Showing papers on "High-density lipoprotein published in 2005"

New insights into the regulation of HDL metabolism and reverse cholesterol transport.

Abstract: The metabolism of high-density lipoproteins (HDL), which are inversely related to risk of atherosclerotic cardiovascular disease, involves a complex interplay of factors regulating HDL synthesis, intravascular remodeling, and catabolism. The individual lipid and apolipoprotein components of HDL are mostly assembled after secretion, are frequently exchanged with or transferred to other lipoproteins, are actively remodeled within the plasma compartment, and are often cleared separately from one another. HDL is believed to play a key role in the process of reverse cholesterol transport (RCT), in which it promotes the efflux of excess cholesterol from peripheral tissues and returns it to the liver for biliary excretion. This review will emphasize 3 major evolving themes regarding HDL metabolism and RCT. The first theme is that HDL is a universal plasma acceptor lipoprotein for cholesterol efflux from not only peripheral tissues but also hepatocytes, which are a major source of cholesterol efflux to HDL. Furthermore, although efflux of cholesterol from macrophages represents only a tiny fraction of overall cellular cholesterol efflux, it is the most important with regard to atherosclerosis, suggesting that it be specifically termed macrophage RCT. The second theme is the critical role that intravascular remodeling of HDL by lipid transfer factors, lipases, cell surface receptors, and non-HDL lipoproteins play in determining the ultimate metabolic fate of HDL and plasma HDL-c concentrations. The third theme is the growing appreciation that insulin resistance underlies the majority of cases of low HDL-c in humans and the mechanisms by which insulin resistance influences HDL metabolism. Progress in our understanding of HDL metabolism and macrophage reverse cholesterol transport will increase the likelihood of developing novel therapies to raise plasma HDL concentrations and promote macrophage RCT and in proving that these new therapeutic interventions prevent or cause regression of atherosclerosis in humans.

Low serum level of high-density lipoprotein cholesterol is a poor prognostic factor for severe sepsis.

Abstract: OBJECTIVE To assess the initial serum levels of lipids and lipoproteins and their correlations with the clinical outcome for patients with severe sepsis. The ability of high-density lipoprotein (HDL) to attenuate lipopolysaccharide (LPS)-induced cytokine production was also examined in vitro. DESIGN Prospective, observational cohort study. SETTING Medical intensive care unit (ICU) of a tertiary-level university hospital. PATIENTS Sixty-three consecutive patients with severe sepsis. INTERVENTIONS Blood samples were drawn within the first day of severe sepsis and the subsequent 14 days. Clinical outcome, including length of ICU stay, infection subsequent to hospital stay, and death, were monitored prospectively. MEASUREMENTS AND RESULTS Compared with the survivors, patients who died within 30 days had significantly lower levels of HDL cholesterol and apolipoprotein A-I during the first 4 days of severe sepsis. On day 1, HDL cholesterol levels correlated inversely with interleukin-6 (r = -0.72; p 7 days) and the hospital-acquired infection rate were increased among patients with day 1 levels of HDL cholesterol of <20 mg/dL and apolipoprotein A-I of <100 mg/dL. Multivariate analysis identified an HDL cholesterol level of <20 mg/dL on day 1 (odds ratio, 12.92; 95% confidence interval, 2.73-61.29) and Acute Physiology and Chronic Health Evaluation II score (odds ratio, 1.15; 95% confidence interval, 1.04-1.26) as independent predictors of the overall 30-day mortality rate. In human macrophages, LPS-induced TNF-alpha release was attenuated by incremental doses of HDL cholesterol added simultaneously (p < .01). However, HDL failed to suppress LPS-induced TNF-alpha production when administered after macrophages were exposed to LPS. CONCLUSIONS A low HDL cholesterol level on day 1 of severe sepsis is significantly associated with an increase in mortality and adverse clinical outcomes. In cultured macrophages, HDL can attenuate LPS-induced TNF-alpha production only if added concomitantly with, but not after, LPS exposure.

