Atherosclerosis Cardiovascular Disease Research Articles

Effect of carbon disulfide exposure on fatty acid metabolism in ApoE knockout and C57BL/6J mice

To study the influences of carbon disulfide (CS2) exposure on fatty acid metabolism in apolipoprotein E (ApoE) knockout mice and C57BL/6J mice. Twenty-four male ApoE knockout mice were randomly and equally divided into four groups: a CS2-exposed normal diet group, a CS2-unexposed normal diet group, a CS2-exposed high-fat diet group, and a CS2-unexposed high-fat diet group. Twenty-four C57BL/6J male mice were divided into four groups in the same way. The CS2-exposed groups were exposed to CS2 (1 g/m(3)) by static inhalation for 5 hours a day, 5 days a week. After two weeks, the whole blood of mice was collected. Methyl ester derivatization of fatty acids was performed using an acid-catalyzed method. Fatty acid contents before and after exposure were compared by gas chromatography-mass spectroscopy. There were significant differences in fatty acid contents of mice between the four groups. For the C57BL/6J mice, the arachidic acid contents in the CS2-exposed high-fat diet group were significantly lower than those in the CS2-unexposed high-fat diet group (P = 0.045 0). For the ApoE knockout mice, the arachidonic acid contents in the CS2-exposed normal diet group were significantly lower than those in the CS2-unexposed control diet group (P = 0.045 2). For the ApoE knockout mice, the γ-linolenic acid contents in the CS2-exposed high-fat diet group were significantly higher than those in the unexposed high-fat diet group (P = 0.044 7). Exposure to CS2 can induce fatty acid metabolism disorder in mice, indicating that CS2 may increase the risk of atherosclerosis and other cardiovascular diseases.

A Prospective View of Therapeutic Strategy of Atherosclerosis in Cardiovascular Diseases

Submit Manuscript | http://medcraveonline.com and acute outbreak of stroke at the first time in China with imagine technology (CT and TCD) as early as in 1995 [1]. Then the team accessed and compared the four stroke evaluation scales that generally used in Europe; USA; Japan and China with acute stroke inpatients; which was the first time to bring the bridge of clinical research about stroke between China and the rest of world [2]. Knowing the significant of rehabilitation in outcome of stroke; Beijing Tiantan Hospital built stroke units setting for inpatients to satisfy the world standard of clinical research of stroke; and performed the therapeutic effects and prospective study of intervention and antiplatelet agents (Clopidogrel combining with Aspilin) application to atherosclerosis and stroke patients [3]; which provided the fundamental data for the guideline of primary and secondary prevention of cerebrovascular diseases in China. According to their achievement; an innovative system; Chinese Ischemic Stroke Subclassification (CISS) was created and spreadingly employed within hundreds hospitals offering standard and accurate classification for clinical information of stroke in China [4]. ACURE Biotechnology; INC.; backed with extensive basic and translational research in neuroscience; lipids metabolism; cell microenvironment; angiogenesis and infectious diseases; holds 5 patents in therapeutic and preventive strategies for vascular diseases. A novel gene with same N-terminal motif to G-couple proteins was originally discovered by this company’s founder as early as in 2001; had been demonstrated that is play important role in immune and brain associating with lipid rafts [5]. The founder later discovered that the intracellular accumulation of ceramide; the original backbone for most lipids; causes mitochondria dysfunction and leads to severe defect of development of cardiovascular in a Ceramide Transfer Protein (CERT) mutant mouse model [6]. Recently the company established an animal model studying the association between secretion of cytokines (IL17; VEGF) in infectious diseases and vascularization [7]. Thereby a hypothesize that mitochondria dysfunction of smooth muscle cells in vessels wall caused by hypertension; diabetes; high fat or glucose diets; viruses and bacteria infection; and diseases lowering blood oxygen; aging and degeneration diseases; produces abnormal lipids metabolites; which cause the local acute; then process to chronic inflammation; cell death and calcification--the pathological changes of atherosclerosis. Here address to this hypothesis; we summarize a comprehensive therapeutic strategy in atherosclerosis for our collaboration: Evaluating; monitoring and controlling the risk factors of stroke in a community system; Establishment of epigenetic gene markers to predict high-risk population of stroke for preventive medicine; Developing and discovering innovative immunotherapy and drugs to remove or stabilize atherosclerosis lesions; discovering new drugs to improve the formation of collateral circulation in brain after stroke; Combination of acute care; rehabilitation and traditional Chinese medicine to improve the outcome of stroke patients.

