Reduction of serum ubiquinol-10 and ubiquinone-10 levels by atorvastatin in hypercholesterolemic patients.
Reduction of serum cholesterol levels with statin therapy decreases the risk of coronary heart disease. Inhibition of HMG-CoA reductase by statin results in decreased synthesis of cholesterol and other products downstream of mevalonate, which may produce adverse effects in statin therapy. We studied the reductions of serum ubiquinol-10 and ubiquinone-10 levels in hypercholesterolemic patients treated with atorvastatin. Fourteen patients were treated with 10 mg/day of atorvastatin, and serum lipid, ubiquinol-10 and ubiquinone-10 levels were measured before and after 8 weeks of treatment. Serum total cholesterol and LDL-cholesterol levels decreased significantly. All patients showed definite reductions of serum ubiquinol-10 and ubiquinone-10 levels, and mean levels of serum ubiquinol-10 and ubiquinone-10 levels decreased significantly from 0.81 +/- 0.21 to 0.46 +/- 0.10 microg/ml (p < 0.0001), and from 0.10 +/- 0.06 to 0.06 +/- 0.02 microg/ml (p = 0.0008), respectively. Percent reductions of ubiquinol-10 and those of total cholesterol showed a positive correlation (r = 0.627, p = 0.0165). As atorvastatin reduces serum ubiquinol-10 as well as serum cholesterol levels in all patients, it is imperative that physicians are forewarned about the risks associated with ubiquinol-10 depletion.
J Atheroscler Thromb. 2005;12(2):111-9
Efficacy and safety of extended-release niacin alone or with atorvastatin for lipid profile modification.
OBJECTIVE: To evaluate the efficacy and safety of extended-release niacin (niacin ER) either alone or in combination with atorvastatin for the lipid profile modification in the patients with coronary heart disease (CHD) and its equivalents. METHODS: One hundred and ten patients with CHD and its equivalents with serum total cholesterol (TC) > or = 3.5 mmol/L were randomly assigned into three treatment groups: (1) atorvastatin group (n = 38), receiving atorvastatin 10 mg/d for 8 weeks; (2) niacin ER group (n = 38), given niacin ER 500 mg/d for 4 weeks and then 1000 mg/d for 4 weeks; (3) combination treatment group (n = 34), treated with atorvastatin (10 mg/d) plus niacin ER, with the dose initiating from 500 mg/d, and increasing to 1,000 mg/d after 4 weeks, for 8 weeks. The serums lipid profiles and adverse effects were assessed in all the patients before treatment, and 4 and 8 weeks after treatment. RESULTS: (1) After 8 weeks of treatment, the serum level of triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) were reduced by 30% and 16% respectively in the niacin ER group compared with the baseline values (both P < 0.05). After 8 weeks, the TC, low-density lipoprotein cholesterol (LDL-C), and TG in the atorvastatin group decreased by 19%, 26%, and 17% respectively compared with the baseline values (all P < 0.05). Combination treatment decreased the TC, LDL-C, and TG levels by 28%, 38%, and 39% respectively, and increased the HDL-C level by 23% (all P < 0.05). The improvement in TC and LDL-C achieved by combination treatment was superior to treatment of atorvastatin alone and treatment of niacin ER alone (all P < 0.05). (2) The rate of achieving the LDL-C goal of The National Cholesterol Education Program (NCEP) in Adult Treatment Panel III (ATP III) in the combination therapy group was 73.5%, significantly higher than those of the atorvastatin and niacin groups (47.7% and 42.1% respectively, both P < 0.05). (3) Adverse effect, such as flushing (15.8%) and gastrointestinal symptoms (23.7%) were found in the niacin ER group, however, no more adverse effects were found in the combination therapy group. There were no serious adverse events in all groups. CONCLUSION: Niacin ER has a favorable effect in modulating the blood lipid profile, especially in reducing TG and elevating HDL-C. Combined statin with niacin may produce a more global and effective improvement in lipid blood levels than monotherapy and is generally safe and well tolerable.
