Sound of Stockholm

DEFF Research Database (Denmark)

Groth, Sanne Krogh

2013-01-01

Med sine kun 4 år bag sig er Sound of Stockholm relativt ny i det internationale festival-landskab. Festivalen er efter sigende udsprunget af en større eller mindre frustration over, at den svenske eksperimentelle musikscenes forskellige foreninger og organisationer gik hinanden bedene, og...

Gene/Environment Interaction in Atherosclerosis: An Example of Clinical Medicine as Seen from the Evolutionary Perspective

Directory of Open Access Journals (Sweden)

Gerhard Mertens

2010-01-01

The chronic multifactorial disease of atherosclerosis clearly illustrates the Darwinian paradigm. Recent research, combining the effects of genes and environment, has provided surprising clues to the pathogenesis of this major public health problem. This example makes a strong case for recognizing evolution biology as a basic science for medicine.

Impressions from the ATLAS Overview Week in Stockholm

CERN Document Server

De Jong, P.; Gowdy, S.

2006-01-01

Paul de Jong: "What a very nice city Stockholm in the summer turned out to be! The architecture, the relaxed style of the city and its islands and bridges, the terraces with people out on the streets until late at night made this a special trip. We visited many cool and trendy places, unfortunately many of those places are probably now a lot less cool and trendy after visits of so many physicists in shorts and white socks in sandals. A big applause for the organizers for a fine meeting, and getting us into the Stockholm city hall and the superb Wasa museum. (left) The Golden room of Stockholm City Hall. (right) Muriel was not the only one in the room entertaining noble dreams during the reception in the Golden Room of the Stockholm City Hall... ATLAS is a monstrously complicated piece of apparatus. It will be very impressive when it is finished and works, but there are so many places where things can go wrong. If I must name a single highlight of the week: I found the technical coordination of t...

Identifying novel genes for atherosclerosis through mouse-human comparative genetics

NARCIS (Netherlands)

Wang, XS; Ishimori, N; Korstanje, R; Rollins, J; Paigen, B

Susceptibility to atherosclerosis is determined by both environmental and genetic factors. Its genetic determinants have been studied by use of quantitative- trait - locus ( QTL) analysis. So far, 21 atherosclerosis QTLs have been identified in the mouse: 7 in a high- fat - diet model only, 9 in a

Genomic Analysis of Circulating Cells: A Window into Atherosclerosis

Science.gov (United States)

Kang, Ju-Gyeong; Patino, Willmar D.; Matoba, Satoaki; Hwang, Paul M.

2006-01-01

Translational studies using genomic techniques in cardiovascular diseases are still in their infancy. Access to disease-associated cardiovascular tissues from patients has been a major impediment to progress in contrast to the diagnostic advances made by oncologists using gene expression on readily available tumor samples. Nonetheless, progress is being made for atherosclerosis by carefully designed experiments using diseased tissue or surrogate specimens. This review details the rationale and findings of a study using freshly isolated blood mononuclear cells from patients undergoing carotid endarterectomy due to atherosclerotic stenosis and from matched normal subjects. Using this cardiovascular tissue surrogate, the mRNA levels of the Finkel-Biskis-Jinkins osteosarcoma (FOS) gene in circulating monocytes were found to correlate with atherosclerosis severity in patients, and with HMG CoA reductase inhibitor (statin) therapy in normal subjects. The major finding of this investigation is discussed in relation to observations from other human atherosclerosis gene expression studies. These distinct studies converge to demonstrate the unequivocal importance of inflammation in atherosclerosis. Although the clinical utility of the specific findings remains open, the identification of similar genes by different investigations serves to validate their reports. They also provide us with insights into pathogenesis that may impact future translational applications. PMID:16781950

Human Lipoxygenase Pathway Gene Variation and Association with Markers of Subclinical Atherosclerosis in the Diabetes Heart Study

Directory of Open Access Journals (Sweden)

Kathryn P. Burdon

2010-01-01

Conclusions. Polymorphisms within ALOX12, ALOX5, and ALOX5AP are genetically associated with subclinical atherosclerosis and with biomarkers of disease in families with type 2 diabetes. These results suggest that variants in lipoxygenase pathway genes may have pleiotropic effects on multiple components that determine risk of cardiovascular disease.

Soome kindlus Stockholmis : Soome Suursaatkond = Finnish Stronghold in Stockholm : Finnish Embassy in Stockholm / Kristian Gullichsen

Index Scriptorium Estoniae

Gullichsen, Kristian

2004-01-01

Soome suursaatkonna (Gärdesgatan, Stockholm) projekteeris büroo Gullichsen Kairamo Arkkidehdit. Autorid Kristian Gullichsen, Jyri Haukkavaara, sisekujundaja Aulikki Jylhä. Projekt 1996, valmis 2002. I ja II korruse plaan, 4 sise- ja 4 välisvaadet

Polymorphisms of genes involved in polycyclic aromatic hydrocarbons’ biotransformation and atherosclerosis

Science.gov (United States)

Marinković, Natalija; Pašalić, Daria; Potočki, Slavica

2013-01-01

Polycyclic aromatic hydrocarbons (PAHs) are among the most prevalent environmental pollutants and result from the incomplete combustion of hydrocarbons (coal and gasoline, fossil fuel combustion, byproducts of industrial processing, natural emission, cigarette smoking, etc.). The first phase of xenobiotic biotransformation in the PAH metabolism includes activities of cytochrome P450 from the CYP1 family and microsomal epoxide hydrolase. The products of this biotransformation are reactive oxygen species that are transformed in the second phase through the formation of conjugates with glutathione, glucuronate or sulphates. PAH exposure may lead to PAH-DNA adduct formation or induce an inflammatory atherosclerotic plaque phenotype. Several genetic polymorphisms of genes encoded for enzymes involved in PAH biotransformation have been proven to lead to the development of diseases. Enzyme CYP P450 1A1, which is encoded by the CYP1A1 gene, is vital in the monooxygenation of lipofilic substrates, while GSTM1 and GSTT1 are the most abundant isophorms that conjugate and neutralize oxygen products. Some single nucleotide polymorphisms of the CYP1A1 gene as well as the deletion polymorphisms of GSTT1 and GSTM1 may alter the final specific cellular inflammatory respond. Occupational exposure or conditions from the living environment can contribute to the production of PAH metabolites with adverse effects on human health. The aim of this study was to obtain data on biotransformation and atherosclerosis, as well as data on the gene polymorphisms involved in biotransformation, in order to better study gene expression and further elucidate the interaction between genes and the environment. PMID:24266295

Incidence of lung cancer among subway drivers in Stockholm.

Science.gov (United States)

Gustavsson, Per; Bigert, Carolina; Pollán, Marina

2008-07-01

Very high levels of airborne particles have been detected in the subway system in Stockholm. Subway particles are more toxic to DNA in cultured human lung cells than particles from ambient air. This cohort comprised all men in Stockholm County who were gainfully employed in 1970. They were followed for cancer incidence until 1989. Lung cancer cases were identified from the national cancer register. Subway drivers were identified from the census in 1970. The reference cohort comprised all transport and communication workers in Stockholm. There were nine cases of lung cancer among the subway drivers, giving a SIR of 0.82 (95% confidence interval 0.38-1.56). The lung cancer incidence was not increased among the subway drivers. The study gives some evidence against the hypothesis that subway particles would be more potent in inducing lung cancer than particles in ambient air. (c) 2008 Wiley-Liss, Inc.

Exchange program. Alternative options for purchase of environmentally friendly vehicles in Stockholm

Energy Technology Data Exchange (ETDEWEB)

Rader Olsson, Amy [Inregia AB, Stockholm (Sweden); Elam, N. [Atrax Energi AB, Goeteborg (Sweden)

1999-11-01

The city of Stockholm has decided to exchange 300 of its gasoline-driven vehicles for vehicles which emit fewer hazardous pollutants. A vehicle exchange program is being developed based on analyses which describe the driving patterns of Stockholm's vehicles, alternative fuel technology status, and financing alternatives. This report comprises the first two analyses, that of Stockholm's fleet driving patterns and alternative fuel technology options. The report has four major sections: * a technical analysis of the status of certain fuels and vehicles, including prognoses of availability in Sweden and the future development potential of each. (electric, biogas, ethanol, RME), * a driving study, which identifies those vehicles currently in Stockholm's fleet which could be exchanged for alternatively-fueled vehicles, * an analysis of five purchase package alternatives, and * a location analysis, which describes the accessibility of vehicles in each alternative to alternative fuel refueling facilities in Stockholm. Given current prices and availability of the alternative fuels and vehicles studied, we recommend a high share of electric and biogas vehicles for purchases during 1997. The cost-effectiveness of different vehicle types in their reduction of various hazardous pollutants, may however change dramatically as prices and availability of vehicles changes and the market for alternative fuels develops. Accessibility to alternative fuel refueling facilities is adequate in Stockholm, though not always ideal. To improve the accessibility of biogas vehicles further, we suggest a third biogas refueling facility in the city's northeastern area (Ropsten, Vaertahamnen). If MFO chooses to purchase a significant number of diesel passenger vehicles to be driven on RME; we propose that a facility in the northeastern area would improve accessibility more than another facility in southern Stockholm.

PECAM-1 gene polymorphism (rs668 and subclinical markers of carotid atherosclerosis in patients with type 2 diabetes mellitus

Directory of Open Access Journals (Sweden)

Popović D

2016-06-01

Full Text Available The platelet endothelial cell adhesion molecule 1 (PECAM-1 plays an important role in many inflammatory processes, including the development of atherosclerosis. Polymorphism rs668 of the PECAM-1 gene (373C/G is functional, and it was reported to be associated with increased serum levels of PECAM-1. We investigated the association between the rs668 polymorphism of PECAM-1 and subclinical markers of carotid atherosclerosis in subjects with type 2 diabetes mellitus (T2DM. Five hundred and ninety-five T2DM subjects and 200 control subjects were enrolled. The carotid intima-media thickness (CIMT and plaque characteristics (presence and structure were assessed ultrasonographically. Biochemical analyses were performed using standard biochemical methods. Geno-typing of the PECAM-1 gene polymorphism (rs668 was performed using KASPar assays. The control examinations were performed 3.8 ± 0.5 years after the initial examination. Higher CIMT was found in patients with T2DM in comparison with subjects without T2DM. Statistically sig-nificantly faster progression of the atherosclerotic markers was shown in subjects with T2DM in comparison with the control group. When adjusted to other risk factors, the rs668 GG genotype was associated with an increased risk of carotid plaques in subjects with T2DM. We concluded that our study demonstrated a minor effect of the rs668 PECAM-1 on markers of carotid atherosclerosis in subjects with T2DM.

Emerging Roles of Tumor Necrosis Factor-Stimulated Gene-6 in the Pathophysiology and Treatment of Atherosclerosis

Directory of Open Access Journals (Sweden)

Rena Watanabe

2018-02-01

Full Text Available Tumor necrosis factor-stimulated gene-6 (TSG-6 is a 35-kDa glycoprotein that has been shown to exert anti-inflammatory effects in experimental models of arthritis, acute myocardial infarction, and acute cerebral infarction. Several lines of evidence have shed light on the pathophysiological roles of TSG-6 in atherosclerosis. TSG-6 suppresses inflammatory responses of endothelial cells, neutrophils, and macrophages as well as macrophage foam cell formation and vascular smooth muscle cell (VSMC migration and proliferation. Exogenous TSG-6 infusion and endogenous TSG-6 attenuation with a neutralizing antibody for four weeks retards and accelerates, respectively, the development of aortic atherosclerotic lesions in ApoE-deficient mice. TSG-6 also decreases the macrophage/VSMC ratio (a marker of plaque instability and promotes collagen fibers in atheromatous plaques. In patients with coronary artery disease (CAD, plasma TSG-6 levels are increased and TSG-6 is abundantly expressed in the fibrous cap within coronary atheromatous plaques, indicating that TSG-6 increases to counteract the progression of atherosclerosis and stabilize the plaque. These findings indicate that endogenous TSG-6 enhancement and exogenous TSG-6 replacement treatments are expected to emerge as new lines of therapy against atherosclerosis and related CAD. Therefore, this review provides support for the clinical utility of TSG-6 in the diagnosis and treatment of atherosclerotic cardiovascular diseases.

Renovation of the Stockholm sewerage system

International Nuclear Information System (INIS)

Sandin, Paer

1987-01-01

Within a few years Stockholm will let all its treated wastewater into the Saltsjoen. The Saltsjoen is the inner part of the Stockholm Archipelago, which is one of the finest recreation areas in Sweden and where many Stockholmians spend a great deal of their leisure time. That is one reason why it is so important that all wastewater is treated before it reaches the recipient. A sewerage system in bad condition means that the risk of not allowed/unplanned overflows is increased. In order to prevent overflows we drafted 'Plan 83' which tells us how our sewerage system shall be constructed in the future and what measures has to be made in the system. Renovations of the existing pipes is one method to get a well functioning sewer system. Today we have made about 50 different objects at a total length of 6000 m. Why do we renovate sewers and why are we attempting to develop methods for pipe renovations?

Stockholm CHP potential - An opportunity for CO2 reductions?

International Nuclear Information System (INIS)

Danestig, Maria; Gebremehdin, Alemayehu; Karlsson, Bjoern

2007-01-01

The potential for combined heat and power (CHP) generation in Stockholm is large and a total heat demand of about 10 TWh/year can be met in a renewed large district heating system. This model of the Stockholm district heating system shows that CHP generation can increase from 8% in 2004 to 15.5% of the total electricity generation in Sweden. Increased electricity costs in recent years have awakened an interest to invest in new electricity generation. Since renewable alternatives are favoured by green certificates, bio-fuelled CHP is most profitable at low electricity prices. Since heat demand in the district heating network sets the limit for possible electricity generation, a CHP alternative with a high electricity to heat ratio will be more profitable at when electricity prices are high. The efficient energy use in CHP has the potential to contribute to reductions in carbon dioxide emissions in Europe, when they are required and the European electricity market is working perfectly. The potential in Stockholm exceeds Sweden's undertakings under the Kyoto protocol and national reduction goals. (author)

Erik Gunnar Asplund’s Stockholm Public Library

DEFF Research Database (Denmark)

Andersen, Michael Asgaard

2017-01-01

Stockholm Public Library, which opened on March 31, 1928, was in many ways an innovation in the Nordic countries. Most striking was the fact that lenders could now take books off the shelves themselves, but the central placement of the lending room and the secondary placement of the reading rooms...... also indicated a new way to do libraries. The thoughts embodied in the building became a model for many later libraries. The building is not only testimony to an important period of Nordic architectural history and a recognized masterpiece by the Swedish architect Erik Gunnar Asplund (1885......–1940), it is also part of the history of the Nordic social model that was taking shape in the interwar years. By its function as a public institution and its unique architectural qualities, Stockholm Public Library today stands as an important work of Nordic welfare building....

Substance Flow Analyses of Organic Pollutants in Stockholm

International Nuclear Information System (INIS)

Jonsson, A.; Friden, U.; Thuresson, K.; Soerme, L.

