Lipid Atherosclerosis Research Articles

Correlation of MicroRNA-125b, Sirtuin, and Signal Transducer and Activator of Transcription 3 with Biochemical Parameters and Risk Factors in Atherosclerosis Patients.

Atherosclerosis (AS) is an inflammatory disease linked to vascular events, with dysregulation of microRNA (miR)-125b, contributing to cardiovascular disease pathogenesis. Moreover, there is evidence of the involvement of signal transducer and activator of transcription 3 (STAT3) and sirtuin 6 (SIRT6) in AS. This study aimed to survey the expression levels of miR-125b, STAT3, and SIRT6 in the peripheral blood mononuclear cells (PBMCs) of AS patients and controls, and to find their correlations with biochemical parameters and risk factors. This study included blood samples from 45 controls and 45 AS patients, with PBMCs isolated using Ficoll solution. Expression levels of miR-125b, STAT3, and SIRT6 were determined via quantitative Real Time-PCR. The findings revealed a significant increase in miR-125b levels in patients compared to controls (P = 0.017). However, alterations in STAT3 and SIRT6 expression were not significant (P> 0.05). There was no substantial relationship between miR-125b and STAT3 (P = 0.522) or SIRT6 (P = 0.88). miR-125b showed a significant relationship with atherogenic indexes and creatinine (P<0.05), while the association of SIRT6 with HDL and creatinine was significant (P<0.05). STAT3 exhibited high diagnostic power for identifying individuals at risk of heart disease and hypertension (P<0.05). STAT3 can serve as a valuable biomarker for detecting AS and AS-related risk factors. miR-125b and SIRT6 may be associated with AS lipid metabolism. However, further studies with larger sample sizes are recommended to mechanistically elucidate the association of these genes.

Genetically predicted HLA-DR+ natural killer cells as potential mediators in the lipid-coronary artery disease/ calcification (CAD/CAC) causal pathway.

Coronary artery disease (CAD) imposes a significant global health burden, necessitating a deeper comprehension of its genetic foundations to uncover innovative therapeutic targets. Employing a comprehensive Mendelian randomization (MR) approach, we aimed to explore the genetic associations between lipid profiles, immune cell phenotypes, and CAD risk. Utilizing data from recent large-scale genome-wide association studies (GWAS), we scrutinized 179 lipid and 731 immune cell phenotypes to delineate their genetic contributions to CAD pathogenesis, including coronary artery calcification (CAC). Moreover, specific immune cell phenotypes were examined as potential mediators of the lipid-CAD/CAC causal pathway. Among the 162 lipid species with qualified instrumental variables (IVs) included in the analysis, we identified 36 lipids that exhibit a genetic causal relationship with CAD, with 29 being risk factors and 7 serving as protective factors. Phosphatidylethanolamine (18:0_20:4) with 8 IVs (OR, 95% CI, P-value: 1.04, 1.02-1.06, 1.50E-04) met the Bonferroni-corrected significance threshold (0.05/162=3.09E-04). Notably, all 18 shared lipids were determined to be risk factors for both CAD and CAC, including 16 triacylglycerol traits (15 of which had ≥ 3 IVs), with (50:1) exhibiting the highest risk [OR (95% CI) in CAC: 1.428 (1.129-1.807); OR (95% CI) in CAD: 1.119 (1.046-1.198)], and 2 diacylglycerol traits. Furthermore, we identified HLA DR+ natural killer cells (IVs = 3) as nominally significant with lipids and as potential mediators in the causal pathway between diacylglycerol (16:1_18:1) or various triacylglycerols and CAD (mediated effect: 0.007 to 0.013). This study provides preliminary insights into the genetic correlations between lipid metabolism, immune cell dynamics, and CAD susceptibility, highlighting the potential involvement of natural killer cells in the lipid-CAD/CAC causal pathway and suggesting new targets for therapy. Further evidence is necessary to substantiate our findings.