Zhonghua Yi Xue Za Zhi. 2006 Sep 12;86(34):2399-403
Effect of glucomannan on plasma lipid and glucose concentrations, body weight, and blood pressure: systematic review and meta-analysis.
BACKGROUND: Several clinical trials have investigated the impact of glucomannan on plasma lipids, body weight, fasting blood glucose (FBG), and blood pressure (BP), but have yielded conflicting results and had only modest sample sizes. OBJECTIVE: The objective was to perform a meta-analysis of randomized controlled trials of glucomannan to better characterize its impact on plasma lipids, FBG, body weight, and BP. DESIGN: A systematic literature search of MEDLINE, EMBASE, CINAHL, Web of Science, the Cochrane Library, and the Natural Medicines Comprehensive Database was conducted from the earliest possible date through November 2007. A random-effects model was used to calculate the weighted mean difference (WMD) and 95% CIs as the difference between the mean for the glucomannan and control groups. Standard methods for assessing statistical heterogeneity and publication bias were used. RESULTS: Fourteen studies (n = 531) met the inclusion criteria. The use of glucomannan significantly lowered total cholesterol [weighted mean difference (WMD): -19.28 mg/dL; 95% CI: -24.30, -14.26], LDL cholesterol (WMD: -15.99 mg/dL; 95% CI: -21.31, -10.67), triglycerides (WMD: -11.08 mg/dL; 95% CI: -22.07, -0.09), body weight (WMD: -0.79 kg; 95% CI: -1.53, -0.05), and FBG (WMD: -7.44 mg/dL; 95% CI: -14.16, -0.72). The use of glucomannan did not appear to significantly alter any other study endpoints. Pediatric patients, patients receiving dietary modification, and patients with impaired glucose metabolism did not benefit from glucomannan to the same degree. CONCLUSIONS: Glucomannan appears to beneficially affect total cholesterol, LDL cholesterol, triglycerides, body weight, and FBG, but not HDL cholesterol or BP.
Am J Clin Nutr. 2008 Oct;88(4):1167-75
Persistent and remodeling hepatic preneoplastic lesions present differences in cell proliferation and apoptosis, as well as in p53, Bcl-2 and NF-kappaB pathways.
During rat hepatocarcinogenesis preneoplastic lesions (PNL) emerge which may persist (pPNL) and be sites of progress to cancer or suffer remodeling (rPNL) tending to disappear. Cellular and molecular mechanisms involved in both phenotypes are not sufficiently elucidated. pPNL and rPNL cellular proliferation and apoptosis were evaluated in rats submitted to the resistant hepatocyte (RH) model, and an adjusted growth index (AGI) was established. p53, Bcl-2, and NF-kappaB p65 subunit expression was evaluated by immunohistochemistry in pPNL and rPNL. p65 expression and NF-kappaB activation was evaluated by Western blot assays in whole livers. A lower number of BrdU-stained hepatocyte nuclei/mm(2) and higher number of apoptotic bodies (AB) per mm(2) were observed in remodeling compared to pPNL. Cytoplasmic p53 accumulation is related to increased hepatocarcinoma malignancy. We observed that 71.3% pPNL and 25.4% rPNL (P < 0.05) presented p53 staining in the cytoplasm. Similarly, 67.7% pPNL and 23.1 % rPNL (P < 0.05) presented increased Bcl-2 staining. Thirty-two percent pPNL and 15.6% rPNL (P < 0.05) presented p65 staining. Compared to normal rats, increase (P < 0.05) of hepatic p65 expression and NF-kappaB activation in rats submitted to the RH model was observed. In agreement to previous studies hepatic pPNL and rPNL differ regarding cell proliferation and apoptosis. Moreover, persistence and remodeling involve differences in p53, Bcl-2, and NF-kappaB pathways. These data point to molecular pathways that may direct preneoplastic lesions to spontaneously regress or to progress to cancer.
