Atherosclerosis is a chronic inflammation in the arterial wall involving cells of the innate and adaptive immune system that is promoted by hyperlipidemia. In addition, the immune system can influence lipids and lipoprotein levels and cellular lipid homeostasis can influence the level and function of the immune cells. We will review the effects of manipulation of adaptive immune cells and immune cell products on lipids and lipoproteins, focusing mainly on studies performed in murine models of atherosclerosis. We also review how lipoproteins and cellular lipid levels, particularly cholesterol levels, influence the function of cells of the innate and adaptive immune systems. The overriding theme is that these interactions are driven by the need to provide the energy and membrane components for cell proliferation and migration, membrane expansion and other functions that are so important in the functioning of the immune cells.
The brain is the most lipid-rich organ in the body and, owing to the impermeable nature of the blood-brain barrier, lipid and lipoprotein metabolism within this organ is distinct from the rest of the body. Apolipoproteins play a well-established role in the transport and metabolism of lipids within the CNS; however, evidence is emerging that they also fulfill a number of functions that extend beyond lipid transport and are critical for healthy brain function. The importance of apolipoproteins in brain physiology is highlighted by genetic studies, where apolipoprotein gene polymorphisms have been identified as risk factors for several neurological diseases. Furthermore, the expression of brain apolipoproteins is significantly altered in several brain disorders. The purpose of this article is to provide an up-to-date assessment of the major apolipoproteins found in the brain (ApoE, ApoJ, ApoD and ApoA-I), covering their proposed roles and the factors influencing their level of expression. Particular emphasis is placed on associations with neurological and psychiatric disorders.
Background: Worldwide, the prevalence of the metabolic syndrome (MetS) is estimated to be 70% among those with type 2 diabetes mellitus (T2DM). T2DM and MetS are associated with abnormal liver enzyme levels, which can be the result of non-alcoholic fatty liver disease, cirrhosis, hepatocellular carcinoma or acute liver failure. The present study investigated the association between transaminases and MetS in T2DM patients. Methods: A descriptive cross-sectional study was conducted over the period of 6 months among 540 diabetic patients attending a tertiary care hospital in Nepal. The diagnosis of MetS was based on International Diabetes Federation (IDF), National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) and Harmonized definition 2009. Association between metabolic components and liver enzymes was established by crude and adjusted logistic regression analysis. Results: Overall, the prevalence of elevated enzyme levels was 58.9% for alanine aminotransferase (ALT), 42.2% for aspartate aminotransferase (AST) and 59.4% for gamma-glutamyl transferase (GGT). The presence of MetS was 23.3%, 36.1% and 51.9% according to NCEP ATP III, IDF and Harmonized criteria, respectively. In the binary logistic regression analysis, waist circumference > 102 cm (M) or > 88 cm (F) was only independently associated with all three elevated liver enzymes, odds ratio (OR) = 4.172 for ALT, OR = 2.795 for AST and OR = 0.245 for GGT. When all three criteria were entered for multivariate risk analysis, only the NCEP ATP III (+) was found to be associated independently with raised all three liver enzymes. Conclusion: Central obesity and MetS following NCEPATP III criteria were independently associated with elevated ALT, AST and GGT in our diabetic population. Clinicians may consider hepatic complication as a negligible component in T2DM. The present findings may encourage more attention.
Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are known to be anti-inflammatory and to alter gene expression within the cells. Emerging evidence indicates that one of the mechanisms for this process involves the alteration of epigenetic markers, such as DNA methylation. The focus of this overview is to document the current evidence for n-3 PUFA effects on DNA methylation and how these may impact on the inflammatory processes.