2008-01-01

This paper summarizes substance flow analyses for four organic substances in the City of Stockholm, Sweden: diethylhexyl phthalate (DEHP), alkylphenolethoxylates (APEO), polybrominated diphenylethers (PBDE) and chlorinated paraffins (CP). The results indicate that the stocks of APEO, PBDE and CP all are approximately 200-250 tonnes, whereas the DEHP stock is two orders of magnitude larger. Emissions can be linked to imported consumer goods such as electronics (PBDE) and textiles (APEO), and to construction materials (DEHP, CP). For several of the substances considerable amounts remain in the technosphere for a long time, even after use of the substance in new products has been eliminated. For example, the use of DEHP as plasticizer for PVC plastics in cables and floorings has more or less been phased-out, but still these applications make up a stock of some 20,000 tonnes (85% of the total DEHP stock in Stockholm) and emit 28 tonnes of DEHP annually (93% of overall emissions). Likewise, the use of chlorinated paraffins in sealants has been radically reduced, but there are 170 tonnes of CP in sealants in Stockholm making up 75% of the stock, and causing half of the emissions to water and air. These emissions are likely to continue for decades, and the stocks therefore have to be considered when analysing and managing the impact of urban substance flows on the environment

(18)F-FDG PET imaging of murine atherosclerosis

DEFF Research Database (Denmark)

Hag, Anne Mette Fisker; Pedersen, Sune Folke; Christoffersen, Christina

2012-01-01

To study whether (18)F-FDG can be used for in vivo imaging of atherogenesis by examining the correlation between (18)F-FDG uptake and gene expression of key molecular markers of atherosclerosis in apoE(-/-) mice....

EMS – Elektron Musik Studion in Stockholm

DEFF Research Database (Denmark)

Groth, Sanne Krogh

2016-01-01

In 1964 the electronic music studio EMS, Stockholm opened as a conventional analogue studio. The primary intension with the institution was to build the world’s most advanced hybrid studio and to conduct an international research program into sound and sound perception. With financial support from...

Abundance and composition of near surface microplastics and plastic debris in the Stockholm Archipelago, Baltic Sea.

Science.gov (United States)

Gewert, Berit; Ogonowski, Martin; Barth, Andreas; MacLeod, Matthew

2017-07-15

We collected plastic debris in the Stockholm Archipelago using a manta trawl, and additionally along a transect in the Baltic Sea from the island of Gotland to Stockholm in a citizen science study. The samples were concentrated by filtration and organic material was digested using hydrogen peroxide. Suspected plastic material was isolated by visual sorting and 59 of these were selected to be characterized with Fourier transform infrared spectroscopy. Polypropylene and polyethylene were the most abundant plastics identified among the samples (53% and 24% respectively). We found nearly ten times higher abundance of plastics near central Stockholm than in offshore areas (4.2×10 5 plastics km -2 compared to 4.7×10 4 plastics km -2 ). The abundance of plastic debris near Stockholm was similar to urban areas in California, USA, and the overall abundance in the Stockholm Archipelago was similar to plastic abundance reported in the northwestern Mediterranean Sea. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Phytosterols and atherosclerosis

DEFF Research Database (Denmark)

Schrøder, Malene

Cardiovascular disease (CVD) is the major cause of premature deaths worldwide. Coronary heart disease is the most common CVD, caused by atherosclerosis in the coronary arteries. Atherosclerosis is a multifactorial disease influenced by both genetic and environmental factors. WHO has in 2007 listed...... in its “Guidelines for assessment and management of cardiovascular risk” the following risk factors to influence progressive atherosclerosis: hypertension, abnormal blood lipids, diabetes, unhealthy diet, physical inactivity and smoking. Phytosterols (plant sterols and plant stanols) are known...... their blood cholesterol levels. The aim of this Ph.D. project was to investigate the effects of phytosterols on the development of atherosclerosis in the aorta of heterozygous Watanabe Heritable Hyperlipidemic (WHHL) rabbits. The main advantage of animal studies to human studies in atherosclerosis research...

SMAD3 rs17228212 gene polymorphism is associated with reduced risk to cerebrovascular accidents and subclinical atherosclerosis in anti-CCP negative Spanish rheumatoid arthritis patients.

Science.gov (United States)

García-Bermúdez, Mercedes; López-Mejías, Raquel; Genre, Fernanda; Castañeda, Santos; González-Juanatey, Carlos; Llorca, Javier; Corrales, Alfonso; Miranda-Filloy, José A; Rueda-Gotor, Javier; Gómez-Vaquero, Carmen; Rodríguez-Rodríguez, Luis; Fernández-Gutiérrez, Benjamín; Pascual-Salcedo, Dora; Balsa, Alejandro; López-Longo, Francisco J; Carreira, Patricia; Blanco, Ricardo; González-Álvaro, Isidoro; Martín, Javier; González-Gay, Miguel A

2013-01-01

Rheumatoid arthritis (RA) is a complex polygenic inflammatory disease associated with accelerated atherosclerosis and increased risk of cardiovascular (CV) disease. Previous genome-wide association studies have described SMAD3 rs17228212 polymorphism as an important signal associated with CV events. The aim of the present study was to evaluate for the first time the relationship between this gene polymorphism and the susceptibility to CV manifestations and its potential association with the presence of subclinical atherosclerosis assessed by the evaluation of carotid intima-media thickness (cIMT) in patients with RA. One thousand eight hundred and ninety-seven patients fulfilling classification criteria for RA were genotyped for SMAD3 rs17228212 gene polymorphism through TaqMan genotyping assay. Also, subclinical atherosclerosis determined by the assessment of cIMT was analyzed in a subgroup of these patients by carotid ultrasonography. No statistically significant differences were observed when allele frequencies of RA patients with or without CV events were compared. Nevertheless, when RA patients were stratified according to anti-cyclic citrullinated peptide (anti-CCP) status, we found that in RA patients who were negative for anti-CCP antibodies, the presence of C allele of SMAD3 rs17228212 polymorphism conferred a protective effect against the risk of cerebrovascular accident (CVA) after adjustment for demographic and classic CV risk factors (HR [95%CI]=0.36 [0.14-0.94], p=0.038) in a Cox regression model. Additionally, correlation between the presence of C allele of SMAD3 rs17228212 polymorphism and lower values of cIMT was found after adjustment for demographic and classic CV risk factors (p-value=0.0094) in the anti-CCP negative RA patients. Our results revealed that SMAD3 rs17228212 gene variant is associated with lower risk of CVA and less severe subclinical atherosclerosis in RA patients negative for anti-CCP antibodies. These findings may have

SMAD3 rs17228212 gene polymorphism is associated with reduced risk to cerebrovascular accidents and subclinical atherosclerosis in anti-CCP negative Spanish rheumatoid arthritis patients.

Directory of Open Access Journals (Sweden)

Mercedes García-Bermúdez

Full Text Available Rheumatoid arthritis (RA is a complex polygenic inflammatory disease associated with accelerated atherosclerosis and increased risk of cardiovascular (CV disease. Previous genome-wide association studies have described SMAD3 rs17228212 polymorphism as an important signal associated with CV events. The aim of the present study was to evaluate for the first time the relationship between this gene polymorphism and the susceptibility to CV manifestations and its potential association with the presence of subclinical atherosclerosis assessed by the evaluation of carotid intima-media thickness (cIMT in patients with RA.One thousand eight hundred and ninety-seven patients fulfilling classification criteria for RA were genotyped for SMAD3 rs17228212 gene polymorphism through TaqMan genotyping assay. Also, subclinical atherosclerosis determined by the assessment of cIMT was analyzed in a subgroup of these patients by carotid ultrasonography.No statistically significant differences were observed when allele frequencies of RA patients with or without CV events were compared. Nevertheless, when RA patients were stratified according to anti-cyclic citrullinated peptide (anti-CCP status, we found that in RA patients who were negative for anti-CCP antibodies, the presence of C allele of SMAD3 rs17228212 polymorphism conferred a protective effect against the risk of cerebrovascular accident (CVA after adjustment for demographic and classic CV risk factors (HR [95%CI]=0.36 [0.14-0.94], p=0.038 in a Cox regression model. Additionally, correlation between the presence of C allele of SMAD3 rs17228212 polymorphism and lower values of cIMT was found after adjustment for demographic and classic CV risk factors (p-value=0.0094 in the anti-CCP negative RA patients.Our results revealed that SMAD3 rs17228212 gene variant is associated with lower risk of CVA and less severe subclinical atherosclerosis in RA patients negative for anti-CCP antibodies. These findings may have

Weight-loss changes PPAR expression, reduces atherosclerosis and improves cardiovascular function in obese insulin-resistant mice

Energy Technology Data Exchange (ETDEWEB)

Verreth, Wim; Verhamme, Peter; Pelat, Michael; Ganame, Javier; Bielicki, John K.; Mertens, Ann; Quarck, Rozenn; Benhabiles, Nora; Marguerie, Gerard; Mackness, Bharti; Mackness, Mike; Ninio, Ewa; Herregods, Marie-Christine; Balligand, Jean-Luc; Holvoet, Paul

2003-09-01

Weight-loss in obese insulin-resistant, but not in insulin-sensitive, persons reduces CHD risk. It is not known to what extent changes in the adipose gene expression profile are important for reducing CHD risk. We studied the effect of diet restriction-induced weight-loss on gene expression in adipose tissue, atherosclerosis and cardiovascular function in mice with combined leptin and LDL-receptor deficiency. Obesity, hypertriglyceridemia and insulin-resistance are associated with hypertension, impaired left ventricle function and accelerated atherosclerosis in those mice. Diet restriction during 12 weeks caused a 45% weight-loss and changes in the gene expression in adipose tissue of PPARa and PPAR? and of key genes regulating glucose transport and insulin sensitivity, lipid metabolism, oxidative stress and inflammation, most of which are under the transcriptional control of PPARs. These changes were associated with increased insulin-sensitivity, decreased hypertriglyceridemia, reduced mean 24-hour blood pressure and heart rate, restored circadian variations of blood pressure and heart rate, increased ejection fraction, and reduced atherosclerosis. Thus, induction of PPARa and PPAR? in adipose tissue is a key mechanism for reducing atherosclerosis and improving cardiovascular function resulting from weight-loss. Our observations point to the critical role of PPARs in the pathogenesis of cardiovascular features of the metabolic syndrome.

Raid, Kaljo: Symphony No. 2, "Stockholm" / Guy S. Rickards

Index Scriptorium Estoniae

Rickards, Guy S.

1996-01-01

Uuest heliplaadist "Raid, Kaljo: Symphony No. 2, "Stockholm"; Tubin, Eduard: Elegy for Strings (arr. Raid). Symphony No. 11 (orch. Raid). Estonian State Symphony Orchestra, Arvo Volmer". Koch International Classics 37291-2 (48 minutes:DDD)

Fluxes of 13 selected pharmaceuticals in the water cycle of Stockholm, Sweden.

Science.gov (United States)

Wahlberg, C; Björlenius, B; Paxéus, N

2011-01-01

Mass flows of 13 pharmaceutical active ingredients (APIS) found in drinking water were studied in the water cycle of Stockholm. Data were collected by analyzing samples of surface water, raw water and drinking water as well as influents, effluents and sludges from waste water treatment plants (WWTPs) in Stockholm area. A mass balance was performed, based on sold amounts of pharmaceuticals and the measured concentrations in water and sludge. The selected APls were all present in WWTP effluents and the removal rates for many of them were poor. Mass balance calculations showed that the three studied WWTPs in Stockholm release considerable amounts of the selected APIs into the Baltic Sea while the portions ending up in WWTP sludge were significantly lower. The levels of APIs found in drinking water are low at present, but may increase in the future unless the releases from WWTPs in the catchment of Lake Mälären are mitigated.

Nanoparticles containing a liver X receptor agonist inhibit inflammation and atherosclerosis.

Science.gov (United States)

Zhang, Xue-Qing; Even-Or, Orli; Xu, Xiaoyang; van Rosmalen, Mariska; Lim, Lucas; Gadde, Suresh; Farokhzad, Omid C; Fisher, Edward A

2015-01-28

Liver X receptor (LXR) signaling pathways regulate lipid metabolism and inflammation, which has generated widespread interest in developing synthetic LXR agonists as potential therapeutics for the management of atherosclerosis. In this study, it is demonstrated that nanoparticles (NPs) containing the synthetic LXR agonist GW3965 (NP-LXR) exert anti-inflammatory effects and inhibit the development of atherosclerosis without causing hepatic steatosis. These NPs are engineered through self-assembly of a biodegradable diblock poly(lactide-co-glycolide)-b-poly(ethylene glycol) (PLGA-b-PEG) copolymer. NP-LXR is significantly more effective than free GW3965 at inducing LXR-target gene expression and suppressing inflammatory factors in macrophages in vitro and in vivo. Additionally, the NPs elicit negligible lipogenic gene stimulation in the liver. Using the Ldlr (-/-) mouse model of atherosclerosis, abundant colocalization of fluorescently labeled NPs within plaque macrophages following systemic administration is seen. Notably, six intravenous injections of NP-LXR over 2 weeks markedly reduce the CD68-positive cell (macrophage) content of plaques (by 50%) without increasing total cholesterol or triglycerides in the liver and plasma. Together, these findings identify GW3965-encapsulated PLGA-b-PEG NPs as a promising nanotherapeutic approach to combat atherosclerosis, providing the benefits of LXR agonists without their adverse effects on hepatic and plasma lipid metabolism. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Stockholm Shines (Editorial

Directory of Open Access Journals (Sweden)

Denise Koufogiannakis

2009-09-01

Full Text Available I didn’t sleep much in Stockholm. The eight hour time difference and the jet lag completely messed me up, not to mention the 19 hours of daylight! But during the day when I was so tired, the content being presented at the conference and the people I met kept me buzzing and wide awake! It is always nice to find a group of people who are interested in the same things as you are, and to do so in a beautiful setting with great food and a friendly environment is all the better. In my opinion, the 5th EBLIP conference was the best yet! I returned to Canada inspired and intellectually stimulated.The EBLIP conference is one of the few times that those of us who work on the EBLIP journal have a chance to get together and talk in person. Our journal editors are situated in the U.K., Canada, and the United States, so our work is done primarily via e‐mail and the occasional conference call. Three of us made it to Stockholm (Alison, Lorie and myself, so it was great to touch base in person and have a drink or two together! We also got to see several members of the Editorial Advisory board, as well as those who write evidence summaries for us, or are involved in some other way. Meeting some of these people in person for the first time after a lengthy e‐mail relationship is quite a treat! The Editors took the opportunity at the conference to hold a user group meeting, inviting anyone who was interested to attend and provide us with feedback about the journal. To start we provided an update, which included the fact that the journal has over 2000 registered readers. Did you know that in just one month (May 25 – June 24, 2009 we had 4649 site visits; 3,678 of them unique? Most visits to the journal are from the United States, followed by Canada, Australia, and the U.K. But we have people accessing the journal from all over world, and now that we are tracking site traffic via Google Analytics, it is easy to see on a map where our readers reside. There was

Inflammasomes and Atherosclerosis

Directory of Open Access Journals (Sweden)

S. Vallurupalli, MD

2016-09-01

Full Text Available Inflammation plays an important role in atherosclerosis. Inflammasomes play a crucial role in innate immunity, which mediates the body’s response to various pathogens. Of the different types of inflammasomes, NLRP3 has been implicated in atherosclerosis through the production of proinflammatory cytokines, IL-1β and IL-18. This review describes the role of the NLRP3 inflammasome in atherosclerosis and discusses potential therapeutic targets in the inflammasome pathway.