Lipoproteomics II: Mapping of proteins in high‐density lipoprotein using two‐dimensional gel electrophoresis and mass spectrometry

Abstract: The molecular mechanisms underlying the relationship between low-density lipoprotein (LDL) and the risk of atherosclerosis are not clear. Therefore, detailed information about the protein composition of LDL may contribute to reveal its role in atherogenesis and the mechanisms that lead to coronary disease in humans. Here, we sought to map the proteins in human LDL by a proteomic approach. LDL was isolated by two-step discontinuous density-gradient ultracentrifugation and the proteins were separated with two-dimensional gel electrophoresis and identified with peptide mass fingerprinting, using matrix assisted laser desorption/ionization-time of flight-mass spectrometry and with amino acid sequencing using electrospray ionization tandem mass spectrometry. These procedures identified apo B-100, apo C-II, apo C-III (three isoforms), apo E (four isoforms), apo A-I (two isoforms), apo A-IV, apo J and apo M (three isoforms not previously described). In addition, three proteins that have not previously been identified in LDL were found: serum amyloid A-IV (two isoforms), calgranulin A, and lysozyme C. The identities of apo M, calgranulin A, and lysozyme C were confirmed by sequence information obtained after collision-induced dissociation fragmentation of peptides characteristic for these proteins. Moreover, the presence of lysozyme C was further corroborated by demonstrating enriched hydrolytic activity in LDL against Micrococcus lysodeikticus. These results indicate that in addition to the dominating apo B-100, LDL contains a number of other apolipoproteins, many of which occur in different isoforms. The demonstration, for the first time, that LDL contains calgranulin A and lysozyme C raises the possibility that LDL proteins may play hitherto unknown role(s) in immune and inflammatory reactions of the arterial wall.

Effects of Cholesteryl Ester Transfer Protein Inhibition on High-Density Lipoprotein Subspecies, Apolipoprotein A-I Metabolism, and Fecal Sterol Excretion

Abstract: Objective— Pharmacological inhibition of the cholesteryl ester transfer protein (CETP) in humans increases high-density lipoprotein (HDL) cholesterol (HDL-C) levels; however, its effects on apolipoprotein A-I (apoA-I) containing HDL subspecies, apoA-I turnover, and markers of reverse cholesterol transport are unknown. The present study was designed to address these issues. Methods and Results— Nineteen subjects, 9 of whom were taking 20 mg of atorvastatin for hypercholesterolemia, received placebo for 4 weeks, followed by the CETP inhibitor torcetrapib (120 mg QD) for 4 weeks. In 6 subjects from the nonatorvastatin cohort, the everyday regimen was followed by a 4-week period of torcetrapib (120 mg BID). At the end of each phase, subjects underwent a primed-constant infusion of (5,5,5-2H3)-l-leucine to determine the kinetics of HDL apoA-I. The lipid data in this study have been reported previously. Relative to placebo, 120 mg daily torcetrapib increased the amount of apoA-I in α1-migrating HDL in the atorvastatin (136%; P <0.001) and nonatorvastatin (153%; P <0.01) cohorts, whereas an increase of 382% ( P <0.01) was observed in the 120 mg twice daily group. HDL apoA-I pool size increased by 8±15% in the atorvastatin cohort ( P =0.16) and by 16±7% ( P <0.0001) and 34±8% ( P <0.0001) in the nonatorvastatin 120 mg QD and BID cohorts, respectively. These changes were attributable to reductions in HDL apoA-I fractional catabolic rate (FCR), with torcetrapib reducing HDL apoA-I FCR by 7% ( P =0.10) in the atorvastatin cohort, by 8% ( P <0.001) in the nonatorvastatin 120 mg QD cohort, and by 21% ( P <0.01) in the nonatorvastatin 120 mg BID cohort. Torcetrapib did not affect HDL apoA-I production rate. In addition, torcetrapib did not significantly change serum markers of cholesterol or bile acid synthesis or fecal sterol excretion. Conclusions— These data indicate that partial inhibition of CETP via torcetrapib in patients with low HDL-C: (1) normalizes apoA-I levels within α1-migrating HDL, (2) increases plasma concentrations of HDL apoA-I by delaying apoA-I catabolism, and (3) does not significantly influence fecal sterol excretion.

A Randomized Trial of a Strategy for Increasing High-Density Lipoprotein Cholesterol Levels: Effects on Progression of Coronary Heart Disease and Clinical Events

Abstract: The authors compared a combination drug regimen designed to increase high-density lipoprotein cholesterol levels (gemfibrozil, niacin, and cholestyramine) plus counseling about diet and exercise to...