Abstract 342: Naturally Occurring Modified Forms of LDL

Electronegative LDL, small,dense LDL, and desialylated LDL circulating in the blood of patients were obtained by different methods. Naturally, the question arises what are the similarities and differences between these forms of LDL modification. We believe that multiple modified LDL particle (small, dense, electronegative, desialylated, etc.) occurs in blood. Ex vivo experiments have revealed mechanisms of multiple modification of LDL in the blood. Fraction of native LDL was isolated from blood plasma of healthy subjects. Blood serum of patients with assessed atherosclerosis was also obtained. LDL and serum were mixed and incubated for various periods at 37°C. After 1 hour incubation of native LDL with atherosclerotic serum desialylated LDL appears. After 3 hours, LDL becomes able to cause accumulation of cholesterol in cultured cells. After 6 hours, LDL demonstrates reduction of neutral lipids and phospholipids as well as reduction in its size. After 36 hours, an increase in the electronegativity of the lipoprotein particle is detected. After 48-72 hours, loss of α-tocopherol, increase of susceptibility to oxidation, and accumulation of lipid peroxidation products in LDL are observed. Thus, multiple modification of LDL is a cascade of sequential changes in lipoprotein particle, namely: desialylation, loss of lipids, size reduction, increase of electronegative charge, lipid peroxidation in LDL. Desialylation of LDL particle is one of the first or primary events of atherogenic modification. We have established that the reason of LDL desialylation is trans-sialidase. We found trans-sialidase activity in the blood of patients with atherosclerosis and other cardiovascular diseases. We have shown that human neuraminidases 2 and 4 possess trans-sialidase activity. On the other hand, selective inhibitors of viral sialidases suppress trans-sialidase activity in the blood of atherosclerotic patients. Thus, trans-sialidase causing atherogenic desialylation of LDL may be of both endogenous and exogenous origin. Supported by Russian Ministry of Education and Science (Project RFMEFI61614X0010).

The Promise of Proprotein Convertase Subtilisin/Kexin 9 Inhibitors for the Treatment of Familial Hypercholesterolemia

Familial hypercholesterolemia comprises a constellation of genetic disorders resulting in very high cholesterol levels since childhood. If untreated, it is associated with accelerated atherosclerosis and premature cardiovascular disease. It has been shown that if aggressive cholesterol lowering is achieved in familial hypercholesterolemia, the incidence of cardiovascular disease can be lowered. However, currently approved pharmacological therapies are not able to lower cholesterol to optimal levels in a large number of these patients. Proprotein convertase subtilisin/kexin 9 inhibitors are a new class of cholesterol-lowering medications that can significantly reduce cholesterol levels in these patients especially those with at least some functioning low-density lipoprotein receptors. In this article, we will briefly review familial hypercholesterolemia and the role of proprotein convertase subtilisin/kexin 9 inhibitors in this condition.

Intraocular pressure and coronary artery calcification in asymptomatic men and women

ObjectiveWe evaluated the relationship between intraocular pressure (IOP) and the risk of coronary artery calcification as a predictable marker of cardiovascular disease (CVD) in a large study of asymptomatic men...

The Effect of Periodontal Therapy on Atherosclerosis in Cardiovascular Disease: Clinical, Biochemical, Microbiological and Experimental Study

The Effect of Periodontal Therapy on Atherosclerosis in Cardiovascular Disease: Clinical, Biochemical, Microbiological and Experimental Study Objective: The goal of the present study is to assess the effect of periodontal therapy on atherosclerotic changes of cardiovascular patients, in terms of lipid profile and microbiological investigation. It is also to assess the impact of oral inoculation and atheroma with the periodontal pathogen Porphyromonas gingivalis on atherogenesis in hypercholesterolemic mice. Methods: The study comprises of two parts. Part I: a total of thirty subjects with age range 40-65 were selected for this study and these subjects were divided into three groups. Group (I) periodontitis, group (II) periodontitis with cardiovascular disease and group (III) cardiovascular disease. Part II: fifteen mice were divided into two groups. Group (Ι) (study group) with 10 mice and control group (II) included 5 mice. Group (Ι) had undergone high lipid diet and topical application of P. gingivalis bacteria three times a week for one month while the control group received low diet only. Results: The clinical results of both group (I) and group (II) showed the clinical parameters: popliteal-brachial index (PBI), probing pocket depth (PPD) and clinical attachment level (CAL) were statistically significant difference in clinical parameters after four weeks of treatment. Microbiologically, results of microbial evaluation showed that, P. intermedia and P. gingivalis count decreased significantly after treatment in both group (I) and group (II). Pathologically, results of lipid profile evaluation showed that, TG, LDL, HDL and cholesterol levels decreased significantly after treatment in both group (I) and group (II). Experimental results showed that the total cholesterol level was significantly higher in study group after one month of high lipid diet and topical application of P. gingivalis. In addition, after the heart and aorta were obtained, they were observed for atherosclerotic lesion. The obtained tissue was grinded and cultured on BHI broth aerobically then subculture was done on brain heart infusion agar (Oxoid) supplemented with 5.0 μg/ ml hemin for detection of P. gingivalis. The P. gingivalis was isolated from four atherosclerotic lesions out of ten in the study group while was not detectable in the control group. Conclusion: Non-surgical periodontal treatment in chronic periodontitis patients could cause significant changes in lipid levels and help in preventing any systemic complications due to the elevated lipid levels. The presence of periodontal bacteria in atheromatous plaques was confirmed by this investigation and, there is correlation between periodontitis bacteria and microorganisms involved in the atherosclerotic lesions.