Elucidation of the anti-β-cell dedifferentiation mechanism of a modified Da Chaihu Decoction by an integrative approach of network pharmacology and experimental verification

Ethnopharmacological relevanceModified Da Chaihu decoction (MDCH) is a traditional Chinese herbal prescription that has been used in the clinic to treat type 2 diabetes (T2D). Previous studies have confirmed that MDCH improves glycemic and lipid metabolism, enhances pancreatic function, and alleviates insulin resistance in patients with T2D and diabetic rats. Evidence has demonstrated that MDCH protects pancreatic β cells via regulating the gene expression of sirtuin 1 (SIRT1) and forkhead box protein O1 (FOXO1). However, the detailed mechanism remains unclear. Aim of the studyDedifferentiation of pancreatic β cells mediated by FOXO1 has been recognized as the main pathogenesis of T2D. This study aims to investigate the therapeutic effects of MDCH on T2D in vitro and in vivo to elucidate the potential molecular mechanisms. Materials and methodsTo predict the key targets of MDCH in treating T2D, network pharmacology methods were used. A T2D model was induced in diet-induced obese (DIO) C57BL/6 mice with a single intraperitoneal injection of streptozotocin. Glucose metabolism indicators (oral glucose tolerance test, insulin tolerance test), lipid metabolism indicators (total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol), inflammatory factors (C-reactive protein, interleukin 6, tumor necrosis factor alpha), oxidative stress indicators (total antioxidant capacity, superoxide dismutase, malondialdehyde), and hematoxylin and eosin staining were analyzed to evaluate the therapeutic effect of MDCH on T2D. Immunofluorescence staining and quantification of FOXO1, pancreatic and duodenal homeobox 1 (PDX1), NK6 homeobox 1 (NKX6.1), octamer-binding protein 4 (OCT4), neurogenin 3 (Ngn3), insulin, and SIRT1, and Western blot analysis of insulin, SIRT1, and FOXO1 were performed to investigate the mechanism by which MDCH inhibited pancreatic β-cell dedifferentiation. ResultsThe chemical ingredients identified in MDCH were predicted to be important for signaling pathways related to lipid metabolism and insulin resistance, including lipids in atherosclerosis, the advanced glycation end product receptor of the advanced glycation end product signaling pathway, and the FOXO signaling pathway. Experimental studies showed that MDCH improved glucose and lipid metabolism in T2D mice, alleviated inflammation and oxidative stress damage, and reduced pancreatic pathological damage. Furthermore, MDCH upregulated the expression levels of SIRT1, FOXO1, PDX1, and NKX6.1, while downregulating the expression levels of OCT4 and Ngn3, which indicated that MDCH inhibited pancreatic dedifferentiation of β cells. ConclusionsMDCH has therapeutic effects on T2D, through regulating the SIRT1/FOXO1 signaling pathway to inhibit pancreatic β-cell dedifferentiation, which has not been reported previously.

Identifying lipid traces of atherogenic mechanisms in human carotid plaque

Background and aimsLipids play an important role in atherosclerotic plaque development and are interesting candidate predictive biomarkers. However, the link between circulating lipids, accumulating lipids in the vessel wall, and plaque destabilization processes in humans remains largely unknown. This study aims to provide new insights into the role of lipids in atherosclerosis using lipidomics and mass spectrometry imaging to investigate lipid signatures in advanced human carotid plaque and plasma samples. MethodsWe used lipidomics and desorption electrospray ionization mass spectrometry imaging (DESI-MSI) to investigate lipid signatures of advanced human carotid plaque and plasma obtained from patients who underwent carotid endarterectomy (n = 14 out of 17 whose plaque samples were analyzed by DESI-MSI). Multivariate data analysis and unsupervised clustering were applied to identify lipids that were the most discriminative species between different patterns in plaque and plasma. These patterns were interpreted by quantitative comparison with conventional histology. ResultsLipidomics detected more than 300 lipid species in plasma and plaque, with markedly different relative abundances. DESI-MSI visualized the spatial distribution of 611 lipid-related m/z features in plaques, of which 330 m/z features could be assigned based on exact mass, comparison to the lipidomic data, and high mass resolution MSI. Matching spatial lipid patterns to histological areas of interest revealed several molecular species that were colocalized with pertinent disease processes in plaque including specific sphingomyelin and ceramide species with calcification, phospholipids and free fatty acids with inflammation, and triacylglycerols and phosphatidylinositols with fibrin-rich areas. ConclusionsBy comparing lipid species in plaque and plasma, we identified those circulating species that were also prominently present in plaque. Quantitative comparison of lipid spectral patterns with histology revealed the presence of specific lipid species in destabilized plaque areas, corroborating previous in vitro and animal studies.