High-density lipoprotein, but not low-density lipoprotein cholesterol levels influence short-term prognosis after acute coronary syndrome: results from the MIRACL trial

Abstract: Aims Patients with acute coronary syndrome (ACS) in the Myocardial Ischaemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study had diminished cardiovascular events after 16 weeks of treatment of atorvastatin 80 mg daily. We determined whether plasma lipoproteins at baseline and then at 6 weeks after randomization predicted clinical outcome. Methods and results Cox proportional hazards models were constructed to determine relations between lipoproteins and clinical endpoint events. Baseline LDL cholesterol (LDL-C) did not predict outcome. In contrast, baseline HDL-C predicted outcome with a hazard ratio of 0.986 per mg/dL increment in HDL-C, P <0.001, indicating 1.4% reduction in risk for each 1 mg/dL increase in HDL-C. Atorvastatin treatment profoundly lowered LDL-C, but had minimal effect on HDL-C. Neither Week 6 LDL-C nor absolute change of LDL-C from baseline by Week 6 had any significant impact on clinical endpoints occurring between Week 6 and Week 16 after randomization. Conclusion Plasma HDL-C, but not LDL-C, measured in the initial stage of ACS predicts the risk of recurrent cardiovascular events over the ensuing 16 weeks. LDL-C reduction does not account for the clinical risk reduction with atorvastatin treatment after ACS. This finding may suggest that the clinical benefit of atorvastatin after ACS is mediated by qualitative changes in the LDL particle and/or by non-lipid (pleiotropic) effects of the drug.

Dental infections and cardiovascular diseases: a review.

Abstract: Accumulating evidence suggests that chronic infections, such as periodontitis, are associated with increased risk for cardiovascular diseases (CVD). The mechanisms behind the association are not known. Like herpes viruses and Chlamydia pneumoniae, periodontal pathogens cause atherosclerosis in experimental animals and have been found in human atherosclerotic lesions. Higher concentrations of total and low density lipoprotein (LDL) cholesterol and triglycerides and lower concentrations of high density lipoprotein (HDL) cholesterol have been observed in individuals with periodontitis before periodontal treatment. Periodontitis also induces a peripheral inflammatory and immune response, reflected in elevated concentrations of C-reactive protein (CRP) and IgA-class antibodies to periodontal pathogens. The prevalence of CVD seems to be highest in those individuals in whom periodontitis coexists with elevated CRP levels. This may indicate that periodontitis is a CVD risk factor in individuals who react to the infection with a systemic inflammatory and immune response. This may be due to genetic reasons and may also apply to other chronic low-grade infections.

High-Density Lipoprotein Deficiency and Dyslipoproteinemia Associated With Venous Thrombosis in Men

Abstract: Background-Although dyslipoproteinemia is associated with arterial atherothrombosis, little is known about plasma lipoproteins in venous thrombosis patients. Methods and Results-We determined plasma lipoprotein subclass concentrations using nuclear magnetic resonance spectroscopy and antigenic levels of apolipoproteins AI and B in blood samples from 49 male venous thrombosis patients and matched controls aged <55 years. Venous thrombosis patients had significantly lower levels of HDL particles, large HDL particles, HDL cholesterol, and apolipoprotein AI and significantly higher levels of LDL particles and small LDL particles. The quartile-based odds ratios for decreased HDL particle and apolipoprotein AI levels in patients compared with controls were 6.5 and 6.0 (95% CI, 2.3 to 19 and 2.1 to 17), respectively. Odds ratios for apolipoprotein B/apolipoprotein AI ratio and LDL cholesterol/HDL cholesterol ratio were 6.3 and 2.7 (95% CI, 1.9 to 21 and 1.1 to 6.5), respectively. When polymorphisms in genes for hepatic lipase, endothelial lipase, and cholesteryl ester transfer protein were analyzed, patients differed significantly from controls in the allelic frequency for the TaqI B1/B2 polymorphism in cholesteryl ester transfer protein, consistent with the observed pattern of lower HDL and higher LDL. Conclusions-Venous thrombosis in men aged <55 years old is associated with dyslipoproteinemia involving lower levels of HDL particles, elevated levels of small LDL particles, and an elevated ratio of apolipoprotein B/apolipoprotein AI. This dyslipoproteinemia seems associated with a related cholesteryl ester transfer protein genotype difference. © 2005 American Heart Association, Inc.