MARITICIDE AND THE STOCKHOLM SYNDROME. THE PROFILE OF WOMAN IMPRISONED FOR MARITICIDE

Directory of Open Access Journals (Sweden)

RALUCA PAVEL

2016-01-01

Full Text Available This study analyzes the correlation between female crime and Stockholm syndrome. Due to the fact that researchers focused in their studies on crimes committed by men, criminologists, sociologists and psychologists concentrated little time and attention to the female crime phenomenon. In this article I focused on the sociological interpretation of the results obtained by participant observation, an interview and a questionnaire on the Stockholm syndrome, applied to a number of 25 women imprisoned in Târgşor Prison for the murdering of their partner

[Features of allele polymorphism of genes involved in homocysteine and folate metabolism in patients with atherosclerosis of the lower extremity arteries].

Science.gov (United States)

Klenkova, N A; Kapustin, S I; Saltykova, N B; Shmeleva, V M; Blinov, M N

2009-01-01

Under study were features of allele polymorphism of genes of methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), methionine synthase (MS A 2756G), methionine synthase reductase (MTRR A66G) and methylenetetrahydrofolate dehydrogenase (MTHFD G1958A) in patients with atherosclerosis of the lower extremity arteries (ALEA). Patients with hyperhomocysteinemia (HHcy) had statistically significant increase of allele MTHFR 677T and MTRR 66GG as compared both with the control group and with the group of patients without HHcy. It suggests that polymorphism of genes involved in homocystein and folate metabolism might affect the risk of HHcy in patients with ALEA.

Letter from Stockholm.

Science.gov (United States)

Johansson, Per Magnus

2015-04-01

Some of the ideas of Sigmund Freud were preceded in a literary form by the Swedish writer August Strindberg in the late 19th century. Psychoanalysis itself was introduced in Sweden about a decade into the 20th century by two rivalling pioneers, the doctors Emanuel af Geijerstam and Poul Bjerre. After a slow start, the Danish-Norwegian Psychoanalytical Society and the Finnish-Swedish Psychoanalytical Society were formed in 1934 in Stockholm. The same year, Ericastiftelsen [The Erica Foundation], a psychotherapeutic clinic for children, was founded by Hanna Bratt. Five years later, in 1939, also in Stockholm, the organization that was to become St. Lukasstiftelsen [The Saint Luke's Foundation] was founded. It has been, and still is, an association that has trained psychodynamic psychotherapists, with a focus on existential, religious and philosophical questions. Today, St. Luke's tries to be up-dated from an academic standpoint. During the Second World War, several important psychoanalysts came to Sweden, for example René de Monchy, Lajos and Edith Székely, and Stefi Pedersen. Ola Andersson's doctoral dissertation ("Studies in the Prehistory of Psychoanalysis", 1962) and the historian Gunnar Brandell's essay ("Freud, a Man of His Century", 1961) have had an international impact. In the last two decades, an authorized and carefully edited translation of Freud's collected works has been published by Natur och Kultur, and the history of psychoanalysis in Sweden has been written at the University of Gothenburg. As a result of a recent interest in the work of Jacques Lacan, and French psychoanalysis, philosophy and literature, the journal Psykoanalytisk Tid/Skrift was founded in 2002, in Gothenburg. Since 2011 the journal is called Arche. The largest organized group of psychoanalysts in Sweden today is the Swedish Psychoanalytical Association (SPAF), which has around 225 members. Since 2008, it no longer has the right to license psychotherapists, a situation which

Urban Metal Flows - A Case Study of Stockholm. Review and Conclusions

International Nuclear Information System (INIS)

Bergbaeck, B.; Johansson, K.; Mohlander, U.

2001-01-01

Metals have rapidly accumulated in the anthroposphere, especially in urban areas, indicating possible environmental and resource problems. Here, Stockholm City was chosen for a case study of urban metal flows, i.e. metal inflow to, metals in the stock of,and metal outflow from the anthroposphere to the biosphere. The metal stock of Stockholm is large and still growing. The large amounts of metals in the solid waste fraction totally dominate the outflow from the city. For major parts of the stock, the emissions from goods in use are negligible. There are, however,goods applications corresponding to significant emissions: e.g. the traffic sector (Cu, Zn, Cr, Ni, Pb), the tapwater system (Cu), roofs/fronts or other metal surfaces (Cu, Zn). Today's known metal flows from the anthroposphere of Stockholm to the biosphere and sewage sludge are quantitatively dominated by Zn(34 ton y -1 ) and Cu (14 ton y -1 ). Historical and present emissions have resulted in high metal concentrations in sediments (especially Cd, Hg and Pb, but also Cu and Zn), groundwater (Cu, Hg) and in soils (Hg, Cu, Pb). At present the annual median concentrations are below the Swedish limits for metals in sewage sludge, even if the safety margins are small for Cd, Hg and to some extent Cu. The flows of Cu and Zn to Stockholm soils are high with a significant accumulation indicating an environmental impact in a longer time perspective.High levels of metals in surface sediments in the water environments reflects an ongoing input where these metals are transported from known (Cu, Zn) and or partly unknown (Cd, Hg, Pb) sources. In future urban areas, monitoring of metal flows must be performed both in the anthroposphere and the biospherein order to have a pro active approach to urban environmental problems and to get prompt answers to measures taken

TUG1 knockdown ameliorates atherosclerosis via up-regulating the expression of miR-133a target gene FGF1.

Science.gov (United States)

Zhang, Lei; Cheng, Hailing; Yue, Yuxia; Li, Shuangzhan; Zhang, Daping; He, Ruili

Long non-coding RNAs (lncRNAs) have been revealed to participate in the pathological events associated with atherosclerosis. However, the exact role of lncRNA taurine-up-regulated gene 1 (TUG1) and its possible molecular mechanism in atherosclerosis remain unidentified. High-fat diet (HFD)-treated ApoE -/- mice were used as an in vivo model of atherosclerosis. Ox-LDL-induced macrophages and vascular smooth muscle cells (VSMCs) were employed as cell models of atherosclerosis. qRT-PCR was performed to detect the expression of TUG1 and miR-133a. Serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were analyzed by commercially available enzyme kits. Oil red O and hematoxylin and eosin (H&E) staining were conducted to examine atherosclerotic lesion. Luciferase reporter assay combined with RNA immunoprecipitation (RIP) was applied to confirm the interaction between TUG1, miR-133a and FGF1. Cell proliferation ability was determined by Cell Counting Kit-8 (CCK-8) assay and trypan blue dye exclusion test. Cell apoptosis was evaluated with TUNEL assay. Expression and production of inflammatory cytokines was measured with western blot and ELISA analysis. TUG1 expression was up-regulated in HFD-treated ApoE -/- mice, as well as in ox-LDL-induced RAW264.7 and MOVAS cells. TUG1 knockdown inhibited hyperlipidemia, decreased inflammatory response, and attenuated atherosclerotic lesion in HFD-treated ApoE -/- mice. TUG1 could function as a molecular sponge of miR-133a to suppress its expression. TUG1 overexpression accelerated cell growth, improved inflammatory factor expression, and inhibited apoptosis in ox-LDL-stimulated RAW264.7 and MOVAS cells, while this effect was abated after transfection with miR-133 mimic. Moreover, fibroblast growth factor 1 (FGF1) was identified as a direct target of miR-133a. Restored expression of FGF1 overturned the effect of miR-133a on cell

Vaccination against atherosclerosis

NARCIS (Netherlands)

Es, Thomas van

2009-01-01

Atherosclerosis, the predominantly underlying pathology of cardiovascular events, is the consequence of lipid deposition in the arterial wall, mostly as consequence of high levels of serum cholesterol. Treatment of atherosclerosis is mainly focused at the reduction of cholesterol levels by lipid

PERSISTENT ORGANIC POLLUTANS (POPS DAN KONVENSI STOCKHOLM

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Lina Warlina

2010-07-01

Full Text Available Persistent organic pollutants (POPs are toxic chemicals that adversely affect human health and the environment around the world. Because they can be transported by wind and water, most POPs generated in one country can affect people and wildlife far from where they are used and released. They persist for long periods of time in the environment and can accumulate and pass from one species to the next through the food chain. To address this global concern, many countries in the world joined forces with 90 other countries and the European Community to sign a groundbreaking United Nations treaty in Stockholm, Sweden, in May 2001, known as the Stockholm Convention. One of important agreement is all countries agreed to reduce or eliminate the production, use, and/or release of 12 key POPs. The Convention specifies a scientific review process that could lead to the addition of other POPs chemicals of global concern. POPs include a range of substances that include intentionally produced chemicals currently or once used in agriculture, disease control, manufacturing, or industrial processes. Also it can be produced by unintentionally produced chemicals, such as dioxins, that result from some industrial processes and from combustion (for example, municipal and medical waste incineration and backyard burning of trash.

Hammarby Sjöstad in Stockholm a model case?

DEFF Research Database (Denmark)

Grønlund, Bo

2010-01-01

central government agencies have contributed to put these guidelines in practice. Representatives have also taken part in similar work at CEN in Brussels. In Sweden, the Stockholm Police started to work out guidelines and give advice - with the mixed new urban district Ärvinge near Kista as their primary...

The Data Acquisition System of the Stockholm Educational Air Shower Array

Science.gov (United States)

Hofverberg, P.; Johansson, H.; Pearce, M.; Rydstrom, S.; Wikstrom, C.

2005-12-01

The Stockholm Educational Air Shower Array (SEASA) project is deploying an array of plastic scintillator detector stations on school roofs in the Stockholm area. Signals from GPS satellites are used to time synchronise signals from the widely separated detector stations, allowing cosmic ray air showers to be identified and studied. A low-cost and highly scalable data acquisition system has been produced using embedded Linux processors which communicate station data to a central server running a MySQL database. Air shower data can be visualised in real-time using a Java-applet client. It is also possible to query the database and manage detector stations from the client. In this paper, the design and performance of the system are described

Hypoxia-Inducible Factor-1α Expression in Macrophages Promotes Development of Atherosclerosis

DEFF Research Database (Denmark)

Pedersen, Annemarie Aarup; Pedersen, Tanja X; Junker, Nanna

2016-01-01

transplanted with bone marrow from mice with HIF-1α deficiency in the myeloid cells or control bone marrow. The HIF-1α deficiency in myeloid cells reduced atherosclerosis in aorta of the Ldlr(-/-) recipient mice by ≈72% (P=0.006).In vitro, HIF-1α-deficient macrophages displayed decreased differentiation...... to proinflammatory M1 macrophages and reduced expression of inflammatory genes. HIF-1α deficiency also affected glucose uptake, apoptosis, and migratory abilities of the macrophages. CONCLUSIONS: HIF-1α expression in macrophages affects their intrinsic inflammatory profile and promotes development of atherosclerosis....

Monitoring of air pollution in Stockholm county. Results up to September 1999; Oevervakning av luftfoeroreningar i Stockholms laen. Resultat till och med september 1999

Energy Technology Data Exchange (ETDEWEB)

Akselsson, Cecilia [ed.

2000-05-01

Swedish Environmental Research Inst. have measured deposition of air pollutants, soil water quality, and air pollution levels in forested areas in different parts of Sweden. This report treats Stockholm county and the compilation covers the period 1992-1999, with more detailed monitoring for 1998-1999.

Telomerase Activation in Atherosclerosis and Induction of Telomerase Reverse Transcriptase Expression by Inflammatory Stimuli in Macrophages

Science.gov (United States)

Gizard, Florence; Heywood, Elizabeth B.; Findeisen, Hannes M.; Zhao, Yue; Jones, Karrie L.; Cudejko, Cèline; Post, Ginell R.; Staels, Bart; Bruemmer, Dennis

2010-01-01

Objective Telomerase serves as a critical regulator of tissue renewal. Although telomerase activity is inducible in response to various environmental cues, it remains unknown whether telomerase is activated during the inflammatory remodeling underlying atherosclerosis formation. To address this question, we investigated in the present study the regulation of telomerase in macrophages and during atherosclerosis development in LDL-receptor-deficient mice. Methods and Results We demonstrate that inflammatory stimuli activate telomerase in macrophages by inducing the expression of the catalytic subunit telomerase reverse transcriptase (TERT). Reporter and chromatin immunoprecipitation assays identified a previously unrecognized NF-κB response element in the TERT promoter, to which NF-κB is recruited during inflammation. Inhibition of NF-κB signaling completely abolished the induction of TERT expression, characterizing TERT as a bona fide NF-κB target gene. Furthermore, functional experiments revealed that TERT-deficiency results in a senescent cell phenotype. Finally, we demonstrate high levels of TERT expression in macrophages of human atherosclerotic lesions and establish that telomerase is activated during atherosclerosis development in LDL-receptor-deficient mice. Conclusion These results characterize TERT as a previously unrecognized NF-κB target gene in macrophages and demonstrate that telomerase is activated during atherosclerosis. This induction of TERT expression prevents macrophage senescence and may have important implications for the development of atherosclerosis. PMID:21106948

HIV-infection, atherosclerosis and the inflammatory pathway: candidate gene study in a Spanish HIV-infected population.

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Laura Ibáñez

Full Text Available BACKGROUND: Higher prevalence of atherosclerosis and higher cardiovascular risk is observed in HIV-infected individuals. The biological mechanisms underlying these processes are unclear. Several studies have implicated genetic variants in the inflammatory genes in cardiovascular disease and in HIV natural course infection. METHODS & FINDINGS: In this study we have tested the possible association between genetic variants in several inflammatory genes and asymptomatic cardiovascular disease measured by carotid intima media thickness (cIMT and atherosclerotic plaque presence as dependent variables in 213 HIV-infected individuals. A total of 101 genetic variants in 25 candidate genes have been genotyped. Results were analyzed using Plink and SPSS statistical packages. We have found several polymorphisms in the genes ALOX5 (rs2115819 p = 0.009, ALOX5AP (rs9578196 p = 0.007; rs4769873 p = 0.004 and rs9315051 p = 0.0004, CX3CL1 (rs4151117 p = 0.040 and rs614230 p = 0.015 and CCL5 (rs3817655 p = 0.018 and rs2107538 p = 0.018 associated with atherosclerotic plaque. cIMT mean has been associated with CRP (1130864 p = 0.0003 and rs1800947 p = 0.008, IL1RN (rs380092 p = 0.002 and ALOX5AP (rs3885907 p = 0.02 genetic variants. CONCLUSIONS: In this study we have found modest associations between genetic variants in several inflammatory genes and atherosclerotic plaque or cIMT. Nevertheless, our study adds evidence to the association between inflammatory pathway genetic variants and the atherosclerotic disease in HIV-infected individuals.