Assessment of serum levels of MMP-8 and hs CRP in chronic periodontitis patients in relation to atherosclerotic cardiovascular disease

Periodontitis and Atherosclerosis Cardiovascular disease are chronic inflammatory diseases which are highly prevalent. During the last two decades, there has been an increasing interest in the impact of oral health on atherosclerosis and subsequent cardiovascular disease. The aims of the study were to evaluate the periodontal health status in study groups (Atherosclerotic cardiovascular disease patients with chronic periodontitis and patients having chronic periodontitis),to estimate the serum levels of Matrixmetalloproteinase-8(MMP-8) and high sensitive C- reactive protein(hs CRP) in study and control groups and compare between them. Also,test the correlation between the serum levels of MMP-8 and hs CRP with clinical periodontal parameters at each study group Subjects, materials and methods: Eighty subjects, males and females were included in this study with age range (35- 50) years old, they were divided into study groups (ATH+CP group: Atherosclerotic cardiovascular disease& chronic periodontitis group (30 patients ), CP group: chronic periodontitis group (30 patients )) andcontrol group: (20 systemically healthy subjects, have healthy periodontium). Periodontal health status was determined by measuring the following clinical periodontal parameters (Plaque index (PL.I), Gingival index (GI), Bleeding on probing (BOP), Probing pocket depth (PPD) and Clinical attachment level (CAL)).Serum levelsof (MMP-8and hs CRP) were determined by mean of ELISA. Results: The results showed that the mean values of clinical periodontalparameters (PL.I, GI, PPD and CAL), were higher in the ATH+CP group than in the CP group with significant differences except in PL.I there was no significant difference. A higher percentage of score 1of BOP sites demonstrated by CP groupthan in ATH+CP group with highly significant difference.The levels of serum (MMP-8 and hs CRP) were higher in ATH+CP groupwhen compared with CP group and control group, with highly significant differences between all pairs of study and control groups.Regarding the Correlation between serum levels of (MMP-8 and hs CRP) and clinical periodontal parameters, were positive correlation in both study groups. Conclusion: The present results my provide evidence that Chronic Periodontitis may contribute to the inflammation- associated to atherosclerotic process

Abstract 20310: Cardiovascular Risk Markers in a Large Cohort of Children With Genetically Verified FH Show No Inheritance-Related but LDL Receptor Mutation-Type and Family History of CVD-related Variance

Introduction: Familial hypercholesterolemia (FH) is an autosomal dominant disease caused primarily by mutations in the low density lipoprotein (LDL) receptor gene. FH patients have increased total- and LDL cholesterol leading to accelerated atherosclerosis and premature cardiovascular disease (CVD). In an FH pregnancy the absolute rise in lipid levels are often much higher than in healthy pregnancies, and this maternal hypercholesterolemia may thus contribute to an unfavorable in utero environment potentially increasing susceptibility of adult CVD. Few studies have investigated whether maternal FH is associated with an unfavorable phenotype in offspring compared with paternal FH inheritance. Hypothesis: The aim of the present study was to investigate the impact of maternal vs. paternal FH on pre-treated plasma lipids. In addition, the effect of LDL receptor mutation types and Family history of early CVD in FH children was evaluated Methods: We included 1063 children with FH (0-19 years) in the study. Five-hundred had inherited FH maternally and 563 paternally. Furthermore, 624 children with FH had an LDL receptor negative mutation and 332 of the FH children had an FH grandparent suffering from early CVD whereas the remaining children had an FH grandparent with late or no CVD. Differences were tested for using a random intercept mixed model taking account for between-family variation. Results: Children with maternal FH did not have different levels of total-, LDL- or HDL-cholesterol, triglycerides, apoA1, apoB, lipoprotein (a) compared with children With paternal FH. Moreover, children with LDL receptor negative mutations had higher levels of total- and LDL cholesterol in addition to apoB, and concomitantly lower levels of HDL-cholesterol and apoA-1 than children with other LDL receptor mutations. Finally, children with an FH grandparent with early CVD had significant higher LDL-cholesterol levels than children without. Conclusions: Maternal FH does not lead to a more unfavorable phenotype in untreated FH children. However, both FH children with LDL receptor negative mutation and FH children with early CVD in family had a more unfavorably phenotype. Hence statin treatment should potentially be initialized earlier in this group.

