclerosis.

Effects of lactic acid bacteria on low-density lipoprotein susceptibility to oxidation and aortic fatty lesion formation in hyperlipidemic hamsters.

We investigated the effects of Streptococcus thermophilus YIT 2001, a strain of lactic acid bacteria, on the susceptibility of low-density lipoprotein (LDL) to oxidation and the formation of aortic fatty lesions in hyperlipidemic hamsters. S. thermophilus YIT 2001 had the highest in vitro antioxidative activity against LDL oxidation among the 79 strains of lactic acid bacteria and bifidobacteria tested, which was about twice that of S. thermophilus YIT 2084. The lag time of LDL oxidation in the YIT 2001 feeding group was significantly longer than in controls, but was unchanged in the YIT 2084 group. After the feeding of YIT 2001, lag times were prolonged and areas of aortic fatty lesions were dose-dependently attenuated, although there were no effects on plasma lipid levels. These results suggest that YIT 2001 has the potential to prevent the formation of aortic fatty lesions by inhibiting LDL oxidation.

Lipoprotein-associated oxidative stress: a new twist to the postprandial hypothesis.

Oxidative stress is recognized as one of the primary processes underlying the initiation and progression of atherosclerotic vascular disease. Under physiological conditions, the balance between reactive oxygen species (ROS) generation and ROS scavenging is tightly controlled. As part of normal cellular metabolism, regulated oxidative stress is responsible for a variety of cellular responses. Excess generation of ROS that could not be compensated by antioxidant system has been suggested to be responsible for a number of pathological conditions. Due to their short biological half-lives, direct measurement of ROS is not available and surrogate measures are commonly used. Plasma lipoproteins, by virtue of their close interactions with endothelial cells in the vasculature and the susceptibility of their surface lipids to oxidative modification, are perfect biological sensors of oxidative stress in the arterial wall. In particular, with each consumed meal, triglyceride-rich lipoproteins, secreted by the intestine into the circulation, are responsible for the delivery of 20–40 grams of fat to the peripheral tissues. This flux of dietary lipids is accompanied by concomitant increases in glucose, insulin and other meal-associated metabolites. The contribution of postprandial lipemia to the pathogenesis of atherosclerosis has been previously suggested by several lines of investigation. We have extended this hypothesis by demonstrating the acute generation of oxidative epitopes on plasma lipoproteins as well as transient changes in the oxidative susceptibility of plasma lipoproteins.