Plasma High-density Lipoprotein Levels Research Articles

Sphingosine-1-phosphate: metabolism, transport, atheroprotection and effect of statin treatment.

To better define the metabolism of sphingosine-1-phosphate (S1P), its transport in plasma and its interactions with S1P receptors on vascular cells, and to evaluate the effect of statin treatment on the subnormal plasma levels of high-density lipoprotein (HDL)-bound S1P characteristic of the atherogenic dyslipidemia of metabolic syndrome (MetS). Neither clinical intervention trials targeted to raising high-density lipoprotein-cholesterol (HDL-C) levels nor human genome-wide association studies (GWAS) studies have provided evidence to support an atheroprotective role of HDL. Recently however a large monogenic univariable Mendelian randomization on the N396S mutation in the gene encoding endothelial lipase revealed a causal protective effect of elevated HDL-C on coronary artery disease conferred by reduced enzyme activity. Given the complexity of the HDL lipidome and proteome, components of HDL other than cholesterol may in all likelihood contribute to such a protective effect. Among HDL lipids, S1P is a bioactive sphingolipid present in a small proportion of HDL particles (about 5%); indeed, S1P is preferentially enriched in small dense HDL3. As S1P is bound to apolipoprotein (apo) M in HDL, such enrichment is consistent with the elevated apoM concentration in HDL3. When HDL/apoM-bound S1P acts on S1P1 or S1P3 receptors in endothelial cells, potent antiatherogenic and vasculoprotective effects are exerted; those exerted by albumin-bound S1P at these receptors are typically weaker. When HDL/apoM-bound S1P binds to S1P2 receptors, proatherogenic effects may potentially be induced. Subnormal plasma levels of HDL-associated S1P are typical of dyslipidemic individuals at high cardiovascular risk and in patients with coronary heart disease. International Guidelines recommend statin treatment as first-line lipid lowering therapy in these groups. The cardiovascular benefits of statin therapy are derived primarily from reduction in low-density lipoprotein (LDL)-cholesterol, although minor contributions from pleiotropic actions cannot be excluded. Might statin treatment therefore normalize, directly or indirectly, the subnormal levels of S1P in dyslipidemic subjects at high cardiovascular risk? Our unpublished findings in the CAPITAIN study (ClinicalTrials.gov: NCT01595828), involving a cohort of obese, hypertriglyceridemic subjects (n = 12) exhibiting the MetS, showed that pitavastatin calcium (4 mg/day) treatment for 180days was without effect on either total plasma or HDL-associated S1P levels, suggesting that statin-mediated improvement of endothelial function is not due to normalization of HDL-bound S1P. Statins may however induce the expression of S1P1 receptors in endothelial cells, thereby potentiating increase in endothelial nitric oxide synthase response to HDL-bound S1P, with beneficial downstream vasculoprotective effects. Current evidence indicates that S1P in small dense HDL3 containing apoM exerts antiatherogenic effects and that statins exert vasculoprotective effects through activation of endothelial cell S1P1 receptors in response to HDL/apoM-bound S1P.

Antihyperlipidemic, hypoglycaemic and antioxidative potential of Juglans Regia (walnuts) in an experimental animal model of dietary hyperlipidemia.

