Plasma LDL Levels Research Articles

PREDICTORS OF IN-STENT RESTENOSIS AND PATIENT OUTCOME AFTER PERCUTANEOUS CORONARY INTERVENTION IN DIABETES MELLITUS.

Background Diabetics have a significantly higher incidence of major adverse cardiac events (MACE) and in-stent restenosis (ISR) than nondiabetics after percutaneous coronary intervention (PCI). Predictors of MACE and ISR are uncertain in diabetics. There are few data about the association of microalbuminuria and diabetic retinopathy with MACE and ISR. Methods We studied 195 patients (63 ± 9 years, 98% males) with diabetes mellitus who underwent PCI. We investigated ISR and incidence of MACE (cumulative of myocardial infarction, revascularization, and deaths from cardiac causes) in these patients; all patients were on statins. Results Of 195 patients, 107 had follow-up catheterization at a mean of 16 months. Of these 107 patients, 56 developed ISR. In the multivariate model, microalbuminuria or diabetic retinopathy did not have any significant association with ISR (OR = 0.659, CI 0.247-1.75, p = .40 and OR = 2.02, CI 0.64-6.37, p = .22, respectively) or MACE (OR = 1.342, CI 0.7-2.55, p = .37 and OR = 0.945, CI 0.437-2.04, p = .88, respectively). Plasma level of HDL cholesterol was inversely associated with the incidence of ISR (OR −0.928, CI 0.876-0.983, p = .011) and MACE (OR −0.965, CI 0.931-1, p = .048). Use of a Cypher stent (vs bare metal stent) had a negative association with ISR (OR −0.171, CI 0.05-0.585, p = .004). The presence of renal disease was associated with higher MACE (OR 3.19, CI 1.45-7.031, p = .0039). The multivariate model was adjusted for the size of the target vessel, complexity of lesion, type of stent, and plasma LDL levels. Conclusion HDL cholesterol level is inversely associated with ISR and MACE after PCI in high-risk diabetic patients. However, microalbuminuria or diabetic retinopathy are not associated with ISR or MACE.

Lp(a) enhances coronary atherosclerosis in transgenic Watanabe heritable hyperlipidemic rabbits

Elevated plasma levels of LDL and lipoprotein (a) [Lp(a)] are associated with an increased risk of atherosclerosis and coronary heart disease. However, it is not known whether Lp(a) would enhance the atherogenic effect of LDL on coronary atherosclerosis and myocardial infarction. To address this issue, we cross-bred human Lp(a) transgenic (Tg) rabbits with Watanabe heritable hyperlipidemic (WHHL) rabbits and evaluated the long-term (at the age of 2 years) effects of Lp(a) on the development of coronary atherosclerosis. Compared to non-Tg WHHL rabbits, Tg WHHL rabbits did not show significant changes in plasma total cholesterol, triglycerides, or HDL-C. However, Tg WHHL rabbits showed significantly larger lesions in the right coronary arteries ( p < 0.05). Immunohistochemical staining revealed that the lesions of Tg WHHL rabbits were enriched in the extracellular matrix contents whereas the cellular components were not different from those in non-Tg WHHL rabbits. Increased atherosclerosis in the coronary arteries in Tg WHHL rabbit hearts was also associated with a higher incidence of chronic ischemia and myocardial infarction. These results suggest that increased plasma levels of Lp(a) enhance coronary atherosclerosis and myocardial infarction in the setting of hypercholesterolemia.

Increased Aldosterone/Renin Quotient in Obese Hypertensive Women: A Novel Role for Low-density Lipoproteins?

Obesity, especially visceral obesity, is strongly associated with arterial hypertension. Indeed, obesity hypertension has to be considered as the most common form of essential hypertension. However, the exact nature of the relationship between obesity and increased blood pressure remains poorly understood. Involvement of renin-independent mechanisms has been suggested in adrenal stimulation of aldosterone secretion in obese patients. This investigation examined the plasma levels of renin, aldosterone, insulin, and HDL and LDL in obese hypertensive and obese normotensive women. The group of hypertensive obese women showed significantly reduced plasma levels of renin and increased aldosterone/renin quotient (ARQ) compared to obese normotensive women. Plasma aldosterone levels were not significantly different between hypertensive and normotensive obese women. In addition, plasma levels of LDL-cholesterol in the hypertensive obese group were significantly increased in comparison to the obese normotensive group. No differences were observed in HDL-cholesterol or total cholesterol/HDL-C ratios between the two groups. We therefore examined the effect of LDL on angiotensin II-stimulated aldosterone release from human adrenocortical H295R cells. Treatment of adrenocortical cells with LDL led to a sensitization towards stimulation by angiotensin II, dramatically increasing angiotensin II-induced aldosterone production, so the increased aldosterone/renin ratio observed in the hypertensive group may be due to the enhanced LDL levels in these patients and/or other adipocyte-derived mineralocorticoid-stimulating factors.