Impact of Short-Term Administration of High-Density Lipoproteins and Atorvastatin on Atherosclerosis in Rabbits

Abstract: Objective— This study investigates effects of short-term administration of high-density lipoproteins (HDL) and a statin on atherosclerosis in cholesterol-fed rabbits. Effects of HDL apolipoprotein and phospholipid composition have also been investigated. Methods and Results— Aortic atherosclerosis was established over 17 weeks in 46 rabbits by balloon denudation and cholesterol feeding. During the past 5 days of the cholesterol-feeding period, animals received: (1) no treatment; (2) oral atorvastatin 5 mg/kg on each of the 5 days; or (3) infusions of HDL (8 mg/kg apolipoprotein A-I) on days 1 and 3 of the treatment phase. After euthanization, lesion size and composition were assessed by histological and immunohistochemical analysis. HDL (but not atorvastatin) reduced lesion size by 36% ( P P P P P P Conclusion— Infusing small amounts of HDL rapidly reduces lesion size and is comparable to atorvastatin in promoting a stable plaque phenotype.

Apolipoproteins modulate the inflammatory response to lipopolysaccharide

Abstract: An increasing body of evidence demonstrates a close interplay between lipoprotein metabolism and sepsis. Sepsis results in an increase of plasma triglycerides within VLDL as a consequence of an enhanced hepatic VLDL production and/or inhibited peripheral and hepatic VLDL clearance. In contrast, sepsis decreases plasma cholesterol within LDL and mainly HDL. The decrease in HDL is accompanied by a loss of mainly apoAI-containing particles, an almost total loss of apoCI, and an increase in apoE-containing HDL, as related to the effect of LPS on a wide range of apolipoproteins, plasma enzymes, lipid transfer factors, and receptors that are involved in HDL metabolism. Reciprocally, all lipoprotein classes have been shown to bind LPS and to attenuate the biological response to LPS in vitro and in rodents. Moreover, triglyceride-rich lipoproteins protect rodents against death from LPS and bacterial sepsis. Accumulating evidence indicates that apolipoproteins such as apoE and apoAI, and not the lipid moieties of the particles, may be responsible for these protective effects of lipoproteins. Therefore, to increase our understanding of the complex interaction between lipoprotein metabolism and sepsis, further studies that address the specific roles of apolipoproteins in sepsis are warranted.

The role of dietary oxidized cholesterol and oxidized fatty acids in the development of atherosclerosis.

Abstract: The etiology of atherosclerosis is complex and multifactorial but there is extensive evidence indicating that oxidized lipoproteins may play a key role. At present, the site and mechanism by which lipoproteins are oxidized are not resolved, and it is not clear if oxidized lipoproteins form locally in the artery wall and/or are sequestered in atherosclerotic lesions following the uptake of circulating oxidized lipoproteins. We have been focusing our studies on demonstrating that such potentially atherogenic oxidized lipoproteins in the circulation are at least partially derived from oxidized lipids in the diet. Thus, the purpose of our work has been to determine in humans whether oxidized dietary oxidized fats such as oxidized fatty acids and oxidized cholesterol are absorbed and contribute to the pool of oxidized lipids in circulating lipoproteins. When a meal containing oxidized linoleic acid was fed to normal subjects, oxidized fatty acids were found only in the postprandial chylomicron/chylomicron remnants (CM/RM) which were cleared from circulation within 8 h. No oxidized fatty acids were detected in low density lipoprotein (LDL) or high density lipoprotein (HDL) fractions at any time. However, when alpha-epoxy cholesterol was fed to human subjects, alpha-epoxy cholesterol in serum was found in CM/RM and also in endogenous very low density lipoprotein, LDL, and HDL and remained in the circulation for 72 h. In vitro incubation of the CM/RM fraction containing alpha-epoxy cholesterol with human LDL and HDL that did not contain alpha-epoxy cholesterol resulted in a rapid transfer of oxidized cholesterol from CM/RM to both LDL and HDL. We have suggested that cholesteryl ester transfer protein is mediating the transfer. Thus, alpha-epoxy cholesterol in the diet is incorporated into CM/RM fraction and then transferred to LDL and HDL contributing to lipoprotein oxidation. We hypothesize that diet-derived oxidized fatty acids in chylomicron remnants and oxidized cholesterol in remnants and LDL accelerate atherosclerosis by increasing oxidized lipid levels in circulating LDL and chylomicron remnants. This hypothesis is supported by our feeding experiments in animals. When rabbits were fed oxidized fatty acids or oxidized cholesterol, the fatty streak lesions in the aorta were increased by 100%. Moreover, dietary oxidized cholesterol significantly increased aortic lesions in apo-E and LDL receptor-deficient mice. A typical Western diet is rich in oxidized fats and therefore could contribute to the increased arterial atherosclerosis in our population.