Background: Cardiovascular diseases (CVD) are recognized as the world's primary cause of fatality, particularly in the developing countries. Stroke and ischemic heart disease have reportedly been the principal manifestations of vascular disease mainly because of the gradual increase in the incidence of the risk factors. In this aspect, the present study is planned to investigate the cardio-protective potential of Juglans regia (JR) (walnuts) consumption in controlling dyslipidemia. JR has notable therapeutic effects and, it has been used since ancient times for its anti-inflammatory, cardio-protective, and anti-bacterial properties.
 Methodology: In this study, 32 age-matched females, Wistar albino rats of 5-6 weeks weighing 200 g, were selected and equally divided into four experimental groups. Group I was used as control, Group II was positively induced hyperlipidemia through a high-fat diet; Group III animals were fed normal rat chow along with 153 mg JR powder, and Group IV animals have also inducted hyperlipidemia through a high-fat diet incorporated with 153 mg JR powder/Kg for 15 days. Bodyweight changes along with daily diet consumption were measured on alternate days.
 Results: In comparison to the control group, animals fed with a high-fat diet (Group II) showed a non-significant increase in plasma lipid profile, total cholesterol (TC), triglycerides (TG), and plasma high-density lipoprotein (HDL) levels. Group III and IV animals, after walnut powder supplementation, showed a significant decrease in lipid profile change in very Low-Density Lipoprotein levels (VLDL) of 10.3 ± 0.60 mg/dl and 12.27 ± 0.94 mg/dl together with nephron-protective & reno-protective enzymatic alterations. Histological analysis revealed signs of inflammation in high fat treated groups while well-maintained cardiac tissues within walnut treated groups, respectively.
 Conclusion: Daily consumption of Juglans Regia (walnut) in the dosage mentioned earlier is beneficial in protectively modulating dyslipidemia, hyperglycemic, and oxidative tissue potential of high-fat diet consumption in an experimental animal model.

The impact of sleep apnea syndrome on the altered lipid metabolism and the redox balance

BackgroundObstructive sleep apnea (OSA) is a disorder with a significant risk for cardiovascular diseases. Dyslipidemia and redox imbalance belong to potential mechanisms linking OSA with the development of vascular diseases. The main aim of this study was the evaluation of the presence of lipid abnormalities in OSA patients, focusing on small dense low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions and determination of the redox imbalance by evaluating the marker of oxidative damage to plasma lipids - lipoperoxides.MethodsThe study included 15 male subjects with polysomnographically confirmed OSA and 16 male healthy controls. Plasma levels of total cholesterol, LDL and HDL and their subfractions, triacylglycerols and lipoperoxides were determined in all study individuals. Plasma LDL and HDL subfractions were separated by the Lipoprint system which is a polyacrylamide gel electrophoresis. Lipoperoxide levels were determined spectrophotometrically.ResultsOSA patients had significantly higher triacylglycerols, total cholesterol and LDL-cholesterol compared to healthy controls. HDL cholesterol was not significantly different. Of the LDL and HDL subfractions, OSA patients had significantly lower levels of atheroprotective LDL1 and large HDL subfractions and significantly higher levels of atherogenic small dense LDL3–7 and HDL8–10 subfractions. Lipoperoxide levels in patients with OSA were significantly elevated compared to healthy individuals.ConclusionThe lipoprotein pro-atherogenic phenotype was found in individuals with OSA characterized by increased levels of atherogenic lipoprotein subfractions and reduced levels of atheroprotective subfractions. In addition, a plasma redox imbalance was found in patients with OSA compared to controls by detecting higher oxidative damage to lipids. Abnormalities in lipoprotein levels in patients with OSA, as well as the redox imbalance, could lead to an acceleration of the atherosclerotic process in predisposed individuals and thus represent a significant risk factor for vasular diseases.

Identification of the RORα Transcriptional Network Contributes to the Search for Therapeutic Targets in Atherosclerosis.

The retinoic acid receptor-related orphan receptor α (RORα) is involved in the regulation of several physiological processes, including development, metabolism, and circadian rhythm. RORα-deficient mice display profound atherosclerosis, in which hypoalphalipoproteinemia is reportedly associated with decreased plasma levels of high-density lipoprotein, increased levels of inflammatory cytokines, and ischemia/reperfusion-induced damage. The recent characterization of endogenous ligands (including cholesterol, oxysterols, provitamin D3, and their derivatives), mediators, and initiation complexes associated with the transcriptional regulation of these orphan nuclear receptors has facilitated the development of synthetic ligands. These findings have also highlighted the potential of application of RORα as a therapeutic target for several diseases, including diabetes, dyslipidemia, and atherosclerosis. In this review, the current literature related to the structure and function of RORα, its genetic inter-individual differences, and its potential as a therapeutic target in atherosclerosis is discussed.

Integrative Analyses Reveal Tstd1 as a Potential Modulator of HDL Cholesterol and Mitochondrial Function in Mice.