Aggressive Very Low-Density Lipoprotein (VLDL) and LDL Lowering by Gene Transfer of the VLDL Receptor Combined with a Low-Fat Diet Regimen Induces Regression and Reduces Macrophage Content in Advanced Atherosclerotic Lesions in LDL Receptor-Deficient Mice

Very low-density lipoprotein (VLDL) and LDL plasma levels are associated with cardiovascular mortality. Whereas VLDL/LDL lowering causes regression of early atherosclerotic lesions, less is known about the effects of aggressive lipid lowering on regression of advanced complex lesions. We therefore investigated the effect of VLDL/LDL lowering on pre-existing lesions in LDL receptor-deficient mice. Mice fed a high-fat diet for 16 weeks developed advanced lesions with fibrous caps, necrotic cores, and cholesterol clefts in the brachiocephalic artery. After an additional 14 weeks on a low-fat diet, plasma cholesterol levels decreased from 21.0 +/- 2.6 to 8.4 +/- 0.6 mmol/L, but lesions did not regress. Levels of VLDL/LDL were further lowered by using a helper-dependent adenovirus encoding the VLDL receptor (HD-Ad-VLDLR) under control of a liver-selective promoter. Treatment with HD-Ad-VLDLR together with a low-fat diet regimen resulted in reduced lesion size (cross-sectional area decreased from 146,272 +/- 19,359 to 91,557 +/- 15,738 microm2) and an 89% reduction in the cross-sectional lesion area occupied by macrophages compared to controls. These results show that aggressive VLDL/LDL lowering achieved by hepatic overexpression of VLDLR combined with a low-fat diet regimen induces regression of advanced plaques in the brachiocephalic artery of LDL receptor-deficient mice.

Possible connections among job stress, depressive symptoms, lipid modulation and antioxidants

Background Oxidative/antioxidative status may be related to psychological stress or pathogenesis of depression. Subjects and methods Participants were selected from 381 female nurses working in a university hospital, and the Brief Job Stress Questionnaire was utilized to assess them. Nurses with high job stress (JS) ( n = 18) and with low JS ( n = 15) consented to participate in this study. Depressive symptoms were assessed by the Centre for Epidemiologic Studies Depression scale (CES-D). Cholesterols, lipid peroxidation (malondialdehyde, MDA) and antioxidants in the plasma were measured. Results High JS participants exhibited significantly higher CES-D scores ( t = 3.34, p < 0.005), and significantly lower concentrations of total cholesterol (TC), low density + very low density lipoprotein cholesterols (LDL + VLDL), α-tocopherol, and β-carotene compared with low JS participants ( t = 2.69, p < 0.05; t = 3.46, p < 0.005; t = 2.96, p < 0.05; t = 2.98, p < 0.05, respectively). However, the reductions in plasma indicators were substantially weakened after controlling for lifestyle factors with the exception of LDL + VLDL and α-tocopherol. In addition, the significance of α-tocopherol concentrations appeared to depend on cholesterol levels. CES-D scores correlated positively with plasma MDA levels, the MDA / TC ratio and the MDA / LDL + VLDL ratio among the low JS group ( r = 0.69, p < 0.001; r = 0.79, p < 0.001; r = 0.75, p < 0.005, respectively), whereas there were no correlations among the high JS group. After controlling for lifestyle covariates, the relationship between CES-D scores and the MDA / LDL + VLDL ratio remained significant ( β = 0.95, p < 0.05) using a multiple linear regression model ( F = 3.61, p < 0.05). Limitations Sample numbers in each JS group were relatively small. Conclusions Psychological stress may reduce the plasma levels of LDL + VLDL accompanying an α-tocopherol decrease. There appeared to be a correlation between elevated MDA and depressive symptoms in low JS participants.