Rationale for using apolipoprotein B and apolipoprotein A-I as indicators of cardiac risk and as targets for lipid-lowering therapy

Abstract: This editorial refers to ‘Prognostic value of apolipoprotein B and A-I in the prediction of myocardial infarction in middle-aged men and women: results from the MONICA/KORA Augsburg cohort study’† by C. Meisinger et al. , on page 271 Although low density lipoprotein (LDL) is recognized as the primary lipid-related risk factor, and therefore the primary target for lipid-lowering therapy,1–4 there are in fact several limitations of only using LDL cholesterol (LDL-C) as the primary risk variable.5,6 New data are accumulating which speak in favour of apolipoproteins (apo) as more informative risk indicators/factors. ApoB, which indicates the number of potentially atherogenic lipoprotein particles, and apoA-I, which reflects anti-atherogenic high density lipoprotein (HDL) particles, may be additional lipid-related variables that more accurately indicate cardiovascular (CV) risk than LDL-C. Thus, several studies have shown that apoB and apoA-I are strong predictors of myocardial infarction (MI).7–9 The two largest of these studies are the AMORIS7 and the INTERHEART9 studies which both show a very strong direct relation between a high apoB/apoA-I ratio and an increased risk of fatal MI7 and acute MI (AMI).9 Meisinger et al. 10 add another piece of important information along the same lines. ### Physiological and pathophysiological aspects of apoB and apoA-I metabolism ApoB is present in very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), large buoyant LDL, and small dense LDL (sd-LDL), with one molecule of apoB in each of these atherogenic particles. Thus, total apoB reflects the total number of atherogenic particles ( Figure 1 ). It is the apoB in the particles that leads to entrapment of these lipoproteins in the arterial wall. ApoB produced in the liver also stabilizes and allows the transport of cholesterol and triglycerides in plasma VLDL, IDL, large buoyant LDL, and sd-LDL ( Figure 1 ). In addition, apoB serves as the ligand … *Corresponding author. E-mail address : goran.walldius{at}astrazeneca.com

The "Good Cholesterol" High-Density Lipoprotein

Abstract: Atherosclerosis is an insidious and dangerous disease: a progressive chemical and structural injury to the blood vessels in such critical organs as the heart, brain, and kidney. The hallmark feature of atherosclerosis is the buildup of cholesterol into lesions called plaques that can reduce the flow of blood. When the delivery of blood to heart muscle drops enough, this can result in the development of chest pain or angina. Angina indicates that the heart muscle is not receiving enough oxygen to carry out its pumping functions. Atherosclerotic plaques can also suddenly rupture, develop a blood clot on their surface, and completely choke off a portion of heart muscle. This chain of events frequently results in heart attack or sudden death without warning. Atherosclerotic disease also predisposes people to stroke, peripheral vascular disease, lower-extremity amputation, and loss of kidney function, among other devastating outcomes. Despite all that we have learned in the past 50 years, atherosclerosis remains the No. 1 killer of men and women and the chief reason for loss of quality of life in Western countries. We are, however, gaining ground. Considerable research has revealed the importance of factors that increase an individual’s risk for developing this disease. Among the most important of these risk factors are elevated blood pressure, diabetes mellitus, obesity, inactivity, smoking, and cholesterol levels. When your physician measures your cholesterol level, he or she is looking at your lipid profile, which comprises low-density lipoprotein cholesterol (LDL-C, or the “bad” cholesterol), triglycerides (blood fats), and high-density lipoprotein cholesterol (HDL-C, or the “good” cholesterol). In a general way, when it comes to measurement of your LDL-C and triglyceride values, a lower value is better because these lipids drive the development and progression of atherosclerosis. In sharp contrast, when it …