High-density lipoprotein (HDL) cholesterol levels are closely associated with human health and diseases. To identify genes modulating plasma HDL levels, we integrated HDL measurements and multi-omics data collected from diverse mouse cohorts and combined a list of systems genetics methods, including quantitative trait loci (QTL) mapping analysis, mediation analysis, transcriptome-wide association analysis (TWAS), and correlation analysis. We confirmed a significant and conserved QTL for plasma HDL on chromosome 1 and identified that Tstd1 liver transcript correlates with plasma HDL in several independent mouse cohorts, suggesting Tstd1 may be a potential modulator of plasma HDL levels. Correlation analysis using over 70 transcriptomics datasets in humans and mice revealed consistent correlations between Tstd1 and genes known to be involved in cholesterol and HDL regulation. Consistent with strong enrichment in gene sets related to cholesterol and lipoproteins in the liver, mouse strains with high Tstd1 exhibited higher plasma levels of HDL, total cholesterol and other lipid markers. GeneBridge using large-scale expression datasets identified conserved and positive associations between TSTD1/Tstd1 and mitochondrial pathways, as well as cholesterol and lipid pathways in human, mouse and rat. In summary, we identified Tstd1 as a new modulator of plasma HDL and mitochondrial function through integrative systems analyses, and proposed a new mechanism of HDL modulation and a potential therapeutic target for relevant diseases. This study highlights the value of such integrative approaches in revealing molecular mechanisms of complex traits or diseases.

Hematological Parameters, Lipid Profile, and Cardiovascular Risk Analysis Among Genotype-Controlled Indigenous Kiwcha Men and Women Living at Low and High Altitudes.

Introduction: Human adaptation to high altitude is due to characteristic adjustments at every physiological level. Differences in lipid profile and cardiovascular risk factors in altitude dwellers have been previously explored. Nevertheless, there are no reports available on genotype-controlled matches among different altitude-adapted indigenous populations.Objective: To explore the possible differences in plasma lipid profile and cardiovascular risk among autochthonous Kiwcha people inhabitants of low and high-altitude locations.Methodology: A cross-sectional analysis of plasmatic lipid profiles and cardiovascular risk factors in lowland Kiwchas from Limoncocha (230 m) and high-altitude Kiwchas from Oyacachi (3,800 m).Results: In the low altitude group, 66% were women (n = 78) and 34% (n = 40) were men, whereas in the high altitude group, 59% (n = 56) were women and 41% (n = 41%) were men. We found the proportion of overweight and obese individuals to be higher among low altitude dwellers (p < 0.05). Red blood cells (RBCs), hemoglobin concentration, and SpO2% were higher among high altitude dwellers and the erythrocyte size was found to be smaller at high altitude. The group located at low altitude also showed lower levels of plasma cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL), but most of these differences are not influenced by gender or elevation.Conclusions: Living at an altitude elicits well-known adaptive physiological changes such as erythrocyte count, hemoglobin concentration, hematocrit level, and serum glucose level. We also report clinical differences in the plasma lipid profile, with higher levels of cholesterol, HDL, and LDL in inhabitants of the Andes Mountain vs. their Amazonian basin peers. Despite this, we did not find significant differences in cardiovascular risk.

Clinical Characteristics of Lipid Metabolism in Untreated Patients with Anti-MDA5 Antibody-Positive.

ObjectiveClinical characterization of lipid metabolism in untreated patients with anti-melanoma differentiation-associated gene 5 antibodies-positive (anti-MDA5+).MethodsBody-mass index (BMI), autoantibodies, lipid levels, and serum ferritin levels in 57 anti-MDA5+ patients were determined in the Department of Rheumatology and Immunology of the Second Affiliated Hospital of Chongqing Medical University.ResultsPlasma high-density lipoprotein (HDL) and apolipoprotein A1 (ApoA1) levels were significantly lower in deceased group than in the survival group (P < 0.05). Plasma levels of HDL and ApoA1 were significantly lower in patients who were simultaneously anti-MDA5+ and anti-Ro-52+ than in patients who were anti-MDA5+ alone (P < 0.05). Plasma levels of total cholesterol, low-density lipoprotein, HDL, and ApoA1 were significantly decreased in patients with high levels of serum ferritin compared with patients with low levels (P < 0.05). There were no significant differences in blood lipid levels between patients grouped according to BMI.Conclusion1) HDL and ApoA1 levels are important indicators of poor prognosis in anti-MDA5+ patients; 2) Dysregulated lipid metabolism in anti-MDA5+ patients is closely associated with anti-Ro-52 antibody and ferritin levels but independent of BMI; 3) HDL involvement in inflammation and immune regulation merits close attention by rheumatologists.