Plasma Paraoxonase Activities, Lipoprotein Oxidation, and Trace Element Interaction in Asthmatic Patients

Paraoxonase (PON1) protects low and high-density lipoproteins (LDL and HDL) against oxidation induced by reactive oxygen species formation facilitated by iron (Fe) and copper (Cu) ions. Plasma PON1, arylesterase, oxidized LDL (Ox-LDL), Cu, Fe, thiobarbituric acid-reactive substances (TBARS), lipid, lipoprotein, and apolipoprotein profile in bronchial asthma were determined and the relations among these parameters in different steps of asthma were interpreted. A total of 58 individuals, 30 asthmatics and 28 controls, were included into the scope of this study. Plasma PON1, arylesterase, and TBARS levels were measured spectrophotometrically. Determination of plasma oxidized LDL, Cu, and Fe levels were performed by enzyme-linked immunosorbent assay, atomic absorption spectrophotometry, and the automated TPTZ method, respectively. Apo-A-1 and Apo-B levels were determined immunoturbidometrically. Plasma total cholesterol, triglyceride, and HDL cholesterol levels were enzymatically determined. Plasma LDL levels were estimated using the Fridewald formula. The average plasma PON1 and arylesterase activities in the group of patients were lower than those of the individuals in the control group, but there was no statistically significant difference found between them (p > 0.05). No significant difference was found in plasma Apo-A-1, Apo-B, total cholesterol, triglyceride, HDL, and LDL concentrations between the control and patient groups (p > 0.05). Plasma oxidized LDL (p < 0.05), Cu (p < 0.01), Fe (p < 0.01), and TBARS (p < 0.001) levels in patients with asthma were found to be significantly higher than for the control group. Increases in Cu, Fe, lipid peroxidation, and oxidized LDL levels supported by relative decreases in PON1 activities observed in asthmatic patients might be introduced as the striking findings as well as the possible potential indicators of this airway disease, the prevalence of which has increased dramatically over recent decades.

Mo-P5:304 Effects of exercise training on LDL plasma removal and on oxidized LDL plasma levels in hypercholesterolemia

Mo-P5:304 Effects of exercise training on LDL plasma removal and on oxidized LDL plasma levels in hypercholesterolemia

APOC3/A5 haplotypes, lipid levels, and risk of myocardial infarction in the Central Valley of Costa Rica

Genetic variation in the APOC3 and APOA5 genes has been associated with plasma triglyceride concentrations and may affect the risk of myocardial infarction (MI). To assess whether APOC3/A5 haplotypes are associated with risk of MI, we examined three single-nucleotide polymorphisms (SNPs) in APOC3 (3238C>G, -455T>C, and -482C>T) and six SNPs in the APOA5 gene (-1131T>C, c.-3A>G, c.56C>G, IVS3+476G>A, c.553G>T, and c.1259T>C) in incident cases (n = 1,703) of a first nonfatal MI matched for gender, age, and area of residence with population-based controls (n = 1,703). Conditional logistic regression models, adjusted for potential environmental confounders, were used for analysis. The common APOC3*222 haplotype was more frequent in cases than in controls (17.4% and 13.7%, respectively, P < 0.001) and was associated with increased risk of MI [odds ratio (OR) = 1.27; 95% confidence interval (95% CI), 1.09, 1.48] compared with APOC3*111 wild-type haplotype. This association was independent of the APOA5 SNPs. Although the APOC3 3238G, APOA5 -1131C, APOA5 c.-3G, and APOA5 c.1259C alleles were associated with higher triglyceride plasma concentrations, these effects could not explain the associations with MI in this population. In summary, this study supports the hypothesis that haplotypes in the APOC3 gene but not in the APOA5 gene increase susceptibility to MI.

Thematic Review Series: The Immune System and Atherogenesis. Molecular mechanisms regulating monocyte recruitment in atherosclerosis

Cardiovascular disease, a progressive disorder characterized by the accumulation of lipids in the artery wall, is a leading cause of death in Western societies. One of the initial events in atherogenesis involves the recruitment of inflammatory cells from the circulation into the developing lesion. Studies during the past decade have underscored the role of inflammatory mediators in disease initiation and progression. Critical progress has been made in our understanding of the complex mechanisms by which monocytes, macrophages, and T-cells accumulate in atherosclerotic plaques. Experimental research has identified several candidate adhesion proteins and chemokines that are critically involved in the recruitment process, and encouraging data provide a mechanistic framework for new therapeutic targets. This review provides an overview of our current understanding of the mechanisms that direct the recruitment of monocytes to, and their retention in, atherosclerotic lesions.