Background: Although several studies have assessed the association between thyroid hormones and dyslipidaemia, whether influencing thyroid function improves the lipid profile in euthyroid diabetic patients has not been studied. Methods: Fasting lipids were assessed in 11 euthyroid, treatment naive patients with type 2 diabetes (T2DM) and a micronodular texture of the thyroid gland (age: 43 ± 3.8 years, body mass index (BMI) 27.5 ± 1.4 kg/m 2 , triiodothyronine (T3) 119 ± 5.7 ng/dl, thyroxine (T4) 8.13 ± 0.46 μg/dl, thyroid- stimulating hormone (TSH) 1.51 ± 0.14 μIU/ml, free thyroxine (FT4) 1.272 ± 0.047 ng/dl) before and after administration of 50 μg of T4 once daily for 2 months. A placebo was given to 11 age, sex and BMI-matched euthyroid, treatment naive patients with T2DM. Care was taken to avoid even subclinical hyperthyroidism. Results: TSH fell significantly post-treatment (1.51 ± 0.11 vs. 0.79 ± 0.11 μIU/ml, p < 0.0001), but remained within the reference range. Total cholesterol (212 ± 21 vs. 158 ± 10 mg/dl, p = 0.003), low-density lipoprotein cholesterol (146 ± 17 vs. 112 ± 9 mg/dl, p = 0.007), high density lipoprotein cholesterol (51 ± 4 vs. 40 ± 3 mg/dl p = 0.001), triglycerides (93 ± 13 vs. 72 ± 8 mg/dl, p = 0.015), apolipoprotein A1 (167 ± 15 vs. 127 ± 8 mg/dl, p = 0.004), apolipoprotein B (101 ± 13 vs. 72 ± 7 mg/dl, p = 0.009) and lipoprotein (a) (60 ± 15 vs. 41 ± 11 mg/dl p = 0.009) all fell significantly after T4 administration for 2 months. No changes were observed in the placebo group. Conclusions: Small doses of T4 administered to euthyroid patients with T2DM significantly improved lipid levels. This could contribute to a reduced risk of macrovascular complications.
These Lipid Association of India (LAI) recommendations refer to specific patient populations. They follow the previously published LAI part 1 recommendations. These part 2 LAI recommendations focus on specific patient groups. These include patients with heart failure, chronic kidney disease, non-alcoholic fatty liver disease, cerebrovascular disease, thyroid disorders, inflammatory joint diseases, familial hypercholesterolaemia and human immunodeficiency virus infection. We also consider women, the elderly and post-transplantation patients. The current recommendations are based, as much as possible, on available data from Indian populations.
Background: The prevalence of non-alcoholic fatty liver disease (NAFLD) among Indian Asians in high-income countries is not well studied, but appears to be different from that for Western populations. Design: Cross-sectional study of subjects recruited through a community cardiovascular (CV) screening programme at two London Hindu temples from 2010-2012. NAFLD was diagnosed using the fatty liver index (FLI) and fibrosis stage through the BARD (Body Mass Index (BMI), Aspartate aminotransferase to Alanine aminotransferase ratio and Diabetes Mellitus) score. Results: 597 subjects were assessed; 306 (51%) female. Median (interquartile range) age and BMI were 49 (40.6-55.0) years and 26.4 (23.5-29.2) kg/m 2 , respectively. NAFLD was diagnosed in 184 (30.8%) cases, but 175 (29.3%) subjects could not be categorised. Overall, 117 (40.2%) men and 67 (21.9%) women had evidence of NAFLD (p < 0.001). In those with evidence of NAFLD, 142 (78.5%) had a BARD score suggestive of advanced fibrosis. Advanced fibrosis could be excluded in 5 (7.6%) women and 34 (29.6%) men (p < 0.001). Total cholesterol (TC), triglycerides (TG) and non-HDL (high-density lipoprotein cholesterol) were higher in the NAFLD group (p < 0.001), whereas HDL-C was lower (p < 0.001). Conclusion: There is evidence of a high prevalence of asymptomatic NAFLD, possibly in combination with advanced liver damage, among UK-based Gujarati Indians living in London. NAFLD is emerging as an independent risk factor for CV disease. Screening programmes should be developed in order to decrease liver and CV mortality and morbidity in these high-risk patients.
Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are chronic, immune-mediated diseases which may be associated with the presence of lipoprotein X (LpX). This is an abnormal lipoprotein resulting in marked elevation of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) concentration. LpX is rich in free cholesterol (FC) and phospholipids (PL) and low in esterified cholesterol (CE). We describe two cases with florid lipid stigmata and presence of LpX. A patient with PBC presented with itching and palmar xanthomata. TC = 55.5 mmol/L, direct LDL-C = 14.9 mmol/L, high-density lipoprotein cholesterol (HDL-C) = 0.5 mmol and triglycerides (TG) = 11.3 mmol/L. Lipoprotein electrophoresis (LPE) showed the presence of LpX. An apolipoprotein E (Apo E) phenotype and genotype reported E2E3 and E3E3 isoforms, respectively. A patient with PSC presented with itchy eruptive xanthomata. TC = 22.8 mmol/L, calculated LDL-C = 21.7 mmol/L, HDL-C = 0.2 mmol/L and TG = 1.6 mmol/L. LPE was normal. Both Apo E phenotype and genotype showed E2E3 isoforms. Both patients were treated with statins and showed resolution of lipid stigmata and improvement of lipid parameters, including PL, FC and LpX. In the first case, Apo E phenotype showed an E3E3 phenotype like the genotype following the decrease in LpX. LpX can interfere with other routine biochemical measurements, falsely increase TC and LDL-C levels and in our patient with PBC, we believe that LpX interfered with Apo E phenotype analysis. This has not been previously described.
Background: Combining statins with ezetimibe synergistically enhances lipid lowering, thereby reducing the need to prescribe maximal statin doses to achieve low-density lipoprotein cholesterol (LDL-C) goals. Real-world data on concurrent ezetimibe + statin therapy in Asians are sparse. Therefore, we evaluated the effectiveness of a single combined tablet of ezetimibe + simvastatin 10.0 + 20.0 mg (EZE + SIM) in Taiwanese patients with hypercholesterolaemia. Methods: We analysed retrospective data from patients who received EZE + SIM at a community hospital in New Taipei City, Taiwan, took EZE + SIM continuously for ≥24 weeks, and had before and after lipid data. Outcomes including lipid lowering, LDL-C goal attainment and safety (non-lipid serum biochemistry), were compared between diabetic versus non-diabetic patients and subgroups prescribed different EZE + SIM doses. Results: Among 157 EZE + SIM users, more than half had diabetes (64.3%) and/or hypertension (52%) and 24.1% had coronary artery disease. A mean EZE + SIM dose of 6.5 + 13.0 (median 5.0 + 10.0) mg/day for a mean of 51.6 weeks, significantly reduced total cholesterol (−30.4%), LDL-C (−36.2%) and triglycerides (−14.5%); consequently, attainment rates of LDL-C ≤ 100 mg/dl and ≤70 mg/dl goals were significantly higher after EZE + SIM treatment. There were no clinically significant changes in biomarkers of hepatic or renal function. Consistent with other reports, we observed indications of greater lipid-lowering efficacy and LDL-C goal attainment among patients with diabetes versus those without, at equivalent EZE + SIM doses. Conclusions: Our findings affirm the lipid-lowering efficacy of single-tablet fixed-dose EZE + SIM in real-world Taiwanese-Chinese patients with hypercholesterolaemia, especially at the recommended dose. Trends towards greater efficacy in diabetic than non-diabetic patients suggest that EZE + SIM may be a rational choice for treating patients with hypercholesterolaemia and diabetes.
Interleukin-6 (IL-6) is a unique pleiotropic cytokine exhibiting both pro- and anti-inflammatory properties depending on the target cell type. Plasma IL-6 levels are associated with cardiovascular risk. IL-6 elevation in atherosclerosis results in effects on multiple cells involved in lipid processing and plaque formation. IL-6 is also the primary determinant of acute phase protein production. IL-6 has a number of properties that foster development of cardiovascular disease. These include activation of endothelial cells, pro-thrombotic effects on platelets and promotion of smooth muscle proliferation and macrophage lipid accumulation. Despite these overall unfavourable effect on cells involved in atheroma formation, IL-6 also has a positive impact on the lipid handling system through upregulation of ATP binding cassette transporter (ABC)A1, a protein involved in macrophage lipid efflux. Further, IL-6 can inhibit other inflammatory cytokines. Based on its possible role in accelerating atherosclerosis, blockade of IL-6 action with the antibody tocalizumab, a treatment for rheumatoid arthritis and juvenile rheumatoid arthritis, has been evaluated as an atheroprotective agent, but studies are inconclusive. This review discusses multiple aspects of IL-6 effects on parameters related to development of atherosclerosis and highlights their manifestations in cell culture, murine models and human studies.