J Cell Biochem. 2008 Feb 1;103(2):538-46
Inhibition of Irvingia gabonensis seed extract (OB131) on adipogenesis as mediated via down regulation of the PPARgamma and Leptin genes and up-regulation of the adiponectin gene.
BACKGROUND: Endeavors to manage obesity have been heavily reliant on controlling energy intake and expenditure equilibrium, but have failed to curtail the overweight and obesity epidemic. This dynamic equilibrium is more complex than originally postulated and is influenced by lifestyle, calorie and nutrient intake, reward cravings and satiation, energy metabolism, stress response capabilities, immune metabolism and genetics. Fat metabolism is an important indicator of how efficiently and to what extent these factors are competently integrating. We investigated whether an Irvingia gabonensis seed extract (IGOB131) would provide a more beneficial comprehensive approach influencing multiple mechanisms and specifically PPAR gamma, leptin and adiponectin gene expressions, important in anti-obesity strategies. METHODS: Using murine 3T3-L1 adipocytes as a model for adipose cell biology research, the effects of IGOB131 were investigated on PPAR gamma, adiponectin, and leptin. These adipocytes were harvested 8 days after the initiation of differentiation and treated with 0 to 250 microM of IGOB131 for 12 and 24 h at 37 degree C in a humidified 5 percent CO2 incubator. The relative expression of PPAR gamma, adiponectin, and leptin in 3T3-L1 adipocytes was quantified densitometrically using the software LabWorks 4.5, and calculated according to the reference bands of beta-actin. RESULTS: The IGOB131 significantly inhibited adipogenesis in adipocytes. The effect appears to be mediated through the down-regulated expression of adipogenic transcription factors (PPAR gamma) [P less than 0.05] and adipocyte-specific proteins (leptin) [P less than 0.05], and by up-regulated expression of adiponectin [P less than 0.05]. CONCLUSION: IGOB131 may play an important multifaceted role in the control of adipogenesis and have further implications in in-vivo anti obesity effects by targeting the PPAR gamma gene, a known contributory factor to obesity in humans.
Lipids Health Dis. 2008 Nov 13;7:44
Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein.
BACKGROUND: Increased levels of the inflammatory biomarker high-sensitivity C-reactive protein predict cardiovascular events. Since statins lower levels of high-sensitivity C-reactive protein as well as cholesterol, we hypothesized that people with elevated high-sensitivity C-reactive protein levels but without hyperlipidemia might benefit from statin treatment. METHODS: We randomly assigned 17,802 apparently healthy men and women with low-density lipoprotein (LDL) cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher to rosuvastatin, 20 mg daily, or placebo and followed them for the occurrence of the combined primary end point of myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes. RESULTS: The trial was stopped after a median follow-up of 1.9 years (maximum, 5.0). Rosuvastatin reduced LDL cholesterol levels by 50% and high-sensitivity C-reactive protein levels by 37%. The rates of the primary end point were 0.77 and 1.36 per 100 person-years of follow-up in the rosuvastatin and placebo groups, respectively (hazard ratio for rosuvastatin, 0.56; 95% confidence interval [CI], 0.46 to 0.69; P<0.00001), with corresponding rates of 0.17 and 0.37 for myocardial infarction (hazard ratio, 0.46; 95% CI, 0.30 to 0.70; P=0.0002), 0.18 and 0.34 for stroke (hazard ratio, 0.52; 95% CI, 0.34 to 0.79; P=0.002), 0.41 and 0.77 for revascularization or unstable angina (hazard ratio, 0.53; 95% CI, 0.40 to 0.70; P<0.00001), 0.45 and 0.85 for the combined end point of myocardial infarction, stroke, or death from cardiovascular causes (hazard ratio, 0.53; 95% CI, 0.40 to 0.69; P<0.00001), and 1.00 and 1.25 for death from any cause (hazard ratio, 0.80; 95% CI, 0.67 to 0.97; P=0.02). Consistent effects were observed in all subgroups evaluated. The rosuvastatin group did not have a significant increase in myopathy or cancer but did have a higher incidence of physician-reported diabetes. CONCLUSIONS: In this trial of apparently healthy persons without hyperlipidemia but with elevated high-sensitivity C-reactive protein levels, rosuvastatin significantly reduced the incidence of major cardiovascular events.