The Effect of Exercise Training on Serum Glucose and Lipid Profiles in Patients With Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Despite several studies on the effects of exercise training on glucose and lipid profiles in patients with breast cancer, no earlier study has systematically summarized their findings. Current systematic review and meta-analysis have been done on earlier clinical trials in this topic. Relevant studies published up to May 2020 were searched through PubMed, SCOPUS, and Google Scholar using predefined keywords. Studies that examined the effect of exercise training on serum glucose and lipid profiles in adult women with breast cancer were included. A total of 16 studies were included. Combining 10 effect sizes, exercise training had no significant influence on serum fasting plasma glucose concentrations (weighted mean difference [WMD] = 4.87; 95% confidence interval [CI], -4.65 to 14.29). However, it resulted in significant reduction of serum insulin (WMD = -2.37; 95% CI, -3.57 to -1.16) and homeostatic model assessment for insulin resistance (WMD = -0.71; 95% CI, -1.27 to -0.15) in 14 and 8 studies, respectively. Pooling 6 effect sizes, exercise training did not change serum total cholesterol (WMD = -11.99; 95% CI, -32.42 to 8.45), low-density lipoprotein (WMD = -3.21; 95% CI, -10.45 to 4.04), high-density lipoprotein (WMD = 4.13; 95% CI, -6.20 to 14.46), and triglyceride (WMD = -23.34; 95% CI, -66.96 to 20.29) concentrations. Subgroup analyses showed beneficial effects of exercise training on outcomes of interest among studies with higher methodological quality. Current meta-analysis demonstrated significant reductions in serum levels of insulin and insulin resistance following exercise training. However, exercise training had no significant effect on serum levels of fasting plasma glucose, total cholesterol, triglyceride, high-density lipoprotein, and low-density lipoprotein. Further high-quality studies are needed to shed light on this issue.

Correction of Familial LCAT Deficiency by AAV-hLCAT Prevents Renal Injury and Atherosclerosis in Hamsters-Brief Report.

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High-Density Lipoproteins and the Kidney.

Dyslipidemia is a typical trait of patients with chronic kidney disease (CKD) and it is typically characterized by reduced high-density lipoprotein (HDL)-cholesterol(c) levels. The low HDL-c concentration is the only lipid alteration associated with the progression of renal disease in mild-to-moderate CKD patients. Plasma HDL levels are not only reduced but also characterized by alterations in composition and structure, which are responsible for the loss of atheroprotective functions, like the ability to promote cholesterol efflux from peripheral cells and antioxidant and anti-inflammatory proprieties. The interconnection between HDL and renal function is confirmed by the fact that genetic HDL defects can lead to kidney disease; in fact, mutations in apoA-I, apoE, apoL, and lecithin–cholesterol acyltransferase (LCAT) are associated with the development of renal damage. Genetic LCAT deficiency is the most emblematic case and represents a unique tool to evaluate the impact of alterations in the HDL system on the progression of renal disease. Lipid abnormalities detected in LCAT-deficient carriers mirror the ones observed in CKD patients, which indeed present an acquired LCAT deficiency. In this context, circulating LCAT levels predict CKD progression in individuals at early stages of renal dysfunction and in the general population. This review summarizes the main alterations of HDL in CKD, focusing on the latest update of acquired and genetic LCAT defects associated with the progression of renal disease.

Dapagliflozin elevates plasma high-density lipoprotein levels and influences visceral fat gene expression in streptozotocin-induced diabetes mellitus.