Unraveling the Role of Scutellaria baicalensis for the Treatment of Breast Cancer Using Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation.

Scutellaria baicalensis is often used to treat breast cancer, but the molecular mechanism behind the action is unclear. In this study, network pharmacology, molecular docking, and molecular dynamics simulation are combined to reveal the most active compound in Scutellaria baicalensis and to explore the interaction between the compound molecule and the target protein in the treatment of breast cancer. In total, 25 active compounds and 91 targets were screened out, mainly enriched in lipids in atherosclerosis, the AGE-RAGE signal pathway of diabetes complications, human cytomegalovirus infection, Kaposi-sarcoma-associated herpesvirus infection, the IL-17 signaling pathway, small-cell lung cancer, measles, proteoglycans in cancer, human immunodeficiency virus 1 infection, and hepatitis B. Molecular docking shows that the two most active compounds, i.e., stigmasterol and coptisine, could bind well to the target AKT1. According to the MD simulations, the coptisine-AKT1 complex shows higher conformational stability and lower interaction energy than the stigmasterol-AKT1 complex. On the one hand, our study demonstrates that Scutellaria baicalensis has the characteristics of multicomponent and multitarget synergistic effects in the treatment of breast cancer. On the other hand, we suggest that the best effective compound is coptisine targeting AKT1, which can provide a theoretical basis for the further study of the drug-like active compounds and offer molecular mechanisms behind their roles in the treatment of breast cancer.

Lipids in Atherosclerosis: Pathophysiology and the Role of Calculated Lipid Indices in Assessing Cardiovascular Risk in Patients with Hyperlipidemia

The role of lipids is essential in any phase of the atherosclerotic process, which is considered a chronic lipid-related and inflammatory condition. The traditional lipid profile (including the evaluation of total cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein) is a well-established tool to assess the risk of atherosclerosis and as such has been widely used as a pillar of cardiovascular disease prevention and as a target of pharmacological treatments in clinical practice over the last decades. However, other non-traditional lipids have emerged as possible alternative predictors of cardiometabolic risk in addition to traditional single or panel lipids, as they better reflect the overall interaction between lipid/lipoprotein fractions. Therefore, this review deals with the lipid involvement characterizing the pathophysiology of atherosclerosis, discussing some recently proposed non-traditional lipid indices and, in the light of available knowledge, their actual potential as new additive tools to better stratify cardiovascular risk in patients with hyperlipidemia as well as possible therapeutic targets in the clinical practice.

Identification of the Anti-Inflammatory Compound, Paeoniflorigenone, in Radix Paeoniae Alba for the Treatment of Polycystic Ovary Syndrome Through Network Pharmacology and Molecular Docking