Saturated fat–rich diet enhances selective uptake of LDL cholesteryl esters in the arterial wall

Plasma LDL levels and atherosclerosis both increase on a saturated fat-rich (SAT) diet. LDL cholesterol delivery to tissue may occur via uptake of the LDL particles or via selective uptake (SU), wherein cholesteryl ester (CE) enters cells without concomitant whole-particle uptake. It is not known how dietary fats might directly affect arterial LDL-CE uptake and whether SU is involved. Thus, mice that are relatively atherosclerosis resistant (C57BL/6) or susceptible to atherosclerosis (apoE) were fed a chow or SAT diet and injected with double radiolabeled or fluorescent-labeled human LDL to independently trace LDL-CE core and whole-particle uptake, respectively. Our results show that a SAT diet increased contributions of SU to total arterial LDL-CE delivery in C57BL/6 and apoE mice. The SAT diet increased plasma fatty acid and cholesterol levels; cholesterol, but not fatty acid, levels correlated with SU, as did the degree of atherosclerosis. Increased SU did not correlate with arterial scavenger receptor class B type I levels but paralleled increased lipoprotein lipase (LPL) levels and LPL distribution in the arterial wall. These studies suggest that arterial LDL-CE delivery via SU can be an important mechanism in vivo and that dietary influences on arterial LPL levels and atherogenesis modulate arterial LDL-CE delivery, cholesterol deposition, and SU.

Native and oxidized low-density lipoproteins stimulate endothelin-converting enzyme-1 expression in human endothelial cells

This study addressed the question how different lipoproteins modulate the expression of endothelin-converting enzyme-1 (ECE-1) in human endothelial cells. The effect of native and oxidized low-density lipoproteins (nLDL, oxLDL) on expression of ECE-1, prepro-endothelin-1, and endothelin-1 peptide was studied in primary cultures of human endothelial cells. Native and oxidized LDL increased ECE-1 mRNA after 1 h, reaching its maximum at 100 μg/ml (1.9- and 2.5-fold, respectively). Furthermore, ECE-1 protein expression, prepro-endothelin-1 mRNA, and endothelin-1 peptide release were increased in response to nLDL or oxLDL. Induction of ECE-1 by nLDL and of prepro-endothelin-1 by oxLDL was reduced by protein kinase C inhibition. Increased expression of ECE-1 mRNA by oxLDL and of prepro-endothelin-1 by nLDL was blocked by an angiotensin II receptor type 1 antagonist. Our data provide evidence for a new mechanism how increased LDL plasma levels might contribute to enhanced endothelin-1 release in patients with hypercholesterolemia.

The relationship between lipid profile and erectile dysfunction

The objective of this study is to investigate the relation between serum lipids (cholesterol, LDL, HDL, triglyceride (TG)) and erectile dysfunction (ED). The experimental methods involved comparison of 100 patients with organic ED (mean age of 43.59+/-10.51 y), with 100 healthy individuals (mean age of 43.72+/-9.76 y) regarding their lipid profile from January 2000 to June 2003 (cholesterol, TG, HDL, LDL). The results showed that there was a significant difference between mean plasma cholesterol and LDL levels in the individuals suffering from ED and the control group (P=0.04 and 0.02, respectively). The TG and HDL mean plasma level differences were not significant (P=0.583 and 0.299, respectively). Odds ratios for high plasma cholesterol level (>240 mg/dl) and high plasma LDL level (>160 mg/dl) were 1.74 and 1.97. The R2 was 0.04 for both cholesterol and LDL. Applying linear regression, the coefficient for cholesterol and LDL reduced the International Index of Erectile Function questionnaire scores by -0.036 and -0.035. In conclusion, this study, the correlation of cholesterol and LDL levels with ED strongly supports the role of hyperlipidemia treatment in both the prevention and management of ED.