Episomal Nonviral Gene Therapy Vectors Slow Progression of Atherosclerosis in a Model of Familial Hypercholesterolemia

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Alastair G Kerr

2016-01-01

Full Text Available Familial hypercholesterolemia (FH is a life-threatening genetic disorder characterized by elevated levels of plasma low-density lipoprotein cholesterol (LDL-cholesterol. Current attempts at gene therapy for FH have been limited by the use of strong heterologous promoters which lack genomic DNA elements essential for regulated expression. Here, we have combined a minigene vector expressing the human LDLR cDNA from a 10 kb native human LDLR locus genomic DNA promoter element, with an efficient miRNA targeting 3-hydroxy-3-methylgutaryl-coenzyme A reductase (Hmgcr, to further enhance LDLR expression. We show that the combined vector suppresses endogenous Hmgcr transcripts in vivo, leading to an increase in LDLR transgene expression. In a diet-induced Ldlr-/- mouse model of FH, we show that administration of the combined vector reduces atherogenic plasma lipids by ≃32%. Finally, we demonstrate that our episomal nonviral vectors are able to reduce atherosclerosis by ≃40% after 12 weeks in vivo. Taken together, the vector system we describe exploits the normal cellular regulation of the LDLR to provide prolonged expression of LDLR through targeted knockdown of Hmgcr. This novel gene therapy system could act alone, or in synergy with current therapies that modulate intracellular cholesterol, such as statins, greatly enhancing its therapeutic application for FH.

Bolstering cholesteryl ester hydrolysis in liver: A hepatocyte-targeting gene delivery strategy for potential alleviation of atherosclerosis.

Science.gov (United States)

He, Hongliang; Lancina, Michael G; Wang, Jing; Korzun, William J; Yang, Hu; Ghosh, Shobha

2017-06-01

Current atherosclerosis treatment strategies primarily focus on limiting further cholesteryl esters (CE) accumulation by reducing endogenous synthesis of cholesterol in the liver. No therapy is currently available to enhance the removal of CE, a crucial step to reduce the burden of the existing disease. Given the central role of hepatic cholesteryl ester hydrolase (CEH) in the intrahepatic hydrolysis of CE and subsequent removal of the resulting free cholesterol (FC), in this work, we applied galactose-functionalized polyamidoamine (PAMAM) dendrimer generation 5 (Gal-G5) for hepatocyte-specific delivery of CEH expression vector. The data presented herein show the increased specific uptake of Gal-G5/CEH expression vector complexes (simply Gal-G5/CEH) by hepatocytes in vitro and in vivo. Furthermore, the upregulated CEH expression in the hepatocytes significantly enhanced the intracellular hydrolysis of high density lipoprotein-associated CE (HDL-CE) and subsequent conversion/secretion of hydrolyzed FC as bile acids (BA). The increased CEH expression in the liver significantly increased the flux of HDL-CE to biliary as well as fecal FC and BA. Meanwhile, Gal-G5 did not induce hepatic or renal toxicity. It was also not immunotoxic. Because of these encouraging pre-clinical testing results, using this safe and highly efficient hepatocyte-specific gene delivery platform to enhance the hepatic processes involved in cholesterol elimination is a promising strategy for the alleviation of atherosclerosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Single-Cell RNA-Seq Reveals the Transcriptional Landscape and Heterogeneity of Aortic Macrophages in Murine Atherosclerosis.

Science.gov (United States)

Cochain, Clément; Vafadarnejad, Ehsan; Arampatzi, Panagiota; Jaroslav, Pelisek; Winkels, Holger; Ley, Klaus; Wolf, Dennis; Saliba, Antoine-Emmanuel; Zernecke, Alma

2018-03-15

Rationale: It is assumed that atherosclerotic arteries contain several macrophage subsets endowed with specific functions. The precise identity of these subsets is poorly characterized as they ha ve been defined by the expression of a restricted number of markers. Objective: We have applied single-cell RNA-seq as an unbiased profiling strategy to interrogate and classify aortic macrophage heterogeneity at the single-cell level in atherosclerosis. Methods and Results: We performed single-cell RNA sequencing of total aortic CD45 + cells extracted from the non-diseased (chow fed) and atherosclerotic (11 weeks of high fat diet) aorta of Ldlr -/- mice. Unsupervised clustering singled out 13 distinct aortic cell clusters. Among the myeloid cell populations, Resident-like macrophages with a gene expression profile similar to aortic resident macrophages were found in healthy and diseased aortae, whereas monocytes, monocyte-derived dendritic cells (MoDC), and two populations of macrophages were almost exclusively detectable in atherosclerotic aortae, comprising Inflammatory macrophages showing enrichment in I l1b , and previously undescribed TREM2 hi macrophages. Differential gene expression and gene ontology enrichment analyses revealed specific gene expression patterns distinguishing these three macrophage subsets and MoDC, and uncovered putative functions of each cell type. Notably, TREM2 hi macrophages appeared to be endowed with specialized functions in lipid metabolism and catabolism, and presented a gene expression signature reminiscent of osteoclasts, suggesting a role in lesion calcification. TREM2 expression was moreover detected in human lesional macrophages. Importantly, these macrophage populations were present also in advanced atherosclerosis and in Apoe -/- aortae, indicating relevance of our findings in different stages of atherosclerosis and mouse models. Conclusions: These data unprecedentedly uncovered the transcriptional landscape and phenotypic

Functional promoter variant in zinc finger protein 202 predicts severe atherosclerosis and ischemic heart disease

DEFF Research Database (Denmark)

Frikke-Schmidt, R.; Nordestgaard, Børge; Grande, Peer

2008-01-01

Objectives This study was designed to test the hypotheses that single nucleotide polymorphisms ( SNPs), in zinc finger protein 202 ( ZNF202), predict severe atherosclerosis and ischemic heart disease ( IHD). Background ZNF202 is a transcriptional repressor controlling promoter elements in genes...... involved in vascular maintenance and lipid metabolism. Methods We first determined genotype association for 9 ZNF202 SNPs with severe atherosclerosis ( ankle brachial index >0.7 vs. ...,998 controls. Finally, we determined whether g. -660A>G altered transcriptional activity of the ZNF202 promoter in vitro. Results Cross-sectionally, ZNF202 g. -660 GG versus AA homozygosity predicted an odds ratio for severe atherosclerosis of 2.01 ( 95% confidence interval [CI]: 1.34 to 3.01). Prospectively...

Atherosclerosis-Driven Treg Plasticity Results in Formation of a Dysfunctional Subset of Plastic IFNγ+ Th1/Tregs.

Science.gov (United States)

Butcher, Matthew J; Filipowicz, Adam R; Waseem, Tayab C; McGary, Christopher M; Crow, Kevin J; Magilnick, Nathaniel; Boldin, Mark; Lundberg, Patric S; Galkina, Elena V

2016-11-11

Forkhead box P3 + T regulatory cells (Tregs) are key players in maintaining immune homeostasis. Evidence suggests that Tregs respond to environmental cues to permit or suppress inflammation. In atherosclerosis, Th1-driven inflammation affects Treg homeostasis, but the mechanisms governing this phenomenon are unclear. Here, we address whether atherosclerosis impacts Treg plasticity and functionality in Apoe - /- mice, and what effect Treg plasticity might have on the pathology of atherosclerosis. We demonstrate that atherosclerosis promotes Treg plasticity, resulting in the reduction of CXCR3 + Tregs and the accumulation of an intermediate Th1-like interferon (IFN)-γ + CCR5 + Treg subset (Th1/Tregs) within the aorta. Importantly, Th1/Tregs arise in atherosclerosis from bona fide Tregs, rather than from T-effector cells. We show that Th1/Tregs recovered from atherosclerotic mice are dysfunctional in suppression assays. Using an adoptive transfer system and plasticity-prone Mir146a -/- Tregs, we demonstrate that elevated IFNγ + Mir146a -/- Th1/Tregs are unable to adequately reduce atherosclerosis, arterial Th1, or macrophage content within Apoe -/- mice, in comparison to Mir146a +/+ Tregs. Finally, via single-cell RNA-sequencing and real-time -polymerase chain reaction, we show that Th1/Tregs possess a unique transcriptional phenotype characterized by coexpression of Treg and Th1 lineage genes and a downregulation of Treg-related genes, including Ikzf2, Ikzf4, Tigit, Lilrb4, and Il10. In addition, an ingenuity pathway analysis further implicates IFNγ, IFNα, interleukin-2, interleukin-7, CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), T-cell receptor, and Csnk2b-related pathways in regulating Treg plasticity. Atherosclerosis drives Treg plasticity, resulting in the accumulation of dysfunctional IFNγ + Th1/Tregs that may permit further arterial inflammation and atherogenesis. © 2016 American Heart Association, Inc.

Increased Hepatic Expression of Endothelial Lipase Inhibits Cholesterol Diet-Induced Hypercholesterolemia and Atherosclerosis in Transgenic Rabbits.

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Wang, Chuan; Nishijima, Kazutoshi; Kitajima, Shuji; Niimi, Manabu; Yan, Haizhao; Chen, Yajie; Ning, Bo; Matsuhisa, Fumikazu; Liu, Enqi; Zhang, Jifeng; Chen, Y Eugene; Fan, Jianglin

2017-07-01

Endothelial lipase (EL) is a key determinant in plasma high-density lipoprotein-cholesterol. However, functional roles of EL on the development of atherosclerosis have not been clarified. We investigated whether hepatic expression of EL affects plasma lipoprotein metabolism and cholesterol diet-induced atherosclerosis. We generated transgenic (Tg) rabbits expressing the human EL gene in the liver and then examined the effects of EL expression on plasma lipids and lipoproteins and compared the susceptibility of Tg rabbits with cholesterol diet-induced atherosclerosis with non-Tg littermates. On a chow diet, hepatic expression of human EL in Tg rabbits led to remarkable reductions in plasma levels of total cholesterol, phospholipids, and high-density lipoprotein-cholesterol compared with non-Tg controls. On a cholesterol-rich diet for 16 weeks, Tg rabbits exhibited significantly lower hypercholesterolemia and less atherosclerosis than non-Tg littermates. In Tg rabbits, gross lesion area of aortic atherosclerosis was reduced by 52%, and the lesions were characterized by fewer macrophages and smooth muscle cells compared with non-Tg littermates. Increased hepatic expression of EL attenuates cholesterol diet-induced hypercholesterolemia and protects against atherosclerosis. © 2017 American Heart Association, Inc.

Alcohol and atherosclerosis

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DA LUZ PROTASIO L.

2001-01-01

Full Text Available Atherosclerosis is manifested as coronary artery disease (CAD, ischemic stroke and peripheral vascular disease. Moderate alcohol consumption has been associated with reduction of CAD complications. Apparently, red wine offers more benefits than any other kind of drinks, probably due to flavonoids. Alcohol alters lipoproteins and the coagulation system. The flavonoids induce vascular relaxation by mechanisms that are both dependent and independent of nitric oxide, inhibits many of the cellular reactions associated with atherosclerosis and inflammation, such as endothelial expression of vascular adhesion molecules and release of cytokines from polymorphonuclear leukocytes. Hypertension is also influenced by the alcohol intake. Thus, heavy alcohol intake is almost always associated with systemic hypertension, and hence shall be avoided. In individuals that ingest excess alcohol, there is higher risk of coronary occlusion, arrhythmias, hepatic cirrhosis, upper gastrointestinal cancers, fetal alcohol syndrome, murders, sex crimes, traffic and industrial accidents, robberies, and psychosis. Alcohol is no treatment for atherosclerosis; but it doesn't need to be prohibited for everyone. Thus moderate amounts of alcohol (1-2 drinks/day, especially red wine, may be allowed for those at risk for atherosclerosis complications.

Hawthorn (Crataegus pinnatifida Bunge) leave flavonoids attenuate atherosclerosis development in apoE knock-out mice.

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Dong, Pengzhi; Pan, Lanlan; Zhang, Xiting; Zhang, Wenwen; Wang, Xue; Jiang, Meixiu; Chen, Yuanli; Duan, Yajun; Wu, Honghua; Xu, Yantong; Zhang, Peng; Zhu, Yan

2017-02-23

Hawthorn (Crataegus pinnatifida Bunge) leave have been used to treat cardiovascular diseases in China and Europe. Hawthorn leave flavonoids (HLF) are the main part of extraction. Whether hawthorn leave flavonoids could attenuate the development of atherosclerosis and the possible mechanism remain unknown. High-fat diet (HFD) mixed with HLF at concentrations of 5mg/kg and 20mg/kg were administered to apolipoprotein E (apoE) knock out mice. 16 weeks later, mouse serum was collected to determine the lipid profile while the mouse aorta dissected was prepared to measure the lesion area. Hepatic mRNA of genes involved in lipid metabolism were determined. Peritoneal macrophages were collected to study the impact of HLF on cholesterol efflux, formation of foam cell and the expression of ATP binding cassette transporter A1 (ABCA1). Besides, in vivo reverse cholesterol transport (RCT) was conducted. HLF attenuated the development of atherosclerosis that the mean atherosclerotic lesion area in en face aortas was reduced by 23.1% (Pflavonoids can slow down the development of atherosclerosis in apoE knockout mice via induced expression of genes involved in antioxidant activities, inhibition of the foam cell formation and promotion of RCT in vivo, which implies the potential use in the prevention of atherosclerosis. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Immune Response to Lipoproteins in Atherosclerosis

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Sonia Samson

2012-01-01

Full Text Available Atherosclerosis, the underlying cause of cardiovascular disease, is characterized by chronic inflammation and altered immune response. Cholesterol is a well-known risk factor associated with the development of cardiovascular diseases. Elevated serum cholesterol is unique because it can lead to development of atherosclerosis in animals and humans even in the absence of other risk factors. Modifications of low-density lipoproteins mediated by oxidation, enzymatic degradation, and aggregation result in changes in their function and activate both innate and adaptive immune system. Oxidized low-density lipoprotein (LDL has been identified as one of the most important autoantigens in atherosclerosis. This escape from self-tolerance is dependent on the formation of oxidized phospholipids. The emerging understanding of the importance of immune responses against oxidized LDL in atherosclerosis has focused attention on the possibility of development of novel therapy for atherosclerosis. This review provides an overview of immune response to lipoproteins and the fascinating possibility of developing an immunomodulatory therapy for atherosclerosis.

Atherosclerosis: Hypotheses and theories

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E. A. Yuryeva

2014-01-01

Full Text Available The article gives basic theories of the pathogenesis of atherosclerosis, including inflammatory, cholesterol, lipid, lipoprotein, iron ones, as a result of metabolic syndrome, oxidative stress. In spite of carefully and deeply developed and ongoing elaborated pathogenesis theories, the etiological factors of atherosclerosis remain unknown so far. The age-related aspect of the disease is discussed; atherosclerosis is considered to be a childhood-onset disease that manifests itself at a later age. The authors propose an experimental and clinical evidence-based concept of the common etiology of syndromes of atherosclerosis, namely: the body's endogenous intoxication that is permanent or periodically progressive may be a primary cause of altered conformation of different protein molecules with their higher ability to adsorb the trace elements consolidating the structural changes. This change of proteins diminishes their functions and determines their antigenic properties, which is attended by the development of different pathogenic components in relation to the body's individual features.