Oxysterols are metabolites of cholesterol that are produced in liver and other peripheral tissues as a means to eliminate cholesterol to bile acid. Recent studies have revealed that the most abundant circulating oxysterol 27-hydroxycholesterol (27HC) is the first identified endogenous selective estrogen receptor modulator. 27HC levels correlate well with that of cholesterol, and also rise progressively with age. 27HC affects estrogen receptor function by the antagonism of estrogen action and also by the direct modulation of the receptor function, and similar to estrogen/estrogen receptors, 27HC has many actions in various tissues. This review article introduces the recent progress in the understanding of the role of 27HC in breast cancer and cardiovascular dysfunction.
The presence of brown adipose tissue (BAT) in adult humans has been rediscovered through the clinical use of the radioactive glucose analog F-fluorodeoxyglucose with PET. This has led to numerous studies demonstrating cold exposure as the major physiological modulator of BAT activity. These reports also suggested that age, gender, BMI and the presence of diabetes are also important modulators of BAT volume and metabolic activity. Although F-fluorodeoxyglucose PET has provided important information on BAT glucose metabolism, other techniques are being developed and applied to assess other aspects of BAT metabolism. Here, we summarize the current understanding of the pathophysiological functions of BAT in humans and discuss some of the strengths and limitations of the current investigational techniques.
Diabetes is often associated with dyslipidemia, a main risk factor for cardiovascular diseases. According to the traditional recommendations and experimental studies, numerous phytochemicals have been suggested for dyslipidemia. In most cases, however, limited evidence exists regarding their clinical usefulness. This review focuses on phytochemicals that have been investigated in clinical trials, particularly their hypolipidemic actions in diabetic patients. Proposed mechanisms for the hypolipidemic effects of such phytochemicals and their potential side effects are discussed. According to the evidence currently available, , , , and have acquired enough reputation for treatment of diabetic dyslipidemia. These herbs have demonstrated hypolipidemic and in some cases hypoglycemic activity in diabetic patients. Therefore, their consumption may improve the management of dyslipidemia and reduce cardiovascular risk in diabetic patients.
Mitochondrial dysfunction is centrally involved in heart ischemia/reperfusion (I/R) injury. Increased reactive oxygen species production, impaired respiratory chain complexes activity and opening of the mitochondrial permeability transition pore have been suggested as possible factors responsible for mitochondrial dysfunction in heart I/R injury. Cardiolipin (CL), a phospholipid of the inner mitochondrial membrane, plays an important role in mitochondrial bioenergetics. CL alterations have been shown to play a causative role in mitochondrial dysfunction in a variety of pathological conditions, as well as in cell death. The role of CL alterations in mitochondrial dysfunction in heart I/R injury is here reviewed. Several cardioprotective strategies to prevent myocardial injury during I/R targeting mitochondrial CL are also examined.
The aim of this study was to test small dense LDL changes with Armolipid Plus treatment in patients with familial combined hyperlipidemia (FCHL). After 4 weeks, 30 patients with FCHL were included in an 8-week, randomized, double-blind study and were taking, in addition to the standard diet, either placebo or Armolipid Plus. The placebo group showed no statistically significant differences in the studied parameters; instead, in the Armolipid Plus group, statistically significant reduction differences were detected in BMI (p = 0.010), LDL score (p = 0.035) and an increase in mean LDL particle diameter (p = 0.040). The combination of a standard diet with Armolipid Plus is able to reduce LDL score and increase LDL particle diameter in a group of FCHL after 8 weeks of treatment.