N Engl J Med. 2008 Nov 20;359(21):2195-207
Osteoclast inhibitory effects of vitamin K2 alone or in combination with etidronate or risedronate in patients with rheumatoid arthritis: 2-year results.
OBJECTIVE: To investigate the effects of vitamin K2 (Vit K2) alone or in combination with etidronate and risedronate on bone loss, osteoclast induction, and inflammation in patients with rheumatoid arthritis (RA). METHODS: Subjects comprised 79 patients with RA who were receiving prednisolone, divided into 3 groups: Group K, Vit K2 alone; Group KE, Vit K2 plus etidronate; and Group KR, Vit K2 plus risedronate. During a 24-month treatment and followup period, levels of N-terminal telopeptide of type I collagen (NTx) and bone alkaline phosphatase were measured. Bone mineral density (BMD) of the 3 groups was measured using dual-energy x-ray absorptiometry. Damage score to fingers on radiographic findings were measured according to the Larsen method. Serum levels of receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG) were measured. RESULTS: Falls in rate of change of BMD decreased after 18 months in groups KR and KE. Larsen damage scores indicated a significant difference between Group KE and other groups. Significant decreases in serum NTx were observed in groups KE and KR at all timepoints, but not in Group K. Levels of RANKL decreased significantly in all 3 groups. CONCLUSION: Vit K2 alone or in combination with bisphosphonates for treatment of osteoporosis in patients with RA may inhibit osteoclast induction via decreases in levels of RANKL.
J Rheumatol. 2008 Mar;35(3):407-13
25-hydroxyvitamin D and risk of myocardial infarction in men: a prospective study.
BACKGROUND: Vitamin D deficiency may be involved in the development of atherosclerosis and coronary heart disease in humans. METHODS: We assessed prospectively whether plasma 25-hydroxyvitamin D (25[OH]D) concentrations are associated with risk of coronary heart disease. A nested case-control study was conducted in 18,225 men in the Health Professionals Follow-up Study; the men were aged 40 to 75 years and were free of diagnosed cardiovascular disease at blood collection. The blood samples were returned between April 1, 1993, and November 30, 1999; 99% were received between April 1, 1993, and November 30, 1995. During 10 years of follow-up, 454 men developed nonfatal myocardial infarction or fatal coronary heart disease. Using risk set sampling, controls (n = 900) were selected in a 2:1 ratio and matched for age, date of blood collection, and smoking status. RESULTS: After adjustment for matched variables, men deficient in 25(OH)D (<or=15 ng/mL [to convert to nanomoles per liter, multiply by 2.496]) were at increased risk for MI compared with those considered to be sufficient in 25(OH)D (>or=30 ng/mL) (relative risk [RR], 2.42; 95% confidence interval [CI], 1.53-3.84; P < .001 for trend). After additional adjustment for family history of myocardial infarction, body mass index, alcohol consumption, physical activity, history of diabetes mellitus and hypertension, ethnicity, region, marine omega-3 intake, low- and high-density lipoprotein cholesterol levels, and triglyceride levels, this relationship remained significant (RR, 2.09; 95% CI, 1.24-3.54; P = .02 for trend). Even men with intermediate 25(OH)D levels were at elevated risk relative to those with sufficient 25(OH)D levels (22.6-29.9 ng/mL: RR, 1.60 [95% CI, 1.10-2.32]; and 15.0-22.5 ng/mL: RR, 1.43 [95% CI, 0.96-2.13], respectively). CONCLUSION: Low levels of 25(OH)D are associated with higher risk of myocardial infarction in a graded manner, even after controlling for factors known to be associated with coronary artery disease.
Arch Intern Med. 2008 Jun 9;168(11):1174-80
Independent association of low serum 25-hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality.