Introduction: Polycystic ovary syndrome (PCOS) is a common endocrine disease that is characterized by chronic inflammation. Baishao (radix paeoniae alba, RPA), classified as a top-grade herbal medicine in TCM, has anti-inflammatory, immune adjustment, and anti-oxidative activities. RPA has been used to treat PCOS in clinical practice, but its potential mechanism of action is unclear. This study aimed at exploring the potential mechanism of RPA in PCOS treatment and to investigate the anti-inflammatory constituents of RPA. Methods: The TCMSP database was used to screen the potential active compounds of RPA. On the other hand, the possible target genes of PCOS were collected from the TTD, DrugBank, GeneCard, OMIM, and PharmGKB databases. The PPI network of RPA–PCOS target genes was established by STRING, and the visual network among RPA, ingredients, disease and potential target genes was constructed in Cytoscape. The bioactivity and potential mechanism of RPA in PCOS treatment were analyzed by GO and KEGG enrichment approaches. Furthermore, molecular docking was utilized to indicate the best compounds of RPA binding with TNF-α. Results: Fifty-four potential target genes were filtered and gathered from RPA and PCOS. Visual network indicated that 8 ingredients in RPA, β-sitosterol, ( + )-catechin, palbinone, sitosterol, mairin, kaempferol, paeoniflorigenone, and paeoniflorin, were closely correlated with 54 possible therapeutic target genes. The possible pathways relating the treatment of PCOS by RPA mainly contained the TNF, lipid atherosclerosis, C-type lectin receptor, and AGE-RAGE signal pathways. Paeoniflorigenone was the optimal anti-inflammatory compound of RPA to bind with TNF-α in molecular docking analysis. Conclusion: This study manifested that the most effective anti-inflammation compound of RPA was paeoniflorigenone and provided a potential therapeutic strategy for PCOS treatment.

Mendelian randomization of circulating proteome identifies actionable targets in heart failure

BackgroundHeart failure (HF) is a prevalent cause of mortality and morbidity. The molecular drivers of HF are still largely unknown.ResultsWe aimed to identify circulating proteins causally associated with HF by leveraging genome-wide genetic association data for HF including 47,309 cases and 930,014 controls. We performed two-sample Mendelian randomization (MR) with multiple cis instruments as well as network and enrichment analysis using data from blood protein quantitative trait loci (pQTL) (2,965 blood proteins) measured in 3,301 individuals. Nineteen blood proteins were causally associated with HF, were not subject to reverse causality and were enriched in ligand-receptor and glycosylation molecules. Network pathway analysis of the blood proteins showed enrichment in NF-kappa B, TGF beta, lipid in atherosclerosis and fluid shear stress. Cross-phenotype analysis of HF identified genetic overlap with cardiovascular drugs, myocardial infarction, parental longevity and low-density cholesterol. Multi-trait MR identified causal associations between HF-associated blood proteins and cardiovascular outcomes. Multivariable MR showed that association of BAG3, MIF and APOA5 with HF were mediated by the blood pressure and coronary artery disease. According to the directional effect and biological action, 7 blood proteins are targets of existing drugs or are tractable for the development of novel therapeutics. Among the pathways, sialyl Lewis x and the activin type II receptor are potential druggable candidates.ConclusionsIntegrative MR analyses of the blood proteins identified causally-associated proteins with HF and revealed pleiotropy of the blood proteome with cardiovascular risk factors. Some of the proteins or pathway related mechanisms could be targeted as novel treatment approach in HF.

ROS responsive nanoparticles loaded with lipid-specific AIEgen for atherosclerosis-targeted diagnosis and bifunctional therapy

Atherosclerosis, which is triggered by endothelial damage, progressive local inflammation and excessive lipid accumulation, is one of the most common cardiovascular diseases in recent years. Drug delivery systems have shown great potential for the accurate diagnosis and effective treatment of early atherosclerosis, but are accompanied by disadvantages such as poor stability, lack of active targeting and non-specific recognition capabilities, which still need to be further developed. In our work, a multifunctional nanoparticle (LFP/PCDPD) with reactive oxygen species (ROS) responsive drug release, lipid removal, and lipid-specific AIE fluorescence imaging was constructed. Cyclodextrin structure with lipid removal function and PMEMA blocks with ROS-response-mediated hydrophobic to hydrophilic conversion were simultaneously introduced into the structure of LFP/PCDPD to load the anti-inflammatory drug prednisolone (Pred) and lipid-specific AIEgen (LFP). The active targeting function of LFP/PCDPD was conferred by the high affinity of dextran to the vascular adhesion molecule-1 (VCAM-1) and CD44 receptor on the surface of broken endothelial cells. After intravenous injection into ApoE−/− mice, LFP/PCDPD actively enriched in the microenvironment of local ROS overexpression and rich lipids in atherosclerosis. Pred and LFP were released while lipids were removed, thus enabling proactive targeting of atherosclerosis and efficient “two-pronged” treatment.