Temporal and spatial patterns of suicides in Stockholm's subway stations.

Science.gov (United States)

Uittenbogaard, Adriaan; Ceccato, Vania

2015-08-01

This paper investigates the potential temporal and spatial variations of suicides in subway stations in Stockholm, Sweden. The study also assesses whether the variation in suicide rates is related to the station environments by controlling for each station's location and a number of contextual factors using regression models and geographical information systems (GIS). Data on accidents are used as references for the analysis of suicides. Findings show that suicides tend to occur during the day and in the spring. They are concentrated in the main transportation hubs but, interestingly, during off-peak hours. However, the highest rates of suicides per passenger are found in Stockholm's subway stations located in the Southern outskirts. More than half of the variation in suicide rates is associated with stations that have walls between the two sides of the platform but still allow some visibility from passers-by. The surrounding environment and socioeconomic context show little effect on suicide rates, but stations embedded in areas with high drug-related crime rates tend to show higher suicide rates. Copyright © 2015 Elsevier Ltd. All rights reserved.

Detection of Marek's disease virus DNA in Japanese quail susceptible to atherosclerosis

International Nuclear Information System (INIS)

Pyrzak, R.; Shih, J.C.H.

1986-01-01

Marek's disease virus (MDV) was demonstrated as an etiological agent which causes atherosclerosis in the chicken. Since herpes viruses are ubiquitous, incidences of viral atherogenesis in humans and other animals were speculated. In this laboratory, the atherosclerosis susceptible (SUS) and resistant (RES) Japanese quail were developed as the animal model for atherosclerosis research. The susceptibility of the animal might be due to an infection of MDV or a related quail herpes virus (QHV). An initial attempt to isolate viruses from quail and an agar gel precipitin test for MDC were not positive. A DNA hybridization technique was used to determine whether the MDC-DNA existed in the quail cell. The gene library of MDV EcoRl DNA fragments was used to prepare the DNA probe, labeled with [ 32 P] by nick translation. Dot hybridizations were carried out by mixing the MDV-DNA probe with DNAs isolated from quail tissues. A high stringent condition was used. From this experiment it was found that the tissues from the SUS quail were hybridization positive, but most of them from RES quail were negative. When aortas were compared, the severe atherosclerotic had a strong hybridization (3-4 cop. of genome/cell) whereas the others hybridized moderately (1 cop./cell). It was concluded that genes from MDV or a QHV indeed existed in Japanese quail

Child mortality in Stockholm during 1885-1910

DEFF Research Database (Denmark)

Burström, B; Diderichsen, Finn; Smedman, L

1999-01-01

on the risk of measles death. Individual entries in a population-based register and on death certificates for children aged 0-15 years living in one parish in Stockholm in 1885, 1891, and 1910 (n = 36,718) were used to analyze cause-specific and overall death rates in relation to household size and the number...... crowding and the risk of death from pneumonia and bronchitis disappeared when controlling for other risk factors. A negative association between the risk of overall death and large household size became significantly positive when controlling for other risk factors. The increased risk of death from measles...

Modulation of ambient temperature promotes inflammation and initiates atherosclerosis in wild type C57BL/6 mice

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Daniel A. Giles

2016-11-01

Full Text Available Objectives: Obesity and obesity-associated inflammation is central to a variety of end-organ sequelae including atherosclerosis, a leading cause of death worldwide. Although mouse models have provided important insights into the immunopathogenesis of various diseases, modeling atherosclerosis in mice has proven difficult. Specifically, wild-type (WT mice are resistant to developing atherosclerosis, while commonly used genetically modified mouse models of atherosclerosis are poor mimics of human disease. The lack of a physiologically relevant experimental model of atherosclerosis has hindered the understanding of mechanisms regulating disease development and progression as well as the development of translational therapies. Recent evidence suggests that housing mice within their thermoneutral zone profoundly alters murine physiology, including both metabolic and immune processes. We hypothesized that thermoneutral housing would allow for augmentation of atherosclerosis induction and progression in mice. Methods: ApoE−/− and WT mice were housed at either standard (TS or thermoneutral (TN temperatures and fed either a chow or obesogenic “Western” diet. Analysis included quantification of (i obesity and obesity-associated downstream sequelae, (ii the development and progression of atherosclerosis, and (iii inflammatory gene expression pathways related to atherosclerosis. Results: Housing mice at TN, in combination with an obesogenic “Western” diet, profoundly augmented obesity development, exacerbated atherosclerosis in ApoE−/− mice, and initiated atherosclerosis development in WT mice. This increased disease burden was associated with altered lipid profiles, including cholesterol levels and fractions, and increased aortic plaque size. In addition to the mild induction of atherosclerosis, we similarly observed increased levels of aortic and white adipose tissue inflammation and increased circulating immune cell expression of pathways

Atherosclerosis in Watanabe heritable hyperlipidaemic rabbits. Evaluation by macroscopic, microscopic and biochemical methods and comparison of atherosclerosis variables

DEFF Research Database (Denmark)

Hansen, B F; Mortensen, A; Hansen, J F

1994-01-01

estimation of aortic atherosclerosis extent and by biochemical analysis of aortic cholesterol content. No noteworthy atherosclerosis was demonstrated within 19 months in heterozygous rabbits. In homozygous rabbits, atherosclerotic lesions were seen from the age of 4 months and progressed with age. All 19......-month-old rabbits had severe atherosclerotic disease. As much as 64% of the variation in atherosclerosis extent/severity could be explained by serum cholesterol and age. A highly significant correlation between the various methods for quantitation of atherosclerosis extent and/or severity...... was demonstrated, suggesting that quantitative microscopy, macroscopic morphometry and determination of aortic cholesterol content may be equally valid as a measure of atherosclerosis in WHHL rabbits and are therefore interchangeable....

Chronic Intermittent Hypoxia Induces Atherosclerosis

OpenAIRE

Savransky, Vladimir; Nanayakkara, Ashika; Li, Jianguo; Bevans, Shannon; Smith, Philip L.; Rodriguez, Annabelle; Polotsky, Vsevolod Y.

2007-01-01

Rationale: Obstructive sleep apnea, a condition leading to chronic intermittent hypoxia (CIH), is associated with hyperlipidemia, atherosclerosis, and a high cardiovascular risk. A causal link between obstructive sleep apnea and atherosclerosis has not been established.

Tofacitinib ameliorates atherosclerosis and reduces foam cell formation in apoE deficient mice.

Science.gov (United States)

Wang, Zaicun; Wang, Shumei; Wang, Zunzhe; Yun, Tiantian; Wang, Chenchen; Wang, Huating

2017-08-19

Atherosclerosis is a chronic inflammatory cardiovascular disease with high mortality worldwide. Tofacitinib (CP-690,550), an oral small-molecule Janus kinase inhibitor, has been shown to be effective in the treatment of rheumatoid arthritis, autoimmune encephalomyelitis and ulcerative colitis. However, its protective effect against atherosclerosis remains poorly understood. The aim of the present study was to evaluate the effects of Tofacitinib on atherogenic diet (ATD)-induced atherosclerosis using apolipoprotein E deficient (apoE-/-) mice. Atherosclerosis-prone apoE-/- mice were fed with ATD and treated with or without Tofacitinib through intragastrical administration (10 mg kg -1 day -1 ) for 8 weeks. Our results showed that Tofacitinib did not change plasma lipids, while significantly reduced the levels of plasma pro-inflammatory cytokines IL-6 and TNF-α. It also significantly attenuated atherosclerotic plaque lesion in the aortic root and macrophages contained in plaque as shown with Mac2 immuno-staining. Peritoneal macrophages (PMC) were separated from apoE-/- mice fed with 8-week ATD, and then subjected to inflammation tests. Flow cytometry analysis of F4/80 and CD206 and mRNA levels of M1 and M2 macrophages markers showed that M1 macrophages decreased while M2 macrophages increased in Tofacitinib treated group. Expressions of other inflammatory genes also indicated an anti-inflammatory status in mice treated with Tofacitinib. Ox-LDL was used to induce foam cell formation from PMC in wild type mice, and the results displayed a reduced formation of foam cells and decreased inflammation in mice with Tofacitinib administration (1 μM). The mRNA and protein levels of ATP binding cassette subfamily A member 1 (ABCA1), a key gene involved in cholesterol efflux, remarkably increased, while it was absence of alterations in scavenger receptors expression. Therefore, we demonstrated that Tofacitinib could attenuate atherosclerosis and foam cells formation by

Neighborhood characteristics influence DNA methylation of genes involved in stress response and inflammation: The Multi-Ethnic Study of Atherosclerosis.

Science.gov (United States)

Smith, Jennifer A; Zhao, Wei; Wang, Xu; Ratliff, Scott M; Mukherjee, Bhramar; Kardia, Sharon L R; Liu, Yongmei; Roux, Ava V Diez; Needham, Belinda L

2017-08-01

Living in a disadvantaged neighborhood is associated with poor health outcomes even after accounting for individual-level socioeconomic factors. The chronic stress of unfavorable neighborhood conditions may lead to dysregulation of the stress reactivity and inflammatory pathways, potentially mediated through epigenetic mechanisms such as DNA methylation. We used multi-level models to examine the relationship between 2 neighborhood conditions and methylation levels of 18 genes related to stress reactivity and inflammation in purified monocytes from 1,226 participants of the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based sample of US adults. Neighborhood socioeconomic disadvantage, a summary of 16 census-based metrics, was associated with DNA methylation [False discovery rate (FDR) q-value ≤ 0.1] in 2 out of 7 stress-related genes evaluated (CRF, SLC6A4) and 2 out of 11 inflammation-related genes (F8, TLR1). Neighborhood social environment, a summary measure of aesthetic quality, safety, and social cohesion, was associated with methylation in 4 of the 7 stress-related genes (AVP, BDNF, FKBP5, SLC6A4) and 7 of the 11 inflammation-related genes (CCL1, CD1D, F8, KLRG1, NLRP12, SLAMF7, TLR1). High socioeconomic disadvantage and worse social environment were primarily associated with increased methylation. In 5 genes with significant associations between neighborhood and methylation (FKBP5, CD1D, F8, KLRG1, NLRP12), methylation was associated with gene expression of at least one transcript. These results demonstrate that multiple dimensions of neighborhood context may influence methylation levels and subsequent gene expression of stress- and inflammation-related genes, even after accounting for individual socioeconomic factors. Further elucidating the molecular mechanisms underlying these relationships will be important for understanding the etiology of health disparities.

Cyanotic congenital heart disease and atherosclerosis.

Science.gov (United States)

Tarp, Julie Bjerre; Jensen, Annette Schophuus; Engstrøm, Thomas; Holstein-Rathlou, Niels-Henrik; Søndergaard, Lars

2017-06-01

Improved treatment options in paediatric cardiology and congenital heart surgery have resulted in an ageing population of patients with cyanotic congenital heart disease (CCHD). The risk of acquired heart disease such as atherosclerosis increases with age.Previous studies have speculated whether patients with CCHD are protected against atherosclerosis. Results have shown that the coronary arteries of patients with CCHD are free from plaques and stenosis. Decreased carotid intima-media thickness and low total plasma cholesterol may indicate a reduced risk of later development of atherosclerosis. However, the evidence is still sparse and questionable, and a reasonable explanation for the decreased risk of developing atherosclerosis in patients with CCHD is still missing.This review provides an overview of what is known about the prevalence and potential causes of the reduced risk of atherosclerosis in patients with CCHD. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Does high C-reactive protein concentration increase atherosclerosis? The Whitehall II Study.

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Mika Kivimäki

Full Text Available BACKGROUND: C-reactive protein (CRP, a marker of systemic inflammation, is associated with risk of coronary events and sub-clinical measures of atherosclerosis. Evidence in support of this link being causal would include an association robust to adjustments for confounders (multivariable standard regression analysis and the association of CRP gene polymorphisms with atherosclerosis (Mendelian randomization analysis. METHODOLOGY/PRINCIPAL FINDINGS: We genotyped 3 tag single nucleotide polymorphisms (SNPs [+1444T>C (rs1130864; +2303G>A (rs1205 and +4899T>G (rs 3093077] in the CRP gene and assessed CRP and carotid intima-media thickness (CIMT, a structural marker of atherosclerosis, in 4941 men and women aged 50-74 (mean 61 years (the Whitehall II Study. The 4 major haplotypes from the SNPs were consistently associated with CRP level, but not with other risk factors that might confound the association between CRP and CIMT. CRP, assessed both at mean age 49 and at mean age 61, was associated both with CIMT in age and sex adjusted standard regression analyses and with potential confounding factors. However, the association of CRP with CIMT attenuated to the null with adjustment for confounding factors in both prospective and cross-sectional analyses. When examined using genetic variants as the instrument for serum CRP, there was no inferred association between CRP and CIMT. CONCLUSIONS/SIGNIFICANCE: Both multivariable standard regression analysis and Mendelian randomization analysis suggest that the association of CRP with carotid atheroma indexed by CIMT may not be causal.

Oral microbiota in patients with atherosclerosis.

Science.gov (United States)

Fåk, Frida; Tremaroli, Valentina; Bergström, Göran; Bäckhed, Fredrik

2015-12-01

Recent evidence suggests that the microbiota may be considered as an environmental factor that contributes to the development of atherosclerosis. Periodontal disease has been associated with cardio- and cerebrovascular events, and inflammation in the periodontium is suggested to increase the systemic inflammatory level of the host, which may in turn influence plaque composition and rupture. We previously showed that bacteria from the oral cavity and the gut could be found in atherosclerotic plaques. To elucidate whether the oral microbiota composition differed between patients with asymptomatic and symptomatic atherosclerosis we performed pyrosequencing of the oral microbiota of 92 individuals including patients with asymptomatic and symptomatic atherosclerosis and control individuals without carotid plaques or previous stroke or myocardial infarction. The overall microbial structure was similar in controls and atherosclerosis patients, but patients with symptomatic atherosclerosis had higher relative abundance of Anaeroglobus (mean 0.040% (SD 0.049)) than the control group (0.010% (SD 0.028)) (P = 0.03). Using linear regression analysis, we found that Parvimonas associated positively with uCRP and Capnocytophaga, Catonella and Lactobacillus associated with blood lipid markers. In conclusion, abundance of Anaeroglobus in the oral cavity could be associated with symptomatic atherosclerosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A liquidity study on the Nasdaq OMX Stockholm exchange

OpenAIRE

Leffler, Fredrik; Dworsky Nylander, Adam

2012-01-01

As the demand for liquidity risk management has increased, the importance of comprehensive liquidity assessments of exchanges has been highlighted. This thesis investigates the liquidity on the Nasdaq OMX Stockholm exchange by using daily end of day data. The transaction cost is evaluated using the Holden model and the price impact from trading is evaluated using the Illiq model. Considering the three segments; small cap, mid cap, and large cap, the results suggest that both the transaction c...

[Transdisciplinary Approach for Sarcopenia. Sarcopenia and atherosclerosis].