Dapagliflozin (Dapa) could potentially be used to treat type 1 diabetes mellitus. We tested the hypothesis that it would influence blood lipid levels and visceral fat accumulation in a rodent diabetic model. We used three groups of male Wistar rats: Controls, streptozotocin (STZ)-treated rats and STZ-treated orally with Dapa (STZ+Dapa), 10 mg/kg/day for six weeks. Blood glucose and serum lipids levels were determined. Plasma levels of lipases (hormone-sensitive lipase, HSL and lipoprotein lipase, LPL), adipokines (leptin and adiponectin) and proinflammatory cytokines [tumour necrosis factor-alpha (TNFα) and interleukin-6 (IL-6)] were determined by ELISA assays. mRNA levels in the perirenal fat were determined by real-time PCR. Dapa suppressed STZ-related hyperglycemia by 20% (P < 0.05) and increased serum HDL when compared to the controls and the STZ-only treated rats (both P < 0.05). STZ treatment caused elevations of other serum lipids that were resistant to Dapa treatment. Dapa treatment also increased both plasma and visceral fat mRNA levels of leptin, LPL and IL-6, while decreasing plasma and fat expressions of HSL and TNFα compared to the STZ-only treated rats (all P < 0.05). Our results suggest that Dapa, in addition to its antidiabetic effect, also influences the function of adipose tissue which could be beneficial in the treatment of diabetes.

Development of a novel, sensitive translational immunoassay to detect plasma glial fibrillary acidic protein (GFAP) after murine traumatic brain injury

BackgroundGlial fibrillary acidic protein (GFAP) has emerged as a promising fluid biomarker for several neurological indications including traumatic brain injury (TBI), a leading cause of death and disability worldwide. In humans, serum or plasma GFAP levels can predict brain abnormalities including hemorrhage on computed tomography (CT) scans and magnetic resonance imaging (MRI). However, assays to quantify plasma or serum GFAP in preclinical models are not yet available.MethodsWe developed and validated a novel sensitive GFAP immunoassay assay for mouse plasma on the Meso Scale Discovery immunoassay platform and validated assay performance for robustness, precision, limits of quantification, dilutional linearity, parallelism, recovery, stability, selectivity, and pre-analytical factors. To provide proof-of-concept data for this assay as a translational research tool for TBI and Alzheimer’s disease (AD), plasma GFAP was measured in mice exposed to TBI using the Closed Head Impact Model of Engineered Rotational Acceleration (CHIMERA) model and in APP/PS1 mice with normal or reduced levels of plasma high-density lipoprotein (HDL).ResultsWe performed a partial validation of our novel assay and found its performance by the parameters studied was similar to assays used to quantify human GFAP in clinical neurotrauma blood specimens and to assays used to measure murine GFAP in tissues. Specifically, we demonstrated an intra-assay CV of 5.0%, an inter-assay CV of 7.2%, a lower limit of detection (LLOD) of 9.0 pg/mL, a lower limit of quantification (LLOQ) of 24.8 pg/mL, an upper limit of quantification (ULOQ) of at least 16,533.9 pg/mL, dilution linearity of calibrators from 20 to 200,000 pg/mL with 90–123% recovery, dilution linearity of plasma specimens up to 32-fold with 96–112% recovery, spike recovery of 67–100%, and excellent analyte stability in specimens exposed to up to 7 freeze-thaw cycles, 168 h at 4 °C, 24 h at room temperature (RT), or 30 days at − 20 °C. We also observed elevated plasma GFAP in mice 6 h after TBI and in aged APP/PS1 mice with plasma HDL deficiency. This assay also detects GFAP in serum.ConclusionsThis novel assay is a valuable translational tool that may help to provide insights into the mechanistic pathophysiology of TBI and AD.