The potential effects and mechanisms of hispidulin in the treatment of diabetic retinopathy based on network pharmacology

BackgroundDiabetic retinopathy (DR), one of the most common and severe microvascular complication of diabetes mellitus (DM), is mainly caused by diabetic metabolic disorder. So far, there is no effective treatment for DR. Eriocauli Flos, a traditional Chinese herb, has been used in treating the ophthalmic diseases including DR. However, the active ingredients and molecular mechanisms of Eriocauli Flos to treat diabetic retinopathy remain elusive.MethodsHere, the systems pharmacology model was developed via constructing network approach. 8 active components which were screened by oral bioavailability (OB ≥ 30%) and drug-likeness (DL ≥ 0.18) and 154 targets were selected from Eriocauli Flos through TCMSP database. Another 3593 targets related to DR were obtained from Genecards, OMIM, TTD, and Drugbank databases. The 103 intersecting targets of DR and Eriocauli Flos were obtained by Draw Venn Diagram. In addition, protein-protein interaction network was established from STRING database and the compound-target network was constructed by Cytoscape which screened top 12 core targets with cytoNCA module. Then the overlapping targets were analyzed by GO and KEGG enrichment. Moreover, two core targets were selected to perform molecular docking simulation. Subsequently, CCK8 assay, RT-PCR and Western blotting were applied to further reveal the mechanism of new candidate active component from Eriocauli Flos in high glucose-induced HRECs.ResultsThe results showed that the overlapping targets by GO analysis were enriched in cellular response to chemical stress, response to oxidative stress, response to reactive oxygen species, reactive oxygen species metabolic process and so on. Besides, the overlapping targets principally regulated pathways such as AGE-RAGE signaling pathway in diabetic complications, lipid atherosclerosis, fluid shear stress and atherosclerosis, and PI3K-Akt signaling pathway. Molecular docking exhibited that VEGFA and TNF-α, had good bindings to the great majority of compounds, especially the compound hispidulin. In vitro, hispidulin ameliorated high-glucose induced proliferation by down-regulating the expression of p-ERK, p-Akt, and VEGFA; meanwhile inhibited the mRNA levels of TNF-α.ConclusionsIn this study, through network pharmacology analysis and experimental validation, we found that hispidulin maybe has a potential targeted therapy effect for DR by decreasing the expression of p-Akt, p-ERK, and VEGFA, which resulted in ameliorating the proliferation in HRECs.