Elevated high-density lipoprotein cholesterol levels are protective against plaque progression : A follow-up study of 1952 persons with carotid atherosclerosis the tromsø study

Abstract: Background— There is an inverse relationship between HDL cholesterol and coronary heart disease. Experimental studies have indicated that HDL cholesterol may exert an antiatherogenic effect by indu...

Lipid responses to a dietary docosahexaenoic acid supplement in men and women with below average levels of high density lipoprotein cholesterol.

Abstract: Objective: To assess fasting lipid responses to a docosahexaenoic acid (DHA) supplement in men and women with below-average levels of high-density lipoprotein (HDL) cholesterol.Methods: This randomized, double-blind, controlled clinical trial included 57 subjects, 21–80 years of age, with fasting HDL cholesterol concentrations ≤44 mg/dL (men) and ≤54 mg/dL (women), but ≥35 mg/dL. Subjects were randomly assigned to receive either 1.52 g/day DHA from capsules containing DHA-rich algal triglycerides or olive oil (control) for six weeks.Results: There were no significant differences between groups in baseline lipid values. The DHA supplemented group showed significant changes [−43 (DHA) vs. −14 (controls) mg/dL, p = 0.015] and percent changes [−21% (DHA) vs. −7% (controls), p = 0.009] in triglycerides, total (12 vs. 3 mg/dL; p = 0.021 and 6% vs. 2%; p = 0.018) and low-density lipoprotein (17 vs. 3 mg/dL; p = 0.001 and 12% vs. 3%; p = 0.001) cholesterol concentrations, and in the triglyceride to HDL cholestero...

High-density lipoprotein as a therapeutic target: clinical evidence and treatment strategies.

Abstract: The clinical importance of low serum levels of high-density lipoprotein (HDL) cholesterol is often under-recognized and underappreciated as a risk factor for premature atherosclerosis as well as for cardiovascular morbidity and mortality. Low serum levels of HDL are frequently encountered, especially in patients who are obese or have the metabolic syndrome. In prospective epidemiologic studies, every 1-mg/dL increase in HDL is associated with a 2% to 3% decrease in coronary artery disease risk, independent of low-density lipoprotein (LDL) cholesterol and triglyceride (TG) levels. The primary mechanism for this protective effect is believed to be reverse cholesterol transport, but several other anti-inflammatory, antithrombotic, and antiproliferative functions for HDL have also been identified. In recognition of these antiatherogenic effects, recent guidelines have increased the threshold for defining low levels of HDL for both men and women. The first step in achieving these revised targets is therapeutic lifestyle changes. When these measures are inadequate, pharmacotherapy specific to the patient's lipid profile should be instituted. Niacin therapy, currently the most effective means for raising HDL levels, should be initiated in patients with isolated low HDL (HDL <40 mg/dL, LDL and non-HDL at or below National Cholesterol Education Program (NCEP) targets based on global cardiovascular risk evaluation). Patients who have both low HDL and elevated LDL should receive a statin or statin-niacin combination therapy, and patients with concomitant low HDL and elevated TGs should receive a fibrate initially, with a statin, niacin, or ezetimibe added thereafter as needed to help attain NCEP lipoprotein targets.