Science.gov (United States)

Kohara, Katsuhiko

2014-10-01

Risk factors for sarcopenia, including aging, inflammation, oxidative stress, and sedentary life style, are also known as risks for atherosclerosis. Sarcopenia and atherosclerosis relate each other. We found that sarcopenia, especially sarcopenic visceral obesity in male subjects, was associated with higher arterial stiffness and central blood pressure. We also observed that leptin resistance may underlie the link between sarcopenia, sarcopenic obesity and atherosclerosis. In epidemiological studies, it has been demonstrated sarcopenic indices were associated with cardiovascular death. These findings indicate that sarcopenia could be regarded as risk factor for atherosclerosis and cardiovascular events.

Food redistribution in Stockholm : A comparative analysis of two scenarios – with and without a food bank

OpenAIRE

Persson, Anna

2016-01-01

Food waste is a serious problem in today’s society. Functional food waste is going to waste treatment while people are suffering from food insecurity. Food redistribution in form of a central food bank which collects food waste at food companies and delivers it to social organizations is a measure to deal with this issue. Stockholm City Mission plans to start up a central food bank in Stockholm and it is this implementation that is of focus in this report. The purpose of this study is to comp...

School Performance, School Segregation, and Stress-Related Symptoms: Comparing Helsinki and Stockholm

Science.gov (United States)

Modin, Bitte; Karvonen, Sakari; Rahkonen, Ossi; Östberg, Viveca

2015-01-01

This study investigates cross-cultural differences in the interrelation between school performance, school segregation, and stress-related health among 9th-grade students in the greater Stockholm and Helsinki areas. Contrary to the Swedish case, it has been proposed that school performance in Finland is largely independent of the specific school…

Association of Angiotensin-Converting Enzyme Genotype, Insertion/Deletion Polymorphism and Saphenous Vein Graft Atherosclerosis in Iranian Patients

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Neda Zeinali

2015-10-01

Full Text Available ABSTRACT OBJECTIVE: The aim of this study was to evaluate possible interactions among Angiotensin-I converting enzyme genotype, insertion/deletion polymorphism and atherosclerosis of vein grafts in Iranian patients, and characterize their clinical and demographic profile. METHODS: In this cross-sectional study, patients who underwent coronary artery bypass graft surgery more than five years ago, were included for angiographic analysis. Atherosclerosis was determined by quantitative angiography and adjusted Gensini score. The gene angiotensin converting enzyme I/D polymorphism was detected by polymerase chain reaction. RESULTS: A total of 102 patients participated in this study. Eighty-four patients were male. The frequency distribution of DD, ID and II polymorphism were 23.6%, 62.7% and 13.7% respectively. There were no differences among genotypic groups in age, sex, number of risk factors, number of vein grafts and months since bypass surgery. According to adjusted Gensini score [0.18±0.12 (II vs. 0.11±0.09 (ID and 0.1±0.09 (DD P=0.021] the II genotype was associated with severity of vein graft atherosclerosis. CONCLUSION: Although there are conflicting results about gene angiotensin converting enzyme I/D polymorphism and the degree of venous bypass graft degeneration, this study suggests an association between ACE genotype II and atherosclerosis of saphenous vein grafts, however, large samples considering clinical, demographic and ethnic profile are necessary to confirm these results.

Connective tissue diseases and noninvasive evaluation of atherosclerosis

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Ardita G

2014-06-01

Full Text Available Giorgio Ardita, Giacomo Failla, Paolo Maria Finocchiaro, Francesco Mugno, Luigi Attanasio, Salvatore Timineri, Michelangelo Maria Di SalvoCardiovascular Department, Angiology Unit, Ferrarotto Hospital, Catania, ItalyAbstract: Connective tissue diseases (CTDs are associated with increased risk of cardiovascular disease due to accelerated atherosclerosis. In patients with autoimmune disorders, in addition to traditional risk factors, an immune-mediated inflammatory process of the vasculature seems to contribute to atherogenesis. Several pathogenetic mechanisms have been proposed, including chronic inflammation and immunologic abnormalities, both able to produce vascular damage. Macrovascular atherosclerosis can be noninvasively evaluated by ultrasound measurement of carotid or femoral plaque. Subclinical atherosclerosis can be evaluated by well-established noninvasive techniques which rely on ultrasound detection of carotid intima-media thickness. Flow-mediated vasodilatation and arterial stiffness are considered markers of endothelial dysfunction and subclinical atherosclerosis, respectively, and have been recently found to be impaired early in a wide spectrum of autoimmune diseases. Carotid intima-media thickness turns out to be a leading marker of subclinical atherosclerosis, and many studies recognize its role as a predictor of future vascular events, both in non-CTD individuals and in CTD patients. In rheumatic diseases, flow-mediated dilatation and arterial stiffness prove to be strongly correlated with inflammation, disease damage index, and with subclinical atherosclerosis, although their prognostic role has not yet been conclusively shown. Systemic lupus erythematosus, rheumatoid arthritis, and likely antiphospholipid syndrome are better associated with premature and accelerated atherosclerosis. Inconclusive results were reported in systemic sclerosis.Keywords: rheumatic disease, subclinical atherosclerosis, arterial stiffness

Nuclear medicine and atherosclerosis

International Nuclear Information System (INIS)

Sinzinger, H.; Virgolini, I.

1990-01-01

Although the pathomechanisms of atherosclerosis are well known, their radioisotopic monitoring is still in its early childhood. The current radioisotope techniques are of only limited value for contributing to the clinical diagnosis of atherosclerosis. The limited reaction time of cellular blood constituents (platelets, monocytes) with the vascular surface at the injury site makes it very difficult to catch the point of injury. Lipoproteins excellently allow receptor imaging, while vascular monitoring is only of scientific interest at present. Labelling and subsequent imaging of components of the coagulation cascade have not succeeded so far, nor have attempts using unspecific labels such as porphyrin, polyclonal IgG and Fc fragments, for example. Preliminary evidence indicates that radioisotopic techniques may be of great benefit in the future in elucidating functional aspects of the disease, while they do not contribute to examining the stage and extent of atherosclerosis. (orig.)

Bullying in Context: An Analysis of Psychosomatic Complaints among Adolescents in Stockholm

Science.gov (United States)

Modin, Bitte; Låftman, Sara Brolin; Östberg, Viveca

2015-01-01

Using multilevel modeling, this study examined how different types of bullying, involving both peers and teachers, relate to psychosomatic health complaints. Data were obtained via the Stockholm School Survey from 41,032 ninth- and eleventh-grade students in the years 2004, 2006, 2008, and 2010. Results showed that students involved in bullying as…

Cytokines in atherosclerosis: an intricate balance

NARCIS (Netherlands)

Boshuizen, M.C.S.

2016-01-01

Atherosclerosis is the underlying pathology in the majority of clinical manifestations of cardiovascular diseases, which are nowadays the main global cause of mortality. Atherosclerosis is a lipid-driven chronic inflammatory disease of the arterial wall. This inflammatory response, with cytokines as

In-Vivo Assessment of Coronary Atherosclerosis

NARCIS (Netherlands)

G.A. Rodriguez-Granillo

2006-01-01

textabstractIntravascular ultrasound (IVUS) has emerged as a highly accurate tool for the serial assessment of the natural history of coronary atherosclerosis and to evaluate the effect of different conventional and emerging drug therapies on the progression of atherosclerosis. The

Probiotics and atherosclerosis – a new challenge?

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Chan Yee Kwan

2012-06-01

Full Text Available Background Atherosclerosis is the major cause of cardiovascular disease and stroke, which are among the top 10 leading causes of death worldwide. Pathogen-associated molecular patterns (PAMPs can activate toll-like receptors (TLRs and activate nuclear factor kappa B (NFκB signaling, a central pathway in inflammation, which regulates genes that encode proinflammatory molecules essential in atherogenesis. Lipopolysaccharides (LPS, which is unique to gram negative bacteria, as well as peptidoglycan (PGN, which is found in gram positive bacteria are PAMPS and ligands of TLR4 and TLR2, respectively, both of which are essential in plaque progression in atherosclerosis. Gastrointestinal tract is suggested to be the major site for absorption and translocation of TLR2 and TLR4 stimulants. Inflammation can result in a ‘leaky gut’ that leads to higher bacterial translocation, eventually the accumulation of LPS and PGN would activate TLRs and trigger inflammation through NFκB and promote further systemic complication like atherosclerosis. Probiotics, can protect the intestinal barrier to reduce bacterial translocation and have potential systemic anti-inflammatory properties.To evaluate whether probiotics can help reduce atherosclerotic development using in vivo study.Apolipoprotein E knockout (ApoE−/ −  mice were fed on high fat diet alone, with telmisartan (Tel (1 or 5 mg/kg/day, positive controls or with probiotics (VSL#3/LGG with or without Tel (1 mg/kg/day for 12 weeks.Probiotics, Tel, or a combination of both reduced lesion size at the aortic root significantly; VSL#3 reduced serum inflammatory adhesion molecules soluble E- (sE-selectin, soluble intercellular adhesion molecule 1 (sICAM-1, soluble vascular cell adhesion molecule 1 (sVCAM-1, and plaque disrupting factor matrix metalloproteinase (MMP-9 significantly; probiotics and Tel at 5 mg/kg/day could induce changes in gut microbiota population; the efficiency of lesion reduction seemed

MicroRNAs and atherosclerosis: new actors for an old movie.

Science.gov (United States)

Santovito, D; Mezzetti, A; Cipollone, F

2012-11-01

To date, cardiovascular diseases (CVDs) are the leading causes of morbidity and mortality worldwide. MicroRNAs (miRNAs) are endogenous, short, non-coding RNA sequences able to regulate gene expression principally at the post-transcriptional level. Initially, they were thought to be involved only in developmental timing of worms. Their involvement in human biology was recently discovered and many studies have been performed to demonstrate the role of miRNA in human cancer. Since the first observation in 2005 of their implication in cardiac biology, many studies have demonstrated their role in the genetic modulation of cardiovascular development and in cardiovascular diseases such as cardial remodeling and heart failure, cardiac arrhythmias, cardiac ischaemia, cardiac fibrosis, atherosclerosis and stroke. Thus, the aim of this review is to describe the role of miRNA in atherosclerosis development and evolution and to individuate their role as potential therapeutic target. Copyright © 2012 Elsevier B.V. All rights reserved.

Atherosclerosis VII

International Nuclear Information System (INIS)

Fidge, N.H.; Nestel, P.J.; Flinders Univ., Adelaide

1986-01-01

In these proceedings the major themes of the conference have been preserved and comprise epidemiology, lipoproteins, pathogenesis, and clinical, therapeutic and nutritional aspects. The diet-lipidcoronary artery disease hypothesis has been strengthened significantly. Several long-awaited trials, reviewed here, have provided very strong support for the rationale for treating hyperlipidemia. A strategy for the prevention of atherosclerosis was defined at the conference. The genesis of atherosclerosis was shown to be more firmly grounded in the influx of lipoprotein into the arterial wall. The regulation of these processes and the rapid advances made possible by new technology were detailed in several sessions. Important new developments in the clinical area and in pharmacology give promise of greatly improved management of established disease. However, the possibility of mounting large-scale preventive measures in the near future, was given credence in the epidemiology and nutrition workshops. (Auth.)

Effect of air pollution on the epiphytic flora of conifers in the Stockholm region

Energy Technology Data Exchange (ETDEWEB)

Lundstroem, H

1968-01-01

Epiphytic flora (especially lichens) have been investigated in order to see how they respond to air pollution. The study was restricted to those occurring up to a height of 2.3 m from the ground, on trunks of the conifers Picea abies and Pinus silvestries. The area of investigation lies north of Stockholm. Wind diagrams show a slight predominance of winds from Stockholm. This means that polluted air is spread out over the area of investigation. All epiphytic vegetation on the station-trees for which the species were determined are listed. The distribution of lichen species is discussed, especially how air pollution has affected the distributions of the three lichens, Hypogymnia physodes (L.) Zopf (syn. Parmelia physodes (L.) Ach.) Parmeliopsis ambigua (Wulf) Nyl. Pseudevernia furfuraceae (L.) Zopf (syn. Parmelia furfuraceae (L.) Ach.). Maps of distributions have been made for the most common epiphytes.

Framing the role of Decision Support in the case of Stockholm Congestion Charging Trial

DEFF Research Database (Denmark)

Gudmundsson, Henrik; Ericsson, Eva; Hugosson, Muriel Besser

2009-01-01

the way for investigating the use and role of ‘Decision Support’ in the Stockholm Congestion Charging experiment. We adopt a definition of Decision Support as the systematic application of externally produced knowledge in transport planning and policy making processes. We then derive an analytical...... framework from the research literature on ‘knowledge utilization’ in policy making. This research has generally found that both ‘technical’, ‘communicative’, and ‘institutional’ aspects of the Decision Support matter for its influence on actual policy making processes and results. In our analysis we find...... in a Swedish context, and the introduction of the Stockholm system has been highly controversial. Considerable efforts have therefore been undertaken to provide information that could serve as ‘Decision Support’ along the way. This has included e.g. modelling and forecasts before the Trial, a comprehensive...

Incentives for environmentally friendly vehicles. A report from the Environment and Health Protection Administration in Stockholm

Energy Technology Data Exchange (ETDEWEB)

Henriksson, Cecilia; Paedam, S. [Inregia AB, Stockholm (Sweden)

1999-11-01

This report deals with incentives for environmentally friendly vehicles. The report includes a description of the current status of these vehicles in Sweden, Stockholm County Council, and the City of Stockholm. A forecast of possible development of zero and low emission vehicles is carried out. The major obstacles which currently hinder a market for these vehicles are noted. In order to determine market readiness and factors which affect these firms' purchase of vehicles, interviews were carried out with private firms. This analysis indicates that institutional barriers in Sweden hinder zero and low emission vehicles, with laws and tax policies which offer conflicting signals. To follow international developments, these obstacles must be reduced. Therefore, it is important that Stockholm works to create a positive climate for environmentally friendly vehicles. This means that it is important that the policies recommended in this report are implemented with adequate intensity. Because knowledge about zero and low emission vehicles is limited, there is a need to produce factual information. Information can be spread to a larger group, but it is more cost effective to reach a group which is most likely to accept environmentally friendly vehicles. This could include companies with environmental profiles, or those who drive and use company cars. To increase the effectiveness of this information campaign, we suggest that the City also maintain a demonstration fleet with loaner cars for companies who wish to test these vehicles in daily operation before deciding whether or not to purchase them. The incentive package recommended for Stockholm includes offering parking rebates to various groups who park in the city centre; residents , commercial vehicles, and temporary visitors. For equity reasons, all groups should in practice be offered the rebate. To increase the positive effect of the incentive, environmentally friendly vehicles should also be allowed to drive in

Data on genetic associations of carotid atherosclerosis markers in Mexican American and European American rheumatoid arthritis subjects

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Rector Arya

2018-04-01

Full Text Available Carotid Intima-media thickness (CIMT and plaque are well established markers of subclinical atherosclerosis and are widely used for identifying subclinical atherosclerotic disease. We performed association analyses using Metabochip array to identify genetic variants that influence variation in CIMT and plaque, measured using B-mode ultrasonography, in rheumatoid arthritis (RA patients. Data on genetic associations of common variants associated with both CIMT and plaque in RA subjects involving Mexican Americans (MA and European Americans (EA populations are presented in this article. Strong associations were observed after adjusting for covariate effects including baseline clinical characteristics and statin use. Susceptibility loci and genes and/or nearest genes associated with CIMT in MAs and EAs with RA are presented. In addition, common susceptibility loci influencing CIMT and plaque in both MAs and EAs have been presented. Polygenic Risk Score (PRS plots showing complementary evidence for the observed CIMT and plaque association signals are also shown in this article. For further interpretation and details, please see the research article titled “A Genetic Association Study of Carotid Intima-Media Thickness (CIMT and Plaque in Mexican Americans and European Americans with Rheumatoid Arthritis” which is being published in Atherosclerosis (Arya et al., 2018 [1].(Arya et al., in press Thus, common variants in several genes exhibited significant associations with CIMT and plaque in both MAs and EAs as presented in this article. These findings may help understand the genetic architecture of subclinical atherosclerosis in RA populations.