The impact of lipid in atherosclerosis and heart failure in the east of Algeria

In the east of Algeria, the rate of atherosclerosis is very high, unfortunately the pathological and radiology are not sufficient for evaluation and confirmation of the diagnosis. Today atherosclerosis is considered a complex pathology at the crossroads of lipid, oxidative and inflammatory alterations. Its development is caused by an immune response leading to the retention of cholesterol-rich lipoproteins in the arterial wall. Improving living conditions can have a negative influence on this pathology, such as a sedentary lifestyle, greater accessibility to a diet rich in fat, but it's not just that, there are also genetic factors. The objective of this study was to determine the impact of lipid in patients with atherosclerosis in Algerian patients and the influence of certain modifiable and non-modifiable risk factors. This is a prospective study that describes the epidemiological, diagnostic and therapeutic aspects in 50 patients, in the cardiology department of CHU Constantine during the year 2020-2021. The results of our study indicate that Atherosclerosis is frequent attack, which develops with age, behaviors related to healthy living risk factors for the disease may explain part of the cause These factors cause disturbances in the lipid profile (LDL-c and HDL-c levels and triglycerides); these in turn increase the risk of atherosclerosis. All subjects with atherosclerosis present with dyslipidemia; with very high LDL-c concentrations averaging 2.12g / l in men and 2.08g / l in women. Very high triglyceride levels on average 1.88g / l in men and 2.87g / l in women. Reduced HDL-c concentrations averaging 0.2g / l in both sexes and elevated total cholesterol concentrations averaging 3.6g / l averaging in men and 3.25g / l in women. There was a highly significant correlation between increased concentration of LDL cholesterol and HDL LDL triglycerides and the development of atherosclerosis.

Medical Management of Vascular Disease

Although surgeons may be able to bypass or open blocked arteries and replace aneurysms with minimally invasive surgery, patients continue to die from the other cardiovascular consequences of vascular disease. Surgeons must become more involved in the nonsurgical treatments of peripheral artery disease (PAD). A good understanding of the role of lipids in atherosclerosis is critical but surgeons must also recognize the threats of diabetes; smoking; hypertension; and hyperlipidemia on PAD. Treatments, including lifestyle modification, diet, exercise, and the influence of lipid-lowering agents is described. Medications that can alter PAD are described in detail and include statins; fibrates; niacin; bile acid sequestrants; ezetimibe; and antiplatelet agents. Side effects and monitoring is also described. Although much of the review covers the general principles of medical management of patients with PAD, components of this overall disease process are also provided and include pharmacological intervention for claudication; stroke; aortic aneurysms; and nonatherosclerotic vascular disease. This review contains 2 figures, 2 tables, and 181 references.

The Atherogenic Role of Circulating Modified Lipids in Atherosclerosis.

Lipid accumulation in the arterial wall is a crucial event in the development of atherosclerotic lesions. Circulating low-density lipoprotein (LDL) is the major source of lipids that accumulate in the atherosclerotic plaques. It was discovered that not all LDL is atherogenic. In the blood plasma of atherosclerotic patients, LDL particles are the subject of multiple enzymatic and non-enzymatic modifications that determine their atherogenicity. Desialylation is the primary and the most important atherogenic LDL modification followed by a cascade of other modifications that also increase blood atherogenicity. The enzyme trans-sialidase is responsible for the desialylation of LDL, therefore, its activity plays an important role in atherosclerosis development. Moreover, circulating modified LDL is associated with immune complexes that also have a strong atherogenic potential. Moreover, it was shown that antibodies to modified LDL are also atherogenic. The properties of modified LDL were described, and the strong evidence indicating that it is capable of inducing intracellular accumulation of lipids was presented. The accumulated evidence indicated that the molecular properties of modified LDL, including LDL-containing immune complexes can serve as the prognostic/diagnostic biomarkers and molecular targets for the development of anti-atherosclerotic drugs.

Spatial Distributions of Lipids in Atherosclerosis of Human Coronary Arteries Studied by Time-of-Flight Secondary Ion Mass Spectrometry

The accurate spatial distribution of various lipid species during atherogenesis has remained unexplored. Herein, we used time-of-flight secondary ion mass spectrometry (TOF-SIMS) to analyze the lipid distribution in human coronary artery cryosections. The images from the TOF-SIMS allowed visualization of ions derived from individual species of cholesterol esters, phospholipids, and triacylglycerols in the context of lesion characteristics and severity. In addition, cholesterol-containing crystal-like structures were seen in high-resolution images of advanced lesions. The ratio of cholesterol fragment ions (m/z 385:m/z 369) was found to differentiate unesterified cholesterol from cholesterol esters. This ratio changed during atherogenesis and in different areas of the lesions, reflecting differences in the accumulation of the two forms of cholesterol. Thus, atheromas were characterized by accumulation of cholesterol esters with apolipoprotein B near the intima-media border, whereas in the complicated lesions, unesterified cholesterol dominated in neovessel-containing areas enriched in glycophorin A. Interestingly, triacylglycerols were found in areas surrounding neovessels and lacking either form of cholesterol. The lipid composition of the tunica media reflected the alterations observed in the intimal lipids, yet being more subtle. The detailed molecular information obtained by TOF-SIMS revealed unanticipated differences in the type and composition of the accumulating lipids in different stages of atherogenesis, notably the spatial segregation of cholesterol and triglycerides in the advancing lesions.