GW25-e1527 Cardioprotective Effects of Angiotensin-Converting Enzyme 2 in Apolipoprotein E-Deficient Mice in Response to Angiotensin II

Inhibition of the renin-angiotensin system (RAS) has lead to important pharmacological tools to treat atherosclerosis and other cardiovascular diseases. Angiotensin-converting enzyme 2 (ACE2) has emerged as a central negative regulator of RAS by degrading angiotensin (Ang) II to generate Ang-(1-7).

Evaluation of low-density lipoprotein cholesterol as an indicator to reduce atherosclerosis cardiovascular risk

Objectives: Low-density lipoprotein cholesterol (LDL-C) is estimated as an indicator of risk factor for atherosclerosis cardiovascular disease (CVD) and also as an indicator of the treatment target for the prevention of CVD. There are some problems in the measuring method of LDL-C. The concept of non high-density lipoprotein cholesterol (HDL-C) is also presented as an indicator by atherosclerotic disease prevention guidelines of Japan in 2012. We investigated LDL-C levels in the comparison of a direct method and Friedewald equation, and the relation between non-HDL-C and LDL-C including clinical backgrounds.

Abstract 638: Urotensin II Promotes Calcification in Vascular Smooth Muscle Cells

Introduction: Atherosclerosis is a leading cause of death in Western societies. Vasoactive peptide urotensin II (UII) is upregulated in atherosclerosis and several other cardiovascular diseases however further research is required to develop a complete understanding of UII’s role in the pathogenesis of atherosclerosis. Hypothesis: We hypothesized that UII stimulates calcification in vascular smooth muscle cells and that UII, urotensin II related peptide (URP) and UT receptor expression are upregulated in calcified aortic valves. Methods and Results: Human aortic smooth muscle cells (HASMC) were cultured in phosphate media (2.6mmol/L) for 13 days in the presence of varying concentrations of UII (0, 10, 50, 100nm) and the amount of calcium was measured with a calcium assay kit. Protein was extracted and measured with a protein assay kit. HASMC calcification was assessed as the ratio of calcium (μg)/protein (mg). HASMC calcification increased with increasing UII concentration and was significantly elevated in 100nm of UII (N=6, P<0.05) 13 days after incubation. We also examined UII, URP and UT protein expression in 90 carotid endarterectomies and 87 mitral, non-calcified and calcified aortic valves by immunohistochemistry. Multivariant Spearman correlation analyses in carotids revealed significant positive correlations between UII, URP and UT overall staining with calcification, remodeling and inflammation (P<0.05). In valves there was significant positive correlations between UII, URP and UT overall staining with calcification, fibrosis, remodeling, inflammation, lipid score and microvessels (P<0.05). Conclusion: The stimulatory effect of UII on vascular smooth muscle cell calcification as well as the upregulated expression of UII, URP and UT in calcified aortic valves suggests that the UT receptor system plays a key role in the pathogenesis of atherosclerosis and valve calcification.

Soluble C5b-9, a marker for terminal complement activation, is not associated with markers of atherosclerosis or prevalent cardiovascular disease: The CODAM study

Soluble C5b-9, a marker for terminal complement activation, is not associated with markers of atherosclerosis or prevalent cardiovascular disease: The CODAM study

AB0722 Prevalence of metabolic syndrome in patients with systemic lupus erythematosus

BackgroundSystemic lupus erythematosus (SLE) is a multisystem inflammatory disease characterized by varied clinical manifestations. It mainly affects women of childbearing age and varies in intensity from a mild disease with...

A 64-year-old patient with heart failure and 'chronic liver disease': looking at the liver, the myocardium or the pericardium?