Optimization of the therapeutic procedure during LDL-apheresis—a computerized model

LDL-apheresis is a very effective method for the treatment of resistant hypercholesterolemia when other therapy (dietary, or medication) fails. To maximize the efficacy of the LDL-absorbers we aimed to create a computerized model. Patients and methods: The therapeutic technique of immunoadsorption was used, applying a pair of columns, the Lipopak ®, Pocard, Russia. Plasma was separated by a continuous-flow plasma separator, the Cobe Spectra, USA; adsorption was controlled by adsorption–desorption equipment, ADA, Medicap, Germany. 494 LDL-apheresis procedures (treatment interval 17.5 ± 1.6 days) were used to treat nine patients with primary hypercholesterolemia followed during the consecutive 3.6 ± 0.5 years. Metabolism of LDL-cholesterol is known to be multicompartmental and dynamic, but for the short-time period of the procedure it can be simplified and one can calculate the procedure as a continuous filtration. We developed a program for procedure planning, using Microsoft ® Excel for Windows. Inputs inserted into the program include only basic patient data (mass, height, sex and initial plasma LDL level in mmol/l). Results: The results show a very promising match between our planning of the procedures and the real laboratory results. The drop in calculated vs real plasma LDL-cholesterol level differ no more than ±10%. Conclusions: Although our software does not take into account many well known details about the metabolism of cholesterol, in given conditions it can provide a fairly precise prediction of procedure parameters. It is also suitable for practical use, because it requires only a few commonly used and readily available input values. Immunoadsorption with Pocard absorbers is a potent and safe method of therapy in indicated patients.

LDL receptor expression on T lymphocytes in old patients with Down syndrome

BackgroundIn Down syndrome patients several metabolic abnormalities have been reported, some involving the lipid metabolism. The level of LDL in plasma is the major determinant of the risk of vascular disease. There appear to be no studies on the LDL receptor in Down syndrome patients.MethodsFlow cytometric methods for measuring the LDL receptor in peripheral blood mononuclear cells (PBMC) can identify patients with hypercholesterolemia. We applied this method in 19 old patients with Down syndrome and 23 healthy controls.ResultsDown syndrome patients had high levels of triglycerides and low levels of HDL, and high levels of CRP. We also found a down-regulation of LDL receptor expression.ConclusionsDown syndrome patients show no increase in the frequency of cardiovascular disease. The low incidence in cardiovascular disease despite the low level of HDL, high levels of CRP and reduction of LDL receptor expression lead to the conclusion that either these are not risk factors in these patients or that other risks factors – not yet identified – are considerably lower.

Pravastatin reduces thrombogenicity by mechanisms beyond plasma cholesterol lowering

Inhibitors of 3-hydroxy-3-methylglutaryl coenzymeA reductase are widely used in the management and prevention of cardiovascular disease. In addition to its major activity, plasma lipid lowering, statins have shown a wide spectrum of additional effects that may contribute to their benefits in the prevention of cardiovascular disease. Our objective was to study whether treatment with a statin, pravastatin, could reduce thrombosis triggered by damaged vessels without changing plasma cholesterol levels. A cholesterol-clamp animal model was developed by feeding swine for 100 days on an hypercholesterolemic (HL) diet; in the last 50 days, they were randomly assigned to receive either placebo (HLC) or pravastatin (5 mg . kg(-1) . day(-1)) (HLP) in addition to the hypercholesterolemic diet. A normocholesterolemic control group (NLC) was simultaneously studied. There were no significant differences in total cholesterol, LDL and HDL plasma levels between the two groups; however, mural thrombosis triggered by both an eroded and disrupted vessel wall was significantly inhibited by pravastatin (P<0.05). Axial dependence analysis of platelet deposition revealed that pravastatin treatment reduced the increase in platelet deposition associated to the shear rate increase at the stenosis. Additionally, pravastatin treatment significantly reduced platelet membrane RhoA expression (P<0.05) and vascular wall tissue factor (TF) protein expression (P<0.05). In addition to its lipid lowering effects, pravastatin can reduce blood thrombogenicity by mechanisms independent of plasma cholesterol lowering.

Can worms defend our hearts? Chronic helminthic infections may attenuate the development of cardiovascular diseases