Evaluation of the ameliorative effect of Spirulina (Arthrospira platensis) supplementation on parameters relating to lead poisoning and obesity in C57BL/6J mice

• Oral exposure of Spirulina to C57BL/6J mice with lead acetate and high-fat diet. • Lead-related anemia was normalized and hematocrit and ALAD activity were recovered. • Decrease of epididymal white adipose tissue and increase of HDL-C by Spirulina. • Mitigative effects of Spirulina on lead poisoning and obesity were suggested. The current study aimed to validate the possible ameliorative effects of Spirulina ( Arthrospira platensis ) on lead poisoning and obesity using C57BL/6J mice. After a treatment period, we performed metal analyses, as well as hematocrit and plasma biochemical parameter measurements, and assayed oxidative stress markers and erythrocyte δ-aminolevulinic acid dehydratase (ALAD) activity. Our results highlighted the effectiveness of Spirulina in improving anemia status with the normalization of hematocrit levels and ALAD activity ratios, even in mice that exhibited obesity in addition to lead poisoning. Spirulina treatment also decreased epididymal white adipose tissue weight and increased plasma high-density lipoprotein levels, which are normally reduced after lead exposure. However, most of the studied plasma biochemical parameters and oxidative stress markers did not show large changes after treatment, likely because of the short duration of treatment. Further studies with longer-term exposures are required to validate the usefulness of Spirulina suggested in the present study.

The Presence of Cholesteryl Ester Transfer Protein (CETP) in Endothelial Cells Generates Vascular Oxidative Stress and Endothelial Dysfunction.

Endothelial dysfunction precedes atherosclerosis and is an independent predictor of cardiovascular events. Cholesterol levels and oxidative stress are key contributors to endothelial damage, whereas high levels of plasma high-density lipoproteins (HDL) could prevent it. Cholesteryl ester transfer protein (CETP) is one of the most potent endogenous negative regulators of HDL-cholesterol. However, whether and to what degree CETP expression impacts endothelial function, and the molecular mechanisms underlying the vascular effects of CETP on endothelial cells, have not been addressed. Acetylcholine-induced endothelium-dependent relaxation of aortic rings was impaired in human CETP-expressing transgenic mice, compared to their non-transgenic littermates. However, endothelial nitric oxide synthase (eNOS) activation was enhanced. The generation of superoxide and hydrogen peroxide was increased in aortas from CETP transgenic mice, while silencing CETP in cultured human aortic endothelial cells effectively decreased oxidative stress promoted by all major sources of ROS: mitochondria and NOX2. The endoplasmic reticulum stress markers, known as GADD153, PERK, and ARF6, and unfolded protein response effectors, were also diminished. Silencing CETP reduced endothelial tumor necrosis factor (TNF) α levels, intercellular cell adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) expression, diminishing monocyte adhesion. These results support the notion that CETP expression negatively impacts endothelial cell function, revealing a new mechanism that might contribute to atherosclerosis.

Improvement of Postprandial Lipid Metabolism After Ileal Transposition in Non-obese Diabetic Rats.

Ileal transposition (IT) could reduce obesity and improve type 2 diabetes mellitus (T2DM). The main aim of our study was to investigate lipid metabolism changes in T2DM rats after IT without a weight reduction effect. Thirty male diabetic rats were randomly divided into IT, sham IT (SI), and control groups. The levels of plasma cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TGs), and bile acid were measured. After sacrifice, the white adipose tissue, brown adipose tissue and liver were weighed. IT induced significant improvement in glucose and lipid metabolism. There were no significant differences in the levels of cholesterol (P = 0.87), HDL (P = 0.70), LDL (P = 0.96), or TGs (P = 0.97) among the groups before surgery. After IT, the levels of cholesterol (P = 0.019), LDL (P = 0.004), and TGs (P < 0.001) were lower than those in the SI and control groups, while the level of HDL was not significantly different compared to those of the other groups (P = 0.437). Higher bile acid level (P = 0.001), lower white adipose tissue/total body weight ratio (P < 0.001), and lower liver/total body weight ratio (P = 0.003) were found in the IT group. The BAT/total body weight ratio in the IT group was higher than that in the SI or control groups (P = 0.002). IT could improve lipid metabolism in diabetic rats.

Prevalence of Metabolic Syndrome and its Components in Kanifing Municipality, The Gambia.