Role of adiponectin in early atherosclerosis and incident cardiovascular disease in high-risk European subjects

Abstract P391: Marine N-3 Fatty Acids Reduce Atherosclerosis Cardiovascular Disease: A Systemic Review and Meta-analysis of Clinical Trials

Introduction: Although marine n-3 fatty acids are believed to be cardioprotective through their anti-arrhythmic, anti-thrombotic, anti-atherogenic and other effects, results from recent meta-analyses of marine n-3 fatty acids on cardiovascular disease (CVD) are controversial. We performed a meta-analysis of marine n-3 fatty acids on CVD outcomes in randomized clinical trials (RCTs) to test the hypothesis that marine n-3 fatty acids are anti-atherogenic. We also tested the hypothesis that such benefit is dose-dependent. Methods: A systematic review of English language articles using PubMed, EMBASE and Cochrane Library through Aug 2012 was performed selecting RCTs evaluating the effect of marine n-3 fatty acids intake for 2 years or more on cardiovascular diseases, coronary disease, arteriosclerosis, cardiac imaging techniques, and carotid artery ultrasound. Descriptive and quantitative information was extracted. Odds ratios were calculated for cardiac event outcome. Correlation coefficients were obtained from studies of which outcome is intima-media thickness (IMT) and coronary lumen diameter (CD). We converted the estimates into a single effect size; the log odds ratio and its corresponding standard error. Results: Of 14,236 citations retrieved, 13 studies were selected, including studies reporting IMT (n=3) and CD (n=2) and major CVD events (n=8). Overall, marine n-3 fatty acids significantly reduced atherosclerotic CVD (RR 0.94: 95%CI 0.90 to 0.99, p<0.05). There was no evidence of heterogeneity (p=0.65) or publication bias (p=0.37, Begg’s test). A sub-analysis among 8 studies of major CVD events showed the similar results (RR 0.94: 95% CI 0.89 to 0.99, p<0.05). Another sub-analysis among 4 studies excluding sudden cardiac death as an outcome showed RR of 0.91 (95% CI 0.82 to 1.02, p=0.097). A meta-regression analysis shows that dose of marine n-3 fatty acids was inversely associated with CVD outcome, although the association was not statistically significant (p=0.06). Conclusions: The result of our meta-analysis supports a modest anti-atherogenic effect of marine n-3 fatty acids. This benefit may be proportional to the amount of marine n-3 fatty acids consumed.

Cardiovascular Inflammation 2012: Reactive Oxygen Species, SUMOylation, and Biomarkers in Cardiovascular Inflammation