BACKGROUND: In cross-sectional studies, low serum levels of 25-hydroxyvitamin D are associated with higher prevalence of cardiovascular risk factors and disease. This study aimed to determine whether endogenous 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels are related to all-cause and cardiovascular mortality. METHODS: Prospective cohort study of 3,258 consecutive male and female patients (mean [SD] age, 62  years) scheduled for coronary angiography at a single tertiary center. We formed quartiles according to 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels within each month of blood drawings. The main outcome measures were all-cause and cardiovascular deaths. RESULTS: During a median follow-up period of 7.7 years, 737 patients (22.6%) died, including 463 deaths from cardiovascular causes. Multivariate-adjusted hazard ratios (HRs) for patients in the lower two 25-hydroxyvitamin D quartiles (median, 7.6 and 13.3 ng/mL [to convert 25-hydroxyvitamin D levels to nanomoles per liter, multiply by 2.496]) were higher for all-cause mortality (HR, 2.08; 95% confidence interval [CI], 1.60-2.70; and HR, 1.53; 95% CI, 1.17-2.01; respectively) and for cardiovascular mortality (HR, 2.22; 95% CI, 1.57-3.13; and HR, 1.82; 95% CI, 1.29-2.58; respectively) compared with patients in the highest 25-hydroxyvitamin D quartile (median, 28.4 ng/mL). Similar results were obtained for patients in the lowest 1,25-dihydroxyvitamin D quartile. These effects were independent of coronary artery disease, physical activity level, Charlson Comorbidity Index, variables of mineral metabolism, and New York Heart Association functional class. Low 25-hydroxyvitamin D levels were significantly correlated with variables of inflammation (C-reactive protein and interleukin 6 levels), oxidative burden (serum phospholipid and glutathione levels), and cell adhesion (vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 levels). CONCLUSIONS: Low 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels are independently associated with all-cause and cardiovascular mortality. A causal relationship has yet to be proved by intervention trials using vitamin D.
Arch Intern Med. 2008 Jun 23;168(12):1340-9
Orlistat in the treatment of overweight or obese Chinese patients with newly diagnosed Type 2 diabetes.
AIMS: Orlistat promotes weight loss in overweight and obese patients with Type 2 diabetes receiving hypoglycaemic treatment, but has not been investigated in patients with newly diagnosed and previously untreated Type 2 diabetes. We evaluated the efficacy of 24 weeks’ treatment with orlistat, combined with a mildly reduced-calorie diet, on weight loss and glycaemic control in overweight and obese patients with newly diagnosed and previously untreated Type 2 diabetes. METHODS: A total of 249 Chinese patients (body mass index 25-40 kg/m2) with recently diagnosed Type 2 diabetes were randomized to placebo (n=124) or orlistat 120 mg (n=125) three times daily; all patients followed a mildly reduced-calorie diet. Patients had HbA1c 6.5-8.5% (mean 7.3%) and had never received any glucose-lowering medication. RESULTS: Orlistat-treated patients achieved significantly greater weight loss at the study end than placebo-treated patients (-5.4 vs. -2.4 kg; P<0.0001). More orlistat than placebo patients lost>or=5% (60.5 vs. 26.8%; P<0.0001) and >or=10% of their body weight (20.2 vs. 4.9%; P=0.0002). A significantly greater decrease in HbA(1c) from baseline was obtained with orlistat than placebo (-1.0 vs. -0.6%; P=0.0008). Orlistat-treated patients achieved a significantly greater decrease in fasting plasma glucose (-1.3 vs. -0.5 mmol/l; P=0.0003) and in the 2-h oral glucose tolerance test (-4.1 vs. -1.4 mmol/l; P<0.0001) than placebo recipients. Also, more orlistat- than placebo-treated patients improved from diabetic status to normal or impaired glucose tolerance (44.3 vs. 32.5%; P=0.0763) after 24 weeks. Orlistat also produced improvements in lipid profiles and waist circumference. CONCLUSIONS: In combination with a mildly reduced-calorie diet, orlistat significantly reduces body weight, and improves glycaemic control and several cardiovascular risk factors in overweight and obese Chinese patients with newly diagnosed Type 2 diabetes.