Background:Metabolic syndrome (MetS) is a complex syndrome with clustering of interrelated risk factors for cardiovascular disease and diabetes. Its rising worldwide prevalence has been largely related to the increasing obesity. In The Gambia, the last and only time a MetS related study was conducted, and then reported, was 21 years. Therefore, there is need for evaluating the prevalence of MetS and its components in the country.Objective:This study was aimed to evaluate the prevalence of MetS and its individual components in Kanifing Municipality (KM).Methods:It was a cross-sectional study conducted at Kanifing General Hospital, Kanifing Municipality. Data obtained from each participants included anthropometric indices, blood pressure, fasting plasma glucose, triglyceride and high-density lipoprotein levels, and clinical information.Results:One hundred and thirty-six participants were included in the analysis. The overall MetS prevalence was 54.4% with significant female predominance (female, 58%; male, 29.4%; P=0.025). The most predominant component among the study population was central obesity (raised WC) (72.8%). Hypertriglyceridemia was found to be the strongest predictor of MetS among our participants (OR: 118.13; 95% CI: 33.79-412.77; P < 0.001).Conclusion:Our study discloses a very high prevalence of MetS among the participants, and a significant female predominance, with central obesity the commonest Mets component. The results suggest that hypertriglyceridemia is the strongest predictor of metabolic syndrome in our study participants.

Testosterone aggravates cerebral vascular injury by reducing plasma HDL levels.

Testosterone is often used to improve the physiological function. But increased testosterone levels affect blood lipids and cause inflammation and oxidative stress, which are risk factors for vascular diseases. This study aimed at investigating the effects of testosterone on cerebral vascular injury using an established intracranial aneurysm (IA) model. Sixteen-week-old female C57Bl/6 mice were subcutaneously infused with testosterone propionate (TP; 5 mg/kg day) or plain soybean oil (controls) for 6 weeks. After 2 weeks of treatment, mice were given angiotensin II-elastase for another 4 weeks. The results showed that TP significantly increased cell apoptosis and reactive oxygen species production in cerebral artery, together with increases in plasma tumor necrosis factor-α (TNF-α) levels and in urinary 8-isoprostane levels. Plasma assays showed that 2 weeks after TP or soybean oil administration, the high-density lipoprotein (HDL) level was higher in the TP group than in controls. In vitro studies showed that testosterone increased TNF-α and monocyte chemotactic protein-1 mRNA and protein expression levels in RAW 264.7 macrophages. In summary, by reducing the HDL level, TP aggravates cerebral artery injury by increasing cell apoptosis, inflammation, and oxidative stress.

The effects of peripheral lipoprotein metabolism on cerebrovascular inflammation in APP/PS1 mice

AbstractBackgroundAlthough Alzheimer’s disease (AD) is characterized by amyloid beta (Aβ) plaques and neurofibrillary tangles, most AD patients also exhibit cerebrovascular dysfunction. Therefore, strategies promoting cerebrovascular resilience have potential as therapeutic or preventative interventions against AD. High‐density lipoproteins (HDL) have several known beneficial functions on peripheral vessels. Further, increased plasma HDL concentrations have been associated with reduced dementia risk and HDL supplementation reduces both amyloid pathology and cognitive deficits in AD model mice. We therefore hypothesized that HDL may promote cerebrovascular health to protect against AD. We investigated the effects of HDL specifically on the cerebrovasculature in APP/PS1 mice, an AD model, using two methods.MethodsFirst, we reduced plasma HDL levels by creating APP/PS1 mice genetically deficient for apolipoprotein (apo)A‐I, the primary protein component of HDL. Second, we treated 12‐month old APP/PS1 mice with a non‐brain penetrant liver X receptor (LXR) agonist for seven days to selectively upregulate the HDL biogenesis pathways in peripheral tissues. We measured cognitive deficits using cued and contextual fear conditioning tests. Fluorescent amyloid staining was used to assess vascular amyloid deposition. Immunofluorescent imaging evaluating glial fibrillary acidic protein (GFAP) and intercellular adhesion molecule 1 (ICAM‐1) association with CD31 positive area was used to assess vessel‐associated astrogliosis and endothelial inflammation, respectively.ResultsAt 12 months of age, apoAI‐null mice had increased cognitive deficits in cued and contextual fear conditioning tests, increased vascular amyloid burden, increased vessel‐associated astrogliosis, and increased brain endothelial cell inflammation. Seven days of LXR agonist treatment had no effect on amyloid pathology or astrogliosis. However, LXR agonist‐treated APP/PS1 mice displayed reduced cognitive deficits in cued fear conditioning tests and reduced endothelial cell inflammation.ConclusionsCirculating HDL promotes cerebrovascular health in APP/PS1 mice by limiting both Aβ‐induced vascular inflammation and vascular Aβ deposition resulting in reduced amyloid pathology and cognitive deficits.