The established risk factors for atherosclerosis fail to fully explain the extent and severity of coronary artery diseases in 50% of the patients. Thus, the causative agents and processes, which may be involved in the pathogenesis of atherosclerosis, are being sought. Notoriously, atherosclerosis and cardiovascular event rates are much lower in developing countries. Clinically, severe infections by intracellular pathogens are widespread mostly in developing countries with poor sanitation, nutrition and massive worm infections. A link between atherosclerosis and helminth infections has never been examined. Based on the present knowledge of immune and infectious mechanisms related to atherosclerosis, it is proposed that chronic helminthic infections can have a significant bearing on the epidemiology of cardiovascular diseases. How can helminthic infections affect the cardiovascular risk? (1) Helminths evade or suppress host immune responses, by producing anti-inflammatory and other immunomodulatory molecules. (2) Helminths induce chronic Th2 activation, which can modify cytokine profiles and immunological responses to heat shock proteins, Chlamydia pneumoniae and cytomegalovirus. (3) The chronic Th2 profile may modulate monocyte activation and chemotaxis to inflammatory sites (atherosclerotic plaques). (4) Chronic Th2 activation may lead to a cytokine profile that could be beneficial for attenuation of atherosclerosis development (upregulation of IL-4, IL-10 and IL-13 and downregulation of proinflammatory cytokines). (5) Helminthic infections may reduce plasma LDL level not only by affecting the host nutrition, but also via modulation of naturally occurring antibodies to cholesterol. Studies are needed to clarify these suggestions. If the hypothesis that helminthic infections impact atherosclerosis is correct, it should be taken into consideration in atherosclerosis immunomodulation therapy and especially in the design of vaccines and vaccine trials.

The Effect of Dietary Fat on LDL Size Is Influenced by Apolipoprotein E Genotype in Healthy Subjects

LDL particle size is dependent on both genetic factors and environmental factors such as dietary fat composition. The apolipoprotein E (apoE) genotype is a major genetic determinant of LDL size. Thus, the aim of this work was to study whether the apoE genotype interacts with the quantity and quality of dietary fat, modifying LDL size in young healthy subjects. Healthy subjects (n = 84; 66 apoE 3/3, 8 apoE 4/3, 10 apoE 3/2) were subjected to 3 dietary periods, each lasting 4 wk. The first was an SFA-enriched diet (38% fat, 20% SFA), which was followed by a carbohydrate (CHO)-rich diet (30% fat, < 10% SFA, 55% carbohydrate) or a monounsaturated fatty acid (MUFA) olive oil-rich diet (38% fat, 22% MUFA) following a randomized crossover design. At the end of each diet period, LDL particle size and plasma levels of total cholesterol, LDL cholesterol (LDL-C), HDL-C, apoB, apoA-I, and triacylglycerols were determined. LDL particle size was significantly higher (P < 0.04) in subjects with the apoE 4/3 genotype compared with those with apoE 3/3 and apoE 3/2 in the basal state. LDL size was smaller (P < 0.02) after the CHO diet than after the MUFA or SFA diets. After the CHO diet, a significant increase in LDL particle size (P < 0.035) was noted with respect to the MUFA diet in apoE 4/3 subjects, whereas a significant decrease was observed in the apoE 3/3 individuals (P < 0.043). In conclusion, a Mediterranean diet, high in MUFA-fat increases LDL particle size compared with a CHO diet, and this effect is dependent of apoE genotypes.

Effects of exercise training and detraining on oxidized low-density lipoprotein-potentiated platelet function in men

Wang J-S, Chow S-E. Effects of exercise training and detraining on oxidized low-density lipoprotein-potentiated platelet function in men. Arch Phys Med Rehabil 2004;85:1531–7. Objective To investigate how exercise training and detraining affect oxidized low-density lipoprotein (Ox-LDL)-potentiated platelet function in men. Design Cohort study. Setting Department of physical medicine and rehabilitation. Participants Ten sedentary men (mean age ± standard error of the mean, 21.6±0.2y) who did not engage in any regular physical activity for at least 1 year before the study. Interventions Subjects cycled on an ergometer at about 50% of maximal oxygen consumption for 30 minutes daily, 5 days a week, for 8 weeks, then detrained for 12 weeks. Main outcome measures During the experimental period, blood samples from the subjects were collected before and immediately after a progressive exercise test (ie, strenuous, acute exercise) every 4 weeks. The following measurements were taken when the subjects were at rest and immediately after exercise: plasma lipid profile, plasma Ox-LDL level, and platelet aggregation and intracellular calcium concentration ([Ca 2+] i) elevation induced by adenosine disphosphate (ADP) alone or simultaneous ADP and Ox-LDL addition. Results Analytical results indicated that: (1) plasma total cholesterol and LDL levels were reduced after exercise training from 151±7mg/dL and 58±2mg/dL to 133±6mg/dL and 46±2mg/dL ( P<.05), respectively, whereas the plasma Ox-LDL level remained unchanged; (2) platelet aggregation and [Ca 2+] i elevation promoted by 100μg/mL of Ox-LDL were significantly increased from 70%±5% and 91%±7% of resting level to 108%±4% and 125%±3% after strenuous, acute exercise ( P<.05); (3) exercise training decreased resting and postexercise 100μg/mL Ox-LDL-potentiated platelet aggregation (ie, 31%±4% and 82%±4%, respectively; P<.05) and [Ca 2+] i elevation (ie, 35%±6% and 71%±4%, respectively; P<.05); (4) detraining reversed the training effects on lipid profile and platelet function; and (5) treating the platelet with L-arginine-inhibited Ox-LDL-potentiated platelet activation during the experimental period. Conclusions Our results suggest that 8 weeks of exercise training decreased the plasma LDL level, but failed to influence production of plasma Ox-LDL. Importantly, resting and exercise-induced Ox-LDL-potentiated platelet activation was decreased by exercise training. However, this was reversed by detraining to the pretraining level.