Function and Therapeutic Potential of Mesenchymal Stem Cells in Atherosclerosis

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Feifei Li

2017-05-01

Full Text Available Atherosclerosis is a complicated disorder and largely attributable to dyslipidaemia and chronic inflammation. Despite therapeutic advances over past decades, atherosclerosis remains the leading cause of mortality worldwide. Due to their capability of immunomodulation and tissue regeneration, mesenchymal stem cells (MSCs have evolved as an attractive therapeutic agent in various diseases including atherosclerosis. Accumulating evidences support the protective role of MSCs in all stages of atherosclerosis. In this review, we highlight the current understanding of MSCs including their characteristics such as molecular markers, tissue distribution, migratory property, immune-modulatory competence, etc. We also summarize MSC functions in animal models of atherosclerosis. MSC transplantation is able to modulate cytokine and chemokine secretion, reduce endothelial dysfunction, promote regulatory T cell function, decrease dyslipidemia, and stabilize vulnerable plaques during atherosclerosis development. In addition, MSCs may migrate to lesions where they develop into functional cells during atherosclerosis formation. Finally, the perspectives of MSCs in clinical atherosclerosis therapy are discussed.

Age-dependent interaction of apolipoprotein E gene with eastern birthplace in Finland affects severity of coronary atherosclerosis and risk of fatal myocardial infarction--Helsinki Sudden Death Study.

Science.gov (United States)

Tyynelä, Petri; Goebeler, Sirkka; Ilveskoski, Erkki; Mikkelsson, Jussi; Perola, Markus; Lehtimäki, Terho; Karhunen, Pekka J

2013-05-01

Mortality from coronary heart disease (CHD) has been constantly higher in eastern late settlement regions compared to western early settlements in Finland, unrelated to classical risk factors. In line with this, eastern birthplace was an age-dependent predictor of severe coronary atherosclerosis and pre-hospital sudden coronary death among male residents of Helsinki. We investigated a possible interaction of apolipoprotein E (APOE) gene with birthplace on the risk of myocardial infarction (MI) and coronary atherosclerosis. APOE genotypes were analyzed in the Helsinki Sudden Death Study series comprising out-of-hospital deaths among males aged 33-70 years (n = 577), who were born in high (east, n = 273) or low (west, n = 304) CHD mortality area. Eastern-born men ≤ 55 years carried 30% more often (P = 0.017) and older men 40% less often (P = 0.022) the APOE ϵ4 allele compared to western-born men (P = 0.003 for birthplace-by-age interaction). In multivariate analysis, the ϵ4 allele associated with the risk of out-of-hospital MI (odds ratio 2.58; 95% CI 1.20-5.55; P = 0.016) only in eastern-born men and with advanced atherosclerosis in both regions of origin, respectively. Birthplace-bound risk of CHD was age-dependently modified by APOE ϵ4 allele, suggesting genetic differences in CHD susceptibility between early and late settlement regions in Finland and providing one explanation for the eastern high mortality.

Correlation between Mitochondrial Reactive Oxygen and Severity of Atherosclerosis

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Gabriel G. Dorighello

2016-01-01

Full Text Available Atherosclerosis has been associated with mitochondria dysfunction and damage. Our group demonstrated previously that hypercholesterolemic mice present increased mitochondrial reactive oxygen (mtROS generation in several tissues and low NADPH/NADP+ ratio. Here, we investigated whether spontaneous atherosclerosis in these mice could be modulated by treatments that replenish or spare mitochondrial NADPH, named citrate supplementation, cholesterol synthesis inhibition, or both treatments simultaneously. Robust statistical analyses in pooled group data were performed in order to explain the variation of atherosclerosis lesion areas as related to the classic atherosclerosis risk factors such as plasma lipids, obesity, and oxidative stress, including liver mtROS. Using three distinct statistical tools (univariate correlation, adjusted correlation, and multiple regression with increasing levels of stringency, we identified a novel significant association and a model that reliably predicts the extent of atherosclerosis due to variations in mtROS. Thus, results show that atherosclerosis lesion area is positively and independently correlated with liver mtROS production rates. Based on these findings, we propose that modulation of mitochondrial redox state influences the atherosclerosis extent.

The environmental fate of polybrominated diphenyl ethers in the centre of Stockholm - Assessment using a multimedia fugacity model

Energy Technology Data Exchange (ETDEWEB)

Palm, Anna

2001-01-01

A local-scale assessment of the environmental fate of three congeners of polybrominated diphenyl ethers (PBDEs) has been performed for the centre of Stockholm. The partitioning properties and main transport processes of these congeners in Stockholm are identified using a site-specific multimedia fugacity model, called CeStoc, that was developed and parameterized for the area of interest. CeStoc was based on level III and IV fugacity models. Five compartments were included: air, water, soil, sediment and an organic film covering the impervious surfaces in the city. The model was satisfactory calibrated with the PAH fluoranthene, before it was run for the compounds of interest. Validation with environmental levels of PBDEs was made where possible, showing reasonable agreement with model results. According to the CeStoc results, the majority of the PBDEs emitted are transported out of the region through air advection, implying that Stockholm may act as a source for chemical release to other regions. The largest sink for PBDEs in Stockholm is soil, closely followed by sediment, the two compartments together accounting for about 98 % of the total amount remaining in the system. The degree of bromination does not seem to have a large impact on the environmental distribution in this area, but further research on e.g. physical-chemical properties is necessary before this can be finally concluded. Predicted concentrations of individual PBDE congeners in sediment and water lie in the same range as measured levels of individual PCB-congeners, indicating that PBDEs could have an environmental impact of about the same size as the PCBs.

MicroRNA-181b Controls Atherosclerosis and Aneurysms Through Regulation of TIMP-3 and Elastin.

Science.gov (United States)

Di Gregoli, Karina; Mohamad Anuar, Nur Najmi; Bianco, Rosaria; White, Stephen J; Newby, Andrew C; George, Sarah J; Johnson, Jason L

2017-01-06

Atherosclerosis and aneurysms are leading causes of mortality worldwide. MicroRNAs (miRs) are key determinants of gene and protein expression, and atypical miR expression has been associated with many cardiovascular diseases; although their contributory role to atherosclerotic plaque and abdominal aortic aneurysm stability are poorly understood. To investigate whether miR-181b regulates tissue inhibitor of metalloproteinase-3 expression and affects atherosclerosis and aneurysms. Here, we demonstrate that miR-181b was overexpressed in symptomatic human atherosclerotic plaques and abdominal aortic aneurysms and correlated with decreased expression of predicted miR-181b targets, tissue inhibitor of metalloproteinase-3, and elastin. Using the well-characterized mouse atherosclerosis models of Apoe - /- and Ldlr -/- , we observed that in vivo administration of locked nucleic acid anti-miR-181b retarded both the development and the progression of atherosclerotic plaques. Systemic delivery of anti-miR-181b in angiotensin II-infused Apoe -/- and Ldlr -/- mice attenuated aneurysm formation and progression within the ascending, thoracic, and abdominal aorta. Moreover, miR-181b inhibition greatly increased elastin and collagen expression, promoting a fibrotic response and subsequent stabilization of existing plaques and aneurysms. We determined that miR-181b negatively regulates macrophage tissue inhibitor of metalloproteinase-3 expression and vascular smooth muscle cell elastin production, both important factors in maintaining atherosclerotic plaque and aneurysm stability. Validation studies in Timp3 -/- mice confirmed that the beneficial effects afforded by miR-181b inhibition are largely tissue inhibitor of metalloproteinase-3 dependent, while also revealing an additional protective effect through elevating elastin synthesis. Our findings suggest that the management of miR-181b and its target genes provides therapeutic potential for limiting the progression of

Stent-assisted angioplasty for intracranial atherosclerosis

International Nuclear Information System (INIS)

Nakahara, Toshinori; Sakamoto, Shigeyuki; Hamasaki, Osamu; Sakoda, Katsuaki

2002-01-01

We report on two patients with intracranial atherosclerosis of the carotid artery or vertebral artery treated with stent-assisted angioplasty. Both patients have severe intracranial atherosclerosis (>70%) with refractory symptoms despite optimal medical treatment. In both patients, a coronary balloon-expandable stent was successfully placed using a protective balloon technique without procedural complications. The patients were asymptomatic and neurologically intact at a mean clinical follow-up of 13 months. Follow-up angiograms did not show restenosis 3 or 4 months after procedure, respectively. Stent-assisted angioplasty for intracranial atherosclerosis in the elective patient has proven effective, with an acceptable low rate of morbidity and mortality. (orig.)

Intranasal delivery of E-selectin reduces atherosclerosis in ApoE-/- mice.

Directory of Open Access Journals (Sweden)

Xinhui Li

Full Text Available Mucosal tolerance to E-selectin prevents stroke and protects against ischemic brain damage in experimental models of stroke studying healthy animals or spontaneously hypertensive stroke-prone rats. A reduction in inflammation and neural damage was associated with immunomodulatory or "tolerogenic" responses to E-selectin. The purpose of the current study on ApoE deficient mice is to assess the capacity of this stroke prevention innovation to influence atherosclerosis, a major underlying cause for ischemic strokes; human E-selectin is being translated as a potential clinical prevention strategy for secondary stroke. Female ApoE-/- mice received intranasal delivery of E-selectin prior to (pre-tolerization or simultaneously with initiation of a high-fat diet. After 7 weeks on the high-fat diet, lipid lesions in the aorta, serum triglycerides, and total cholesterol were assessed as markers of atherosclerosis development. We also assessed E-selectin-specific antibodies and cytokine responses, in addition to inflammatory responses that included macrophage infiltration of the aorta and altered gene expression profiles of aortic mRNA. Intranasal delivery of E-selectin prior to initiation of high-fat chow decreased atherosclerosis, serum total cholesterol, and expression of the leucocyte chemoattractant CCL21 that is typically upregulated in atherosclerotic lesions of ApoE-/- mice. This response was associated with the induction of E-selectin specific cells producing the immunomodulatory cytokine IL-10 and immunosuppressive antibody isotypes. Intranasal administration of E-selectin generates E-selectin specific immune responses that are immunosuppressive in nature and can ameliorate atherosclerosis, a major risk factor for ischemic stroke. These results provide additional preclinical support for the potential of induction of mucosal tolerance to E-selectin to prevent stroke.

The Progression and Early detection of Subclinical Atherosclerosis (PESA) study

DEFF Research Database (Denmark)

Fernández-Ortiz, Antonio; Jiménez-Borreguero, L Jesús; Peñalvo, José L

2013-01-01

The presence of subclinical atherosclerosis is a likely predictor of cardiovascular events; however, factors associated with the early stages and progression of atherosclerosis are poorly defined.......The presence of subclinical atherosclerosis is a likely predictor of cardiovascular events; however, factors associated with the early stages and progression of atherosclerosis are poorly defined....

(-)-anipamil retards atherosclerosis in Watanabe heritable hyperlipidemic rabbits

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Hansen, B F; Mortensen, A; Hansen, J F

1995-01-01

Calcium antagonists have been reported to limit atherosclerosis in cholesterol fed rabbits. The purpose of this study was to examine the effect of the calcium antagonist (-)-anipamil on the spontaneous development of atherosclerosis in homozygote WHHL rabbits. From the age of 7 weeks, three groups...... differences were found in serum lipids (i.e., VLDL, IDL, LDL, HDL) in the study period among the three groups. Plasma anipamil at the end of the study was 0.23 +/- 6, and 202 +/- 19 ng/ml, respectively, in the three treatment groups. The degree of atherosclerosis in the abdominal aorta was significantly lower...... (p atherosclerosis in the abdominal aorta in WHHL rabbits....

Vinpocetine attenuates lipid accumulation and atherosclerosis formation

International Nuclear Information System (INIS)

Cai, Yujun; Li, Jian-Dong; Yan, Chen

2013-01-01

Highlights: •Vinpocetine attenuates hyperlipidemia-induced atherosclerosis in a mouse model. •Vinpocetine antagonizes ox-LDL uptake and accumulation in macrophages. •Vinpocetine blocks the induction of ox-LDL receptor LOX-1 in vitro and in vivo. -- Abstract: Atherosclerosis, the major cause of myocardial infarction and stroke, is a chronic arterial disease characterized by lipid deposition and inflammation in the vessel wall. Cholesterol, in low-density lipoprotein (LDL), plays a critical role in the pathogenesis of atherosclerosis. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. Recent study indicated that vinpocetine is a potent anti-inflammatory agent. However, its role in the pathogenesis of atherosclerosis remains unexplored. In the present study, we show that vinpocetine significantly reduced atherosclerotic lesion formation in ApoE knockout mice fed with a high-fat diet. In cultured murine macrophage RAW264.7 cells, vinpocetine markedly attenuated oxidized LDL (ox-LDL) uptake and foam cell formation. Moreover, vinpocetine greatly blocked the induction of ox-LDL receptor 1 (LOX-1) in cultured macrophages as well as in the LOX-1 level in atherosclerotic lesions. Taken together, our data reveal a novel role of vinpocetine in reduction of pathogenesis of atherosclerosis, at least partially through suppressing LOX-1 signaling pathway. Given the excellent safety profile of vinpocetine, this study suggests vinpocetine may be a therapeutic candidate for treating atherosclerosis

Vinpocetine attenuates lipid accumulation and atherosclerosis formation

Energy Technology Data Exchange (ETDEWEB)

Cai, Yujun [Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642 (United States); Li, Jian-Dong [Center for Inflammation, Immunity and Infection, and Department of Biology, Georgia State University, Atlanta, GA 30303 (United States); Yan, Chen, E-mail: Chen_Yan@urmc.rochester.edu [Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642 (United States)

2013-05-10

Highlights: •Vinpocetine attenuates hyperlipidemia-induced atherosclerosis in a mouse model. •Vinpocetine antagonizes ox-LDL uptake and accumulation in macrophages. •Vinpocetine blocks the induction of ox-LDL receptor LOX-1 in vitro and in vivo. -- Abstract: Atherosclerosis, the major cause of myocardial infarction and stroke, is a chronic arterial disease characterized by lipid deposition and inflammation in the vessel wall. Cholesterol, in low-density lipoprotein (LDL), plays a critical role in the pathogenesis of atherosclerosis. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. Recent study indicated that vinpocetine is a potent anti-inflammatory agent. However, its role in the pathogenesis of atherosclerosis remains unexplored. In the present study, we show that vinpocetine significantly reduced atherosclerotic lesion formation in ApoE knockout mice fed with a high-fat diet. In cultured murine macrophage RAW264.7 cells, vinpocetine markedly attenuated oxidized LDL (ox-LDL) uptake and foam cell formation. Moreover, vinpocetine greatly blocked the induction of ox-LDL receptor 1 (LOX-1) in cultured macrophages as well as in the LOX-1 level in atherosclerotic lesions. Taken together, our data reveal a novel role of vinpocetine in reduction of pathogenesis of atherosclerosis, at least partially through suppressing LOX-1 signaling pathway. Given the excellent safety profile of vinpocetine, this study suggests vinpocetine may be a therapeutic candidate for treating atherosclerosis.