Even mildly elevated TSH is associated with an atherogenic lipid profile in postmenopausal women with subclinical hypothyroidism

Postmenopausal women, a population with increased risk of atherosclerosis, also have an appreciable risk of subclinical hypothyroidism (SCH). The current study sought an association between serum thyrotropin (TSH), the biomarker of SCH and atherosclerosis lipid profile changes. A total of 45 postmenopausal women with SCH and 27 healthy women matched by age and body mass index were enrolled in this observational study. Serum lipid profiles and thyroid function were assessed. Compared with healthy controls, the serum levels of TC, TG, LDL-c and oxidized LDL (oxLDL) in SCH were increased by ∼22.8%, 29.6%, 30.5% and 23.2%, respectively. TSH was positively correlated with TC, LDL-c and oxLDL in all of the study subjects after adjusting for age and BMI. In particular, the positive correlation remained significant after adjusting for serum FT3 and FT4. When further stratified by TSH levels, both the subgroup of mildly elevated TSH (4.78–9.99 mU/L) and overtly elevated TSH (>10.00 mU/L) exhibited significantly higher serum levels of TC, TG, LDL-c and oxLDL compared to the normal TSH subgroup. Path analysis revealed that the total effects of TSH on TC (total effectsTC,TSH = 0.4323) included a significant direct effect (direct effectTC,TSH = 0.4932) and an indirect effect via an intermediary variable (FT3, FT4). Furthermore, TC exhibited a direct effect on LDL-c, as did LDL-c on oxLDL. In conclusion, even with a mild elevation of serum TSH, SCH is associated with atherogenic lipid profiles in postmenopausal women independent of thyroid hormones.

Implications of chemokines, chemokine receptors, and inflammatory lipids in atherosclerosis

Chemokines are a diverse group of molecules with important implications for the development of solid tissues and normal function of the immune system. However, change of the conditions for such a complex system can have important and dangerous consequences leading to diseases. The specific implications of the various chemokines in diseases have been elucidated in the last few years, prompting hope of manipulating this system for therapy or prevention of diseases. On the other hand, inflammatory lipids are biologically active molecules with crucial impacts on the function of various cell types, including immune cells in health and disease. Here, we describe how these lipids affect the chemokine system and how they interact with chemokines to shape chronic inflammation in the case of atherosclerosis.

Abstract 442: Correlates of the Triglyceride/HDL Cholesterol Ratio: The Very Large Database of Lipids (VLDL-4)