Cardiovascular diseases are growing burden in westernized countries. Cardiovascular diseases, including atherosclerosis, associate with chronic inflammation. The goal of this special issue is to highlight the inflammatory nature of cardiovascular diseases and their association with the production of cytokines, reactive oxygen species (ROS), and SUMOylation in atherosclerotic plaques. In addition, biomarkers that reflect the biological processes of progression and destabilization of atherosclerotic plaques would provide noninvasive means to identify high-risk patients for cardiovascular events. Armed with this understanding, it is hoped that novel therapeutic strategies will aid in the prevention and management of chronic cardiovascular inflammation and benefit the patients afflicted with cardiovascular disease. Increasing pieces of evidence support the important role of ROS and cytokine production in the process of atherosclerosis via regulating various signaling pathways leading to vascular inflammation. In the present review, N. T. Le et al. focused on ROS-mediated SUMOylation, which is one of the posttranslational modifications, and discussed its possible implications on vascular inflammation. It becomes apparent that ROS production can regulate the process of SUMOylation in both vasculature and heart and mediate a number of biological processes, such as apoptosis and inflammation. The crucial role especially of ERK5, p53, and MK2 SUMOylation in the process of endothelial inflammation has been discussed. Furthermore, a recent study from their group has found a strong correlation between C247T SNP of the NADPH oxidase p22phox subunit and cardiovascular events in postinfarction patients with concurrently high levels of HDL cholesterol and CRP. These data suggest that ROS not only affects the intracellular signaling but also can produce dysfunctional HDL. Since ROS can increase nitration and chlorination of specific tyrosine residues on apolipoproteinA-I, which is a major apolipoprotein component of HDL particles and major mediator of HDL functionalities, it is intriguing to assume that C247T SNP of the NADPH oxidase p22phox subunit relates to this HDL modification, leading to dysfunctional HDL. R. N. England and M. V. Autieri discussed the role of novel and undercharacterized cytokine IL-19 on vascular inflammation. IL-19 shows pleotropic effects on vascular wall. It can inhibit proliferative and proinflammatory gene expression in vascular smooth muscle cells (VSMCs) via NF-kB independent signaling, which is very different from the effects of IL-10. The possible involvement of the expression of suppressor of cytokine signaling 5 (SOCS5), human R antigen (HuR), and hem oxygenase-1 (HO-1) in this inhibitory effect has been discussed. In contrast to VSMCs, IL-19 showed proliferative, promigratory, and proangiogenic effects in vascular endothelial cells (ECs), although its role in EC inflammation remains unclear. Since IL-19 can inhibit ROS production and atherosclerosis formation in a mouse model, investigation the exact mechanisms of and interplay between IL-19 and ROS in both VSMCs and ECs will be valuable for orchestrating anti-inflammatory therapies for cardiovascular events. Biomarkers can reflect the biological processes of disease progression. For instance, CRP levels have been shown to be predictive of cardiovascular risk. However, CRP is a nonspecific inflammatory marker that is affected by any inflammatory conditions. Therefore, it is important to develop biomarkers that specifically report the biological processes in atherosclerosis and other cardiovascular diseases, associated with chronic inflammation. N. Kafkas et al. showed that serum neutrophil gelatinase-associated lipocalin (NGAL) levels were increased in patients with coronary artery disease. They propose that NGAL could be used to discriminate patients with acute coronary syndrome from those who are with stable angina or without coronary artery diseases. V. Panichi et al. review newer biomarkers, including CD40 ligand and pentraxin-3 that reflect chronic inflammation in cardiovascular and renal diseases. D. Vasic and D. Walcher summarize the current knowledge about C-peptide as a biomarker and bioactive molecule. The deposition of C-peptide may promote inflammation. The docking proteins of the Grb2-associated binder family (Gab1, Gab2, and Gab3) serve as important signaling compartments. They may amplify and integrate signal transduction pathways in response to various stimuli such as cytokines. Interestingly, recent evidence has linked abnormal Gab signaling with human diseases including cancer and cardiovascular disease, for which inflammation plays a key role. Y. Nakaoka and I. Komuro. extensively described molecular structure, recruitment, and phosphorylation of Gab proteins and discussed their role in cardiovascular and cancer inflammation. An emerging concept suggests that chronic inflammation participates in the pathogenesis of atherosclerosis and other cardiovascular diseases. Thus, controlling proinflammatory pathways such as ROS-mediated SUMOylation may attenuate such diseases. The goal of this thematic series is to highlight emerging proinflammatory mechanisms involved in cardiovascular inflammation. We believe that this issue will offer updated concepts and help readers develop ideas leading to future investigations and new drug development. Jun-Ichi Abe Ichiro Manabe Masanori Aikawa Elena Aikawa

Hyperhomocysteinemia and Increased Oxidative Stress Levels Are Associated with Impaired Membrane Fluidity of Red Blood Cells in Hypertensive and Normotensive Men: An Electron Spin Resonance Investigation

Hyperhomocysteinemia and oxidative stress may be strongly linked to hypertension, atherosclerosis and other cardiovascular diseases. The present study was performed to investigate possible relationships among plasma total homocysteine, plasma 8-iso-prostaglandin F2α (8-isoPG F2α: an index of oxidative stress), and membrane fluidity (a reciprocal value of membrane microviscosity) in hypertension. We measured the membrane fluidity of red blood cells (RBCs) in hypertensive and normotensive men using an electron spin resonance (ESR) and spin-labeling method. Membrane fluidity of RBCs was significantly decreased in hypertensive men compared with normotensive men. Plasma total homocysteine levels were significantly higher in hypertensive men than in normotensive men, and correlated with plasma 8-isoPG F2α. In contrast, plasma nitric oxide (NO)-metabolites (an index of endothelial function) were lower in hypertensive men than in normotensive men. The reduced membrane fluidity of RBCs was associated with increased total homocysteine and plasma 8-isoPG F2α levels and decreased plasma NO-metabolite levels. Multivariate regression analysis showed that, after adjusting for general risk factors, plasma total homocysteine and 8-isoPG F2α were significant determinants of membrane fluidity of RBCs, respectively. These results suggest that hyperhomocysteinemia and oxidative stress with endothelial dysfunction might have a close correlation with impaired rheologic behavior of RBCs and circulatory disorders in hypertensive men.