Diabet Med. 2005 Dec;22(12):1737-43
Endogenous sex hormones and C-reactive protein in healthy postmenopausal women.
BACKGROUND: Oral oestrogen replacement therapy increases levels of C-reactive protein (CRP). CRP is an established strong predictor of cardiovascular events. It is unknown whether endogenous oestrogen levels are associated with CRP. We therefore studied the relationship between endogenous sex hormones and CRP in healthy postmenopausal women emphasizing the role of body composition as peripheral fat is both a main source of oestrogen production after menopause and an endocrine tissue with inflammatory activities. SUBJECTS AND METHODS: The study population comprised 889 women participating in the PROSPECT study, an ongoing population-based cohort study. Information on risk factors was collected by questionnaires and clinical examination. Endogenous sex hormone levels and CRP were measured with double antibody radio immuno assay (RIA) from fasting plasma samples. In this cross-sectional study, associations between risk factors and lnCRP were studied using linear regression models. RESULTS: Increases in oestrone and free oestradiol levels and the free androgen index were related to an increase in lnCRP of 1.19, 1.23 and 1.21 mg dL(-1) respectively. Body mass index (BMI), waist circumference and physical activity were strongly related to CRP levels, independent of age and other cardiovascular risk factors. Levels of all sex steroids but dehydroepiandrostenedione decreased with age. In age-adjusted analyses, an increase in waist circumference or BMI by one quartile was associated with a 1.28-fold and 1.26-fold increase in CRP. The relationship between endogenous hormones and CRP was modestly attenuated but remained highly significant after adjustment for body composition, physical activity and other traditional cardiovascular risk factors. CONCLUSIONS: Our findings show that in postmenopausal women high levels of endogenous oestrogenic and androgenic sex steroids coincide with high CRP levels. This was only explained in part by markers of body composition or intra-abdominal fat.
J Intern Med. 2008 Sep;264(3):245-53
Advanced age is associated with endothelial dysfunction in healthy elderly subjects.
BACKGROUND: Aging is associated with an increased risk for atherosclerosis in which endothelial dysfunction is an early marker. OBJECTIVE: The purpose of this study was to determine if endothelial function is altered with increasing age in healthy subjects. METHOD: The study population consisted of 30 elderly and 36 younger subjects free from major cardiovascular risk factors. Transthoracic echocardiography was performed for each subject to rule out structural heart disease. Endothelial function was evaluated by flow-mediated dilation (FMD) of the brachial artery via ultrasound. RESULTS: Baseline characteristics of the elderly and the younger group were similar, except for age (mean age: 71.3 +/- 5.8 vs. 26.5 +/- 7.2). Transthoracic echocardiography was normal in all subjects. FMD of the elderly group was significantly lower than the younger group (7.9 +/- 3.1 in the elderly, 10.8 +/- 1.9 in the younger group, p < 0.001). A negative relationship was found between FMD and age (r = -0.528, p < 0.001). CONCLUSION: It can be concluded that endothelial function detected by FMD declines with increasing age in healthy human subjects. Advanced age is a predictor of impaired endothelial function.
How do dietary flavanols improve vascular function? A position paper.
Epidemiological and clinical studies revealed that high-flavanol diet or isolated (-)-epicatechin improves the function of the vascular endothelium, as assessed by flow-mediated dilation, through elevation of bioavailability and bioactivity of NO*. We have demonstrated that exposure of human endothelial cells to (-)-epicatechin elevates the cellular levels of NO* and cyclic GMP and protects against oxidative stress elicited by proinflammatory agonists. (-)-Epicatechin acts like a prodrug, since these effects involve O-methylation of the flavanol and are attributed to apocynin-like inhibition of endothelial NADPH oxidase. Thus, generation of superoxide and peroxynitrite is diminished and, consequently, the cellular NO* level is preserved or augmented. We propose therefore that endothelial NO* metabolism rather than general antioxidant activity is a major target of dietary flavanols and that NADPH oxidase activity is a crucial site of action. Moreover, flavonoid glucuronides appear to serve as plasma transport metabolites to target cells rather than solely as excretion products. Implications for the interpretation of the role of dietary polyphenols for cardiovascular health are discussed.