Background The Triglyceride/HDL Cholesterol Ratio (TG/HDL-C) is predictive of atherosclerosis and vascular disease risk. It is frequently elevated in the metabolic syndrome and diabetes and tracks with measures of insulin resistance. Methods We investigated the correlates of TG/HDL-C in 3,609 serial subjects of the 1,340,614 U.S. adults from the VLDL dataset who had apoB, hsCRP, serum insulin levels, hemoglobin A1C (A1C) measurements in addition to ultracentrifugation lipid measurement by VAP method (Atherotech, Birmingham, AL). A continuous LDL density parameter (LLDR) was calculated as the natural log of the ratio of dense to buoyant LDL-C subfractions. Remnant lipoprotein cholesterol (RLP-C) was defined as dense remnant VLDL3-C + IDL-C. TG/HDL-C was modeled using multiple linear regression. Results The strongest correlates of TG/HDL-C in model 1 were serum insulin, RLP-C, LLDR and Lp(a)-C with overall model r=0.801, adjusted r2=0.641, p&lt;0.001. Model 2 substituted dense VLDL3-C and IDL-C individually as independent variables in lieu of their sum, RLP-C; overall model r=0.855, adjusted r2=0.730, p&lt;0.001. IDL-C was inversely correlated while VLDL3-C was more strongly and positively associated with TG/HDL-C. A1C was not significantly correlated in the multivariate models (Table). Summary TG/HDL-C ratio represents a composite of metabolic and lipid atherosclerosis risk markers including insulin levels, LDL density, RLP-C, lp(a)-C, homocysteine, gender and apoB.

Unraveling the role of nicotinamide phosphoribosyltransferase on lipids in atherosclerosis

The role of nicotinamide phosphoribosyltransferase (NAMPT) in lipid metabolism and atherosclerosis is complex. Several reports support a role for NAMPT in atherogenesis. NAMPT is increased in atheroscleroticrelated diseases, such as obesity and Type 2 diabetes. NAMPT seems to include proatherogenic (e.g., enhancing effects on inflammation and matrix degradation) as well as antiatherogenic (e.g., antiapoptotic effects on monocytes/macrophages) effects. Recent studies suggest that NAMPT could also mediate atheroprotective effects on lipid metabolism. This includes inhibition of lipid accumulation in macrophages, mobilization of lipids from adipose tissue and beneficial effects on lipoprotein metabolism, involving SIRT1 and FoxO. It is particularly, challenging that extracellular and intracellular NAMPT may have different or even opposite effects. Further studies are needed to clarify if NAMPT could be a missing link in atherogenesis, connecting inflammation and dysregulated lipid metabolism – the two hallmarks of atherosclerosis.

Lipid oxidation by hypochlorous acid: chlorinated lipids in atherosclerosis and myocardial ischemia.

Leukocytes, containing myeloperoxidase (MPO), produce the reactive chlorinating species, HOCl, and they have important roles in the pathophysiology of cardiovascular disease. Leukocyte-derived HOCl can target primary amines, alkenes and vinyl ethers of lipids, resulting in chlorinated products. Plasmalogens are vinyl ether-containing phospholipids that are abundant in tissues of the cardiovascular system. The HOCl oxidation products derived from plasmalogens are α-chlorofatty aldehyde and unsaturated molecular species of lysophosphatidylcholine. α-chlorofatty aldehyde is the precursor of both α-chlorofatty alcohol and α-chlorofatty acid. Both α-chlorofatty aldehyde and α-chlorofatty acid accumulate in activated neutrophils and have disparate chemotactic properties. In addition, α-chlorofatty aldehyde increases in activated monocytes, human atherosclerotic lesions and rat infarcted myocardium. This article addresses the pathways for the synthesis of these lipids and their biological targets.

Detection of lipid in atherosclerotic vessels using ultrasound-guided spectroscopic intravascular photoacoustic imaging

Lipid is a common constituent in atherosclerotic plaques. The location and area of the lipid region is closely related to the progression of the disease. Intravascular photoacoustic (IVPA) imaging, a minimally invasive imaging modality, can spatially resolve the optical absorption property of arterial tissue. Based on the distinct optical absorption spectrum of fat in the near infrared wavelength range, spectroscopic IVPA imaging may distinguish lipid from other water-based tissue types in the atherosclerotic artery. In this study, a bench-top spectroscopic IVPA imaging system was used to ex-vivo image both atherosclerotic and normal rabbit aortas. By combing the spectroscopic IVPA image with the intravascular ultrasound (IVUS) image, lipid regions in the aorta were identified. The results demonstrated that IVUS-guided spectroscopic IVPA imaging is a promising tool to differentiate lipid in atherosclerosis.