Macrophage Migration Inhibitory Factor Is Enhanced in Acute Coronary Syndromes and Is Associated with the Inflammatory Response

BackgroundChronic inflammation promotes atherosclerosis in cardiovascular disease and is a major prognostic factor for patients undergoing percutaneous coronary intervention (PCI). Macrophage migration inhibitory factor (MIF) is involved in the progress of atherosclerosis and plaque destabilization and plays a pivotal role in the development of acute coronary syndromes (ACS). Little is known to date about the clinical impact of MIF in patients with symptomatic coronary artery disease (CAD).Methods and ResultsIn a pilot study, 286 patients with symptomatic CAD (n = 119 ACS, n = 167 stable CAD) undergoing PCI were consecutively evaluated. 25 healthy volunteers served as control. Expression of MIF was consecutively measured in patients at the time of PCI. Baseline levels of interleukin 6 (IL-6), “regulated upon activation, normal T-cell expressed, and secreted” (RANTES) and monocyte chemoattractant protein-1 (MCP-1) were measured by Bio-Plex Cytokine assay. C-reactive protein (CRP) was determined by Immunoassay. Patients with ACS showed higher plasma levels of MIF compared to patients with stable CAD and control subjects (median 2.85 ng/mL, interquartile range (IQR) 3.52 versus median 1.22 ng/mL, IQR 2.99, versus median 0.1, IQR 0.09, p<0.001). Increased MIF levels were associated with CRP and IL-6 levels and correlated with troponin I (TnI) release (spearman rank coefficient: 0.31, p<0.001). Patients with ACS due to plaque rupture showed significantly higher plasma levels of MIF than patients with flow limiting stenotic lesions (p = 0.002).ConclusionTo our knowledge this is the first study, demonstrating enhanced expression of MIF in ACS. It is associated with established inflammatory markers, correlates with the extent of cardiac necrosis marker release after PCI and is significantly increased in ACS patients with “culprit” lesions. Further attempts should be undertaken to characterize the role of MIF for risk assessment in the setting of ACS.

Abstract P088: Lean Locomotor Muscle Mass Associated With Elevated Depressive Symptoms: The Multi-Ethnic Study of Atherosclerosis