Prevalence, combinations and associations of components of MetS among adults aged 40 years and above from rural Kerala: a cross-sectional study

Background: Metabolic syndrome (MetS) is a growing public health concern worldwide. A nation-wide diabetes screening campaign by the union health ministry found rural areas of selected district of Kerala had16% prevalence of lifestyle diseases. One of the objectives of WHO developed action plan for global implementation of strategies in prevention and control of non-communicable diseases (NCDs) advocates identifying MetS, a simple clinical tool, for predicting diabetes mellitus and cardiovascular diseases among population. The study aimed to estimate the prevalence of metabolic syndrome and its components among the adults aged 40 and above from rural Kerala and to determine the association with socio-demographic characteristics like co-variables of the study population.Methods: A cross-sectional study conducted among adult subjects aged 40 and above from rural field practice areas visiting RHTC. Socio-demographic profile, personal habits and history on NCDs recorded. Blood pressure and abdominal circumference measured. Fasting plasma glucose (FPG), triglyceride (TG), and high-density lipoprotein (HDL) levels were estimated. Modified NCEP-ATP III (SAS), 2009 criteria was used to diagnose MetS. Study variables were analysed for associations and comparison of means with appropriate statistical methods.Results: The prevalence of metabolic syndrome (MetS) was 29.3%. 57.9% elevated FPG, 37% Triglyceridemia, 24% sub-optimal HDL, 38.3% abdominal obesity, 38.3% elevated BP, 52% insulin resistance were recorded. Among MetS subjects 50% were in 50-59 years age group and MetS had statistically significant association with age (p value 0.005).Conclusions: Moderate prevalence of metabolic syndrome among rural subjects needs strengthening health education and screening services on NCDs.

Prolonged bedrest reduces plasma high-density lipoprotein levels linked to markedly suppressed cholesterol efflux capacity

Recent observations strongly connect high-density lipoproteins (HDL) function and levels with coronary heart disease outcomes and risk for infections and sepsis. To date, our knowledge of factors determining this connection is still very limited. The immobility associated with prolonged bedrest is detrimental to health, affecting several systems, including the cardiovascular, pulmonary, gastrointestinal, musculoskeletal and urinary. Effects of prolonged bedrest on the composition and functional properties of HDL remain elusive. We evaluated metrics of HDL composition and function in healthy male volunteers participating in a randomized, crossover head-down bedrest study. We observed that HDL cholesterol efflux capacity was profoundly decreased during bedrest, mediated by a bedrest associated reduction in plasma levels of HDL-cholesterol and major apolipoproteins (apo) apoA-I and apoA-II. Paraoxonase activity, plasma anti-oxidative capacity and the activities of lecithin-cholesterol acyltransferase and cholesteryl ester transfer protein were not affected. No change was observed in the content of HDL-associated serum amyloid A, a sensitive marker of inflammation. Resistive vibration exercise countermeasure during bedrest did not correct impaired cholesterol efflux capacity and only tended to increase arylesterase activity of HDL-associated paraoxonase. In conclusion, prolonged bedrest reduces plasma HDL levels linked to markedly suppressed HDL cholesterol efflux capacity. Resistive vibration exercise during bedrest did not correct HDL levels and impaired cholesterol efflux capacity.