Arch Biochem Biophys. 2008 Aug 15;476(2):102-6
Oxidation of LDL and its clinical implication.
Oxidative modification of low-density lipoprotein (LDL) is one of the earliest events in atherosclerosis. Oxidized LDL (oxLDL) represents a variety of modification of both lipid and apolipoprotein B (apoB) components by lipid peroxidation. This promotes atherosclerosis through inflammatory and immunologic mechanisms that lead to the formation of macrophage foam cells. Recent findings also suggest that oxLDL forms complexes with beta(2)-glycoprotein I (beta(2)GPI) and/or C-reactive protein (CRP) within atherosclerotic lesions and that these complexes appear in the circulation. Autoantibodies (auto-Abs) against oxLDL/beta(2)GPI complexes occur in patients with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). These autoantibodies significantly correlate with arterial thrombosis. IgG auto-Abs having similar specificity emerge spontaneously in NZWxBXSB F1 mice, which generally are considered to be an animal model of APS, and these mice produce a monoclonal IgG auto-Ab (WB-CAL-1) against oxLDL/beta(2)GPI complexes. WB-CAL-1 significantly increased the in vitro uptake of oxLDL/beta(2)GPI complexes by macrophages, which suggests that such IgG auto-Abs are pro-atherogenic. In contrast, IgM anti-oxLDL natural Abs found in the atherosclerosis-prone mice have been proposed to be protective. The presence of such Abs in humans has been documented in many publications but their exact pathophysiological significance remains unclear. In this article, we review recent progress in our understanding of the clinical significance of oxidation of LDL, formation of oxLDL complexes, and Abs in atherosclerotic and/or autoimmune disease.
Autoimmun Rev. 2008 Jul;7(7):558-66
Comparison of lycopene and fluvastatin effects on atherosclerosis induced by a high-fat diet in rabbits.
OBJECTIVE: We evaluated the antiatherogenic effect of lycopene in rabbits fed a high-fat diet. METHODS: Forty adult male rabbits were divided into five groups that were fed a standard diet, a high-fat diet, a high-fat diet plus 4 mg/kg of lycopene, a high-fat diet plus 12 mg/kg of lycopene, and a high-fat diet plus 10 mg/kg of fluvastatin, respectively. Lycopene and fluvastatin were administered intragastrically. The level of serum total cholesterol, total triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total antioxidant capacity, and malondialdehyde were measured before and after 4 and 8 wk of experimental treatment. In addition, plasma levels of lycopene, oxidized low-density lipoprotein, serum nitric oxide, and interleukin-1 were measured after the experiment. The area of atherosclerotic plaque and pathologic changes of the aorta were evaluated. RESULTS: Compared with the control, levels of total cholesterol, total triacylglycerol, low-density lipoprotein cholesterol, malonaldehyde, oxidized low-density lipoprotein, and interleukin-1 were increased and total antioxidant capacity and nitric oxide were decreased in the animals with a high-fat diet (P < 0.05). Intragastric administration of lycopene counteracted the change in these parameters (P < 0.05). In this case, the data showed that lycopene in the used dose was better than the fluvastatin intervention. Morphologic analysis revealed that lycopene and fluvastatin markedly reduced the formation of atherosclerotic plaques in the aorta compared with the situation in rabbits on a high-fat diet alone. CONCLUSION: Lycopene, like fluvastatin, significantly attenuated atherogenesis in rabbits fed a high-fat diet.
Nutrition. 2008 Oct;24(10):1030-8