Lean Locomotor Muscle Mass Associated With Elevated Depressive Symptoms: The Multi-Ethnic Study of Atherosclerosis Rosemay A Remigio-Baker, MPH, PhDc, Matthew A Allison, MD, MPH, PhD, MPH, Pamela J Schreiner, PhD, MS, MS, Mercedes R Carnethon, PhD, Jennifer A Nettleton, PhD, Mahasin J Mujahid, PhD, Moyses Szklo, MD, DrPH, Rosa M Crum, MD, MPH, Manuel Franco, MD, PhD, Nicole Jensky, PhD, Sherita Hill Golden, MD, MHS BACKGROUND: Physical activity reduces depressive symptoms but it is unclear whether one physiologic response to activity, higher lean muscle mass, is associated with depression. METHODS: Using data from 976 men and women (45-84 years) from the Multi-Ethnic Study of Atherosclerosis (MESA) Body Composition, Inflammation and Cardiovascular Disease and the MESA Neighborhood Ancillary Studies, we examined the cross-sectional association between elevated depressive symptoms (EDS, defined as a Center for Epidemiologic Studies for Depression Scale (CES-D) score &gt; 16) and CT-measured lean muscle mass in the abdomen using multilevel mixed-effects linear regression models. Muscles were categorized by functionality (locomotion vs. stabilization/posture) and combined (see Table). Covariates included demographics, antidepressant use, inflammatory markers, health behaviors, social support, comorbidities, body mass index (BMI) and neighborhood factors: physical and social environment (see Table). Gender, physical environment and social environment were also assessed as potential modifiers. RESULTS: Lean mass of muscle for locomotion was 4.25% lower among participants with EDS compared to those without after adjustment for demographics and antidepressant use (95% CI=-8.20, -0.30; see Table). This association remained significant after additional adjustment for inflammatory markers, health behaviors, social support, comorbidities, neighborhood factors and BMI (see Table). Results were significant in the fully-adjusted model (see Table). No association was observed between EDS and muscle for stabilization/posture. There were no interactions by gender or neighborhood factors. CONCLUSION: Elevated depressive symptoms is associated with less lean muscle for locomotion independent of obesity and physical activity; however, further investigation is necessary in larger samples to confirm and determine the clinical relevance of this association. TABLE Percent Difference a in Lean Muscle Mass b , in cm 2 , (95% Confidence Interval) Between Individuals With Versus Without Elevated Depressive Symptoms By Muscle Category c MODEL All Muscle Locomotion d Stabilization/ Posture e MODEL 1: Univariate −5.75 (-11.0, -0.49)+ −9.25 (-15.3, -3.25)+ −5.04 (-10.4, 0.28) MODEL 2: Demographics f −1.96 (-4.94, 1.01) −4.35 (-8.30, -0.45)+ −1.48 (-4.58, 1.62) MODEL 3: Model 1 + Antidepressant Use −1.88 (-4.88, 1.11) −4.25 (-8.20, -0.30)+ −1.40 (-4.52, 1.72) MODEL 4: Model 3 + Inflammatory Markers g −1.84 (-4.83, 1.15) −4.20 (-8.15, -0.25)+ −1.38 (-4.49, 1.75) MODEL 5: Model 3+ Health Behaviors h −2.28 (-5.26, 0.68) −4.35 (-8.25, -0.45)+ −1.85 (-4.95, 1.25) MODEL 6: Model 3+ Social Support −1.75 (-4.83, 1.33) −4.35 (-8.45, -0.30)+ −1.22 (-4.43, 1.98) MODEL 7: Model 3 + Comorbidity i −1.89 (-4.88, 1.10) −4.05 (-8.00, -0.10)+ −1.45 (-4.56, 1.66) MODEL 8: Model 3 + Neighborhood Factors j −1.49 (-4.47, 1.48) −4.20 (-8.15, -0.25)+ −0.99 (-4.09, 2.11) MODEL 9: Model 3 + Body Mass Index −2.46 (-5.36, 0.45) −4.60 (-8.55, -0.70)+ −1.98 (-5.03, 1.05) MODEL 10: Fully-Adjusted Model −2.11 (-5.07, 0.85) −4.55 (-8.55, -0.60)+ −1.66 (-4.76, 1.44) a Percent difference is calculated by diving the estimate by the mean of the muscle category (x100). b Mean (range): for all muscle mass [117.3 cm 2 (42.9-228.7 cm 2 )]; for locomotion muscle mass [20.0 cm 2 (4.7-40.7 cm 2 )]; for stabilization/posture muscle mass [97.3 cm 2 (36.9 - 198.3 cm 2 )] c There were no significant interaction by gender, physical environment or social environment d Muscle for locomotion: psoas e Muscle for stabilization and posture: rectus abdominus, obliques, paraspinal f Demographics: age, race, gender, marital status, study site, highest level of education attained, income level g Inflammatory Markers: Interleukin-6, C-reactive protein h Health Behaviors: Pack-years of smoking, alcohol intake/week, total intentional exercise, daily caloric intake, dietary patterns (1. High-fat and processed food; 2. Vegetables and fish; 3. Beans, tomatoes and refined grains; 4. Whole grain and fruits) i Comorbidity: Having at least one of the following: Cancer, Type II Diabetes and Hypertension j Neighborhood Factors: Median Income, % with High School education, Physical Environment (walking environment, availability of healthy foods), Social Environment (aesthetic quality, safety and social cohesion) + Significant p-value &lt; 0.05

Abstract P046: Circulating Levels of Persistent Organic Pollutants are Related to the Change in Lipids During 5 Years Follow Up

Background: When reporting circulating levels of persistent organic pollutants (POPs), usually lipid-normalized values are given. However, animal experiments and some human data support the view that exposure to POPs might change lipid values. The aim of the present study is to investigate if POP levels could predict future change in lipids levels. Methods: In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, lipids were measured at age 70 and at age 75 in 598 subjects without lipid-lowering medication. Twenty-one different POPs, including 16 PCBs, three pesticides (HCB, DDE and TNK), one dioxin (OCDD) and one brominated compound (BDE47) were analyzed by high-resolution chromatography coupled to high-resolution mass spectrometry (HRGC/ HRMS) at age 70. Results: Strong relationships were seen between the baseline levels of PCBs 194, 206 and 209 and the degree of increase in total serum cholesterol and LDL-cholesterol during the 5 year follow-up. These relationships were generally stronger when lipid-normalized levels were used compared to wet-weight based levels. On the contrary, both HCB and TNK levels were inversely related to the change in LDL-cholesterol, with strongest associations found using wet-weight based levels. PCBs 194, 206 and 209 were inversely related to the change in HDL-cholesterol. None of the POPs were related to the change in serum triglycerides. Conclusion: POPs are related to the future change in lipids. This might explain why POP exposure previously has been linked to atherosclerosis and future cardiovascular disease. It might also question the use of lipid-normalization when studying relationships between POPs and metabolic diseases.