Sports Requiring Stressful Physical Exertion Cause Abnormalities in Plasma Lipid Profile

To study the effect of different types of sports on plasma lipid profile. Subjects and method. Fasting plasma levels of total, LDL- and HDL-cholesterol (TC, LDLc, HDLc), triglycerides, phospholipids, apo A-I, apo B-100, and Lp(a) were measured in 28 swimmers, 17 volleyball players and 23 soccer players, and in a control group. All subjects participated in official national competitions except the control group. The results were compared to those in a control group of 26 healthy sedentary subjects. All groups were matched according to age, body mass index and nutritional status. Cutoff points to classify subjects with high plasma concentrations of Lp(a) and LDLc were 32 mg/dL and 128 mg/dL, respectively. For other variables the cutoff points were the third quartile values recorded in the control group, except for apo A-I and HDLc, for which we used the first quartile values. Persons who practice sports involving a high level of physical exertion (volleyball and soccer players) had a less favorable lipid profile compared to control subjects. In contrast, swimmers had a more favorable lipid profile. The odds ratio for lipid profile anomalies was significantly higher in volleyball and soccer players, and lower in swimmers. In the former two groups we observed a clear tendency toward simultaneous elevations in LDLc, apo B-100 and Lp(a). In contrast, the opposite interaction was seen in swimmers, who had lower values for all lipids. Our results show that stressful physical exertion can lead to abnormalities in plasma lipid profile.

Genome-Wide Scan Identifies Novel QTLs for Cholesterol and LDL Levels in F2[Dahl R×S]-Intercross Rats

Hypercholesterolemia is a significant risk factor for coronary artery disease development. Genes influencing nonmonogenic hypercholesterolemia susceptibility in humans remain to be identified. Animal models are key investigative systems because major confounding variables such as diet, activity, and genetic background can be controlled. We performed a 121-marker, total genome-analysis of an F2[Dahl RxS]-intercross selected for contrasting parental strain susceptibilities for hyperlipidemia on regular rat diets at 6 months of age. Quantitative traits studied were plasma total cholesterol, triglyceride, HDL, and LDL levels adjusted for obesity. Genome-wide analysis of 200 F2-intercross male rats detects two QTLs with highly significant linkage for total cholesterol (TC) on chromosome (chr) 5-133.3 Mbp (LOD 5.8), and chr5-54.2 Mbp (LOD 4.8), and two QTLs with significant linkage for TC: on chromosome 8, chr8-60.4 Mbp (LOD 3.8), and chromosome 2, chr2-243.5 Mbp (LOD 3.4). A QTL for LDL with significant linkage is detected on chromosome 5, chr5-104 Mbp (LOD 3.7). These QTLs contribute from 7% to 12% of total trait variance, respectively, with Dahl-S allele effects resulting in increased TC and LDL levels consistent with hyperlipidemia susceptibility in the parental Dahl-S rat strain. Predicted QTL-peaks do not coincide with previous genome scans. Human homologues of two TC-QTLs span genes listed in a LocusLink profile for cholesterol. Only suggestive loci were detected for HDL and total triglyceride levels. Altogether, the data demonstrates the contribution of multiple QTLs to hypercholesterolemia making a multipathway pathogenic framework imperative. QTL-peak candidate genes delineated are syntenic between rat and human genomes, increasing clinical relevance and mandating further study.