Phytopreventative anti-hyperlipidemic effects of gynostemma pentaphyllum in rats

Abstract: Purpose: Gynostemma pentaphyllum is widely used in traditional Chinese medicine. Preliminary studies indicate Gynostemma isolated triterpine glycosides lower cholesterol. Our studies examine anti-hyperlipidemic effects of gypenosides. Methods: Gynostemma activity was examined in poloxamer P407 induced hyperlipidemia in rats. Results: 1 g/kg P407 induced plasma triglyceride (25 fold), total cholesterol (6 fold), low density lipoprotein cholesterol (LDL) (7 fold), high density lipoprotein cholesterol (HDL) (1.6 fold), and nitrite (8 fold). After acute (4 days) and chronic (12 days) oral administration the gypenoside extract (250 mg/kg) reduced triglyceride (53% and 85%, respectively) and total cholesterol levels (10% and 44%, respectively). No significant effects on LDL or HDL cholesterol were observed. The gypenosides reduced nitrite ~80%. Similar results were obtained with atorvastatin (75 mg/kg for 4 days); except that LDL cholesterol was reduced (17%) and HDL cholesterol increased. 50% of lipoprotein lipase (LPL) plasma activity was inhibited by ~20 μM P407. Gynostemma had no effect on LL, however, it reversed the P407 inhibition of LPL activity in a concentration-dependent manner, with a 2-fold increase at ~10 μg/ml. Conclusions: These studies demonstrate efficacy of Gynostemma pentaphyllum in lowering triglyceride, cholesterol and nitrite in acute hyperlipidemia. The results suggest further investigations of Gynostemma gypenosides are warranted to examine the mechanisms of this activity.

Hypocholesterolemic effects of a flavonoid-rich extract of Hypericum perforatum L. in rats fed a cholesterol-rich diet.

Abstract: In a previous study, a flavonoid-rich extract of Hypericum perforatum L. (FEHP) was prepared and its antioxidant activity was determined by a series of models in vitro. In this study, the hypocholesterolemic effects of FEHP in rats fed a cholesterol-rich diet were tested. Forty Wistar rats fed a standard laboratory diet or a cholesterol-rich diet for 16 weeks were used. The serum lipid levels, as well as malondialdehyde (MDA) and activity of superoxide dismutase (SOD) and catalase (CAT) in serum and liver, were examined. Cholesterol-rich diet induced hypercholesterolemia was manifested in the elevation of serum lipid levels such as total cholesterol (TC), total triglycerides (TG), and low density lipoprotein cholesterol (LDL-C). Administration of middle-dose (75 mg/kg of BW/day) and high-dose (150 mg/kg of BW/day) FEHP significantly lowered the serum levels of TC, TG, and LDL-C, while increasing the serum level of high density lipoprotein cholesterol (HDL-C). Also, the content of MDA in serum and liver decreased significantly after oral administration of FEHP compared with those of rats fed a cholesterol-rich diet. In addition, FEHP increased the activity of SOD in serum and liver, but the activity of CAT was significantly elevated only in liver. These results suggested that the hypocholesterolemic effects of FEHP might be due to its abilities to lower serum TC, TG, and LDL-C levels as well as to slow the lipid peroxidation process and to enhance the antioxidant enzyme activity.

Adverse effects of danazol prophylaxis on the lipid profiles of patients with hereditary angioedema.

Abstract: Background Hereditary angioedema (HAE) is a rare disorder caused by the deficiency of the C1-inhibitor gene (C1INH) Patients experience recurrent bouts of edema, which can occur in almost any region of the body As regards the treatment of the disease, danazol (an attenuated androgen) is used, among other agents, for long-term prophylaxis Objective The aim of this study was to investigate the possible adverse effects of danazol on serum lipid profile, as well as to ascertain whether danazol treatment is associated with an increased risk of atherosclerosis Methods Serum concentrations of total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, apolipoprotein A-I, apolipoprotein B-100, and lipoprotein(a) were compared between danazol-treated patients with HAE and 2 control groups (ie, patients who did not receive long-term danazol prophylaxis and untreated healthy subjects) Results Serum concentrations of HDL ( P =0002 and P P =0015 and P P =0129 and P =0127) and apolipoprotein B-100 ( P =0456 and P =0013) were higher in the danazol-treated patients compared with the 2 control groups, respectively No significant difference was found in total cholesterol, triglyceride, or lipoprotein(a) levels Patients who received danazol had an 116 (95% CI, 27-497) times higher risk for abnormally low HDL levels and a 44 (95% CI, 12-160) times lower risk for high LDL concentrations Conclusions Our findings indicate that the long-term use of danazol is associated with an increased risk for early atherosclerosis in patients with HAE Consequently, monitoring of HDL and LDL levels at regular intervals is recommended during follow-up