Disruption of mammalian target of rapamycin complex 1 in macrophages decreases chemokine gene expression and atherosclerosis

NARCIS (Netherlands)

Ai, Ding; Jiang, Hongfeng; Westerterp, Marit; Murphy, Andrew J.; Wang, Mi; Ganda, Anjali; Abramowicz, Sandra; Welch, Carrie; Almazan, Felicidad; Zhu, Yi; Miller, Yury I.; Tall, Alan R.

2014-01-01

The mammalian target of rapamycin complex 1 inhibitor, rapamycin, has been shown to decrease atherosclerosis, even while increasing plasma low-density lipoprotein levels. This suggests an antiatherogenic effect possibly mediated by the modulation of inflammatory responses in atherosclerotic plaques.

Osteoprotegerin as a marker of atherosclerosis

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Hosbond, Susanne Elisabeth; Poulsen, Tina Svenstrup; Diederichsen, Axel Cosmus Pyndt

2012-01-01

Abstract Objective: Osteoprotegerin (OPG) may be involved in development of atherosclerosis. To evaluate plasma concentrations of OPG in individuals with stable coronary artery disease (CAD), acute coronary syndrome (ACS), peripheral artery disease (PAD) and cerebrovascular disease (CBVD) a syste......Abstract Objective: Osteoprotegerin (OPG) may be involved in development of atherosclerosis. To evaluate plasma concentrations of OPG in individuals with stable coronary artery disease (CAD), acute coronary syndrome (ACS), peripheral artery disease (PAD) and cerebrovascular disease (CBVD...... with clearly defined cohorts qualified for this review. Results: In 11 studies OPG concentrations were elevated. Severity of atherosclerosis was significantly associated with higher OPG concentrations compared to healthy controls. No association between PAD and OPG concentrations was observed. Conclusion: OPG...

Links between cardiovascular disease and osteoporosis in postmenopausal women: serum lipids or atherosclerosis per se?

DEFF Research Database (Denmark)

Bagger, Y Z; Rasmussen, Henrik Berg; Alexandersen, P

2007-01-01

Epidemiological observations suggest links between osteoporosis and risk of acute cardiovascular events and vice versa. Whether the two clinical conditions are linked by common pathogenic factors or atherosclerosis per se remains incompletely understood. We investigated whether serum lipids...... and polymorphism in the ApoE gene modifying serum lipids could be a biological linkage....

Epigenetic impact of endocrine disrupting chemicals on lipid homeostasis and atherosclerosis: a pregnane X receptor-centric view.

Science.gov (United States)

Helsley, Robert N; Zhou, Changcheng

2017-10-01

Despite the major advances in developing diagnostic techniques and effective treatments, atherosclerotic cardiovascular disease (CVD) is still the leading cause of mortality and morbidity worldwide. While considerable progress has been achieved to identify gene variations and environmental factors that contribute to CVD, much less is known about the role of "gene-environment interactions" in predisposing individuals to CVD. Our chemical environment has significantly changed in the last few decades, and there are more than 100,000 synthetic chemicals in the market. Recent large-scale human population studies have associated exposure to certain chemicals including many endocrine disrupting chemicals (EDCs) with increased CVD risk, and animal studies have also confirmed that some EDCs can cause aberrant lipid homeostasis and increase atherosclerosis. However, the underlying mechanisms of how exposure to those EDCs influences CVD risk remain elusive. Numerous EDCs can activate the nuclear receptor pregnane X receptor (PXR) that functions as a xenobiotic sensor to regulate host xenobiotic metabolism. Recent studies have demonstrated the novel functions of PXR in lipid homeostasis and atherosclerosis. In addition to directly regulating transcription, PXR has been implicated in the epigenetic regulation of gene transcription. Exposure to many EDCs can also induce epigenetic modifications, but little is known about how the changes relate to the onset or progression of CVD. In this review, we will discuss recent research on PXR and EDCs in the context of CVD and propose that PXR may play a previously unrealized role in EDC-mediated epigenetic modifications that affect lipid homeostasis and atherosclerosis.

Polymorphisms in IL-10 and INF-γ genes are associated with early atherosclerosis in coronary but not in carotid arteries: A study of 122 autopsy cases of young adults

Directory of Open Access Journals (Sweden)

José Carlos P. Esperança

2015-06-01

Full Text Available Atherosclerosis is a complex disease, involving both genetic and environmental factors. However, the influence of genetic variations on its early development remains unclear. This study examined the association of 12 different polymorphisms with atherosclerosis severity in anterior descending coronary (DA, n = 103 and carotid arteries (CA, n = 66 of autopsied young adults (<30 years old. Histological sections (H-E were classified according to the American Heart Association. Polymorphisms in ACE, TNF-α (−308G/A and −238 G/A, IFN-γ (+874 A/T, MMP-9 (−1562 C/T, IL-10 (−1082 A/G and −819 C/T, NOS3 (894 G/T, ApoA1 (rs964184, ApoE (E2E3E4 isoforms, and TGF-β (codons 25 and 10 genes were genotyped by gel electrophoresis or automatic DNA sequencing. Firearm projectile or car accident was the main cause of death, and no information about classical risk factors was available. Histological analysis showed high prevalence of type III atherosclerotic lesions in both DA (69% and CA (39% arteries, while severe type IV and V lesions were observed in 14% (DA and 33% (CA. Allele frequencies and genotype distributions were determined. Among the polymorphisms studied, IFN-γ and IL-10 (−1082 A/G were related to atherosclerosis severity in DA artery. No association between genotypes and lesion severity was found in CA. In conclusion, we observed that the high prevalence of early atherosclerosis in young adults is associated with IFN-γ (p < 0.001 and IL-10 (p = 0.013 genotypes. This association is blood vessel dependent. Our findings suggest that the vascular system presents site specialization, and specific genetic variations may provide future biomarkers for early disease identification.

[The receptor theory of atherosclerosis].

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Likhoded, V G; Bondarenko, V M; Gintsburg, A L

2010-01-01

Lipopolysaccharides of Gram-negative bacteria can interact with Toll-like receptor 4 (TLR4) and induce atheroma formation. The risk of atherosclerosis is decreased in case of TLR4 mutation. Other bacterial ligands and endogenous ligands of TLRs can also be involved in induction of atherogenesis. The general concept of atherosclerosis pathogentsis is presented. According to this concept atherogenesis can be initiated by some reactions resulting from interaction of exogenous and endogenous microbial ligands with Toll-like receptors.

Perinatal Hypercholesterolemia Exacerbates Atherosclerosis Lesions in Offspring by Altering Metabolism of Trimethylamine-N-Oxide and Bile Acids.

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Trenteseaux, Charlotte; Gaston, Anh-Thu; Aguesse, Audrey; Poupeau, Guillaume; de Coppet, Pierre; Andriantsitohaina, Ramaroson; Laschet, Jamila; Amarger, Valérie; Krempf, Michel; Nobecourt-Dupuy, Estelle; Ouguerram, Khadija

2017-11-01

Experimental studies suggest that maternal hypercholesterolemia may be relevant for the early onset of cardiovascular disease in offspring. We investigated the effect of perinatal hypercholesterolemia on the atherosclerosis development in the offspring of apolipoprotein E-deficient mice and the underlying mechanism. Atherosclerosis and related parameters were studied in adult male or female apolipoprotein E-deficient mice offspring from either normocholesterolemic or hypercholesterolemic mothers and normocholesterolemic fathers. Female born to hypercholesterolemic mothers had more aortic root lesions than female born to normocholesterolemic mothers. Lesions in whole aorta did not differ between groups. Higher trimethylamine-N-oxide levels and Fmo3 hepatic gene expression were higher in female born to hypercholesterolemic mothers offspring compared with female born to normocholesterolemic mothers and male. Trimethylamine-N-oxide levels were correlated with the size of atherosclerotic root lesions. Levels of hepatic cholesterol and gallbladder bile acid were greater in male born to hypercholesterolemic mothers compared with male born to normocholesterolemic mothers. At 18 weeks of age, female born to hypercholesterolemic mothers showed lower hepatic Scarb1 and Cyp7a1 but higher Nr1h4 gene expression compared with female born to normocholesterolemic mothers. Male born to hypercholesterolemic mothers showed an increase in Scarb1 and Ldlr gene expression compared with male born to normocholesterolemic mothers. At 25 weeks of age, female born to hypercholesterolemic mothers had lower Cyp7a1 gene expression compared with female born to normocholesterolemic mothers. DNA methylation of Fmo3, Scarb1 , and Ldlr promoter regions was slightly modified and may explain the mRNA expression modulation. Our findings suggest that maternal hypercholesterolemia may exacerbate the development of atherosclerosis in female offspring by affecting metabolism of trimethylamine-N-oxide and

ATHEROSCLEROSIS DISEASE: A MULTI-FACTORIAL PATHOLOGY

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Marcieli da Luz Giroldo1; Arienne Serrano Alves1; Francielle Baptista1

2007-06-01

Full Text Available Atherosclerosis or arterial stiffening is a gradual disease that restricts the normal blood flow in different areas of body and maylead to secondary illnesses as myocardial infarction and cerebral stroke. Innumerable factors are related to the development ofatherosclerosis, among them are the dyslipidemia; genetic factors; arterial hypertension; diabetes mellitus; obesity; smoking;lack of exercise; pulmonary infection by Chlamydia and stress. Due to multi-factorial atherosclerosis characteristics,innumerable drugs, with differentiated mechanisms of action, are being elaborated to be used in prevention and control of thisdisease. However, beyond the pharmacological therapy, a balanced diet, physical activity and elimination of risk habits, assmoking, also are need for controlling atherosclerosis progression, as well as for the increase of expectative and quality of life

Role of gut microbiota in atherosclerosis

DEFF Research Database (Denmark)

Jonsson, Annika Lindskog; Bäckhed, Gert Fredrik

2017-01-01

describe three pathways by which microbiota might affect atherogenesis. First, local or distant infections might cause a harmful inflammatory response that aggravates plaque development or triggers plaque rupture. Second, metabolism of cholesterol and lipids by gut microbiota can affect the development...... of atherosclerotic plaques. Third, diet and specific components that are metabolized by gut microbiota can have various effects on atherosclerosis; for example, dietary fibre is beneficial, whereas the bacterial metabolite trimethylamine-N-oxide is considered harmful. Although specific bacterial taxa have been...... associated with atherosclerosis, which is supported by increasing mechanistic evidence, several questions remain to be answered to understand fully how the microbiota contributes to atherosclerosis and cardiovascular disease. Such knowledge might pave the way for novel diagnostics and therapeutics based...

Oral microbiota in patients with atherosclerosis

DEFF Research Database (Denmark)

Fåk, Frida; Tremaroli, Valentina; Bergström, Göran

2015-01-01

BACKGROUND AND AIMS: Recent evidence suggests that the microbiota may be considered as an environmental factor that contributes to the development of atherosclerosis. Periodontal disease has been associated with cardio- and cerebrovascular events, and inflammation in the periodontium is suggested...... to increase the systemic inflammatory level of the host, which may in turn influence plaque composition and rupture. We previously showed that bacteria from the oral cavity and the gut could be found in atherosclerotic plaques. METHODS: To elucidate whether the oral microbiota composition differed between...... patients with asymptomatic and symptomatic atherosclerosis we performed pyrosequencing of the oral microbiota of 92 individuals including patients with asymptomatic and symptomatic atherosclerosis and control individuals without carotid plaques or previous stroke or myocardial infarction. RESULTS...

Dental erosion, prevalence and risk factors among a group of adolescents in Stockholm County.

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Skalsky Jarkander, M; Grindefjord, M; Carlstedt, K

2018-02-01

To investigate the prevalence and risk factors of dental erosion (DE) among a group of adolescents in Stockholm County. This cross sectional cohort study was conducted at three clinics of the Public Dental Service in Stockholm County. Fifteen and 17 year old adolescents (1335) who scheduled their regular dental health examination were asked to participate. After drop-outs a sample of 1071 individuals, 547 males and 524 females were enrolled in the study. Presence of erosive wear was diagnosed (yes/no) on marker teeth by trained dentists/dental hygienists and photographs were taken. The adolescents answered a questionnaire regarding oral symptoms, dietary and behavioural factors. Two calibrated specialist dentists performed evaluation of the photographs for severity of DE using a modified version of the Simplified Erosion Partial Recording System (SEPRS). DE was clinically diagnosed in 28.3% of 15 years old and 34.3% of 17 years old. Severe erosive wear (grade 3 and 4 according to SEPRS) was found in 18.3% of the adolescents based upon the intra-oral photographs. DE was more prevalent and severe among males than females. Clinically diagnosed erosive lesions correlated significantly with soft drink consumption (p < 0.001), the use of juice or sport drinks as a thirst quencher after exercise (p = 0.006) and tooth hypersensitivity when eating and drinking (p = 0.012). Furthermore, self-assessed gastric reflux was a factor strongly associated with DE (p < 0.001). The study indicated that DE was common among adolescents in Stockholm County and associated with both internal and external risk factors.

Influence of Erythrocyte Membrane Stability in Atherosclerosis.

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da Silva Garrote-Filho, Mario; Bernardino-Neto, Morun; Penha-Silva, Nilson

2017-04-01

The purpose of this study is to show how an excess of cholesterol in the erythrocyte membrane contributes stochastically to the progression of atherosclerosis, leading to damage in blood rheology and O 2 transport, deposition of cholesterol (from trapped erythrocytes) in an area of intraplaque hemorrhage, and local exacerbation of oxidative stress. Cholesterol contained in the membrane of erythrocytes trapped in an intraplaque hemorrhage contributes to the growth of the necrotic nucleus. There is even a relationship between the amount of cholesterol in the erythrocyte membrane and the severity of atherosclerosis. In addition, the volume variability among erythrocytes, measured by RDW, is predictive of a worsening of this disease. Erythrocytes contribute to the development of atherosclerosis in several ways, especially when trapped in intraplate hemorrhage. These erythrocytes are oxidized and phagocytosed by macrophages. The cholesterol present in the membrane of these erythrocytes subsequently contributes to the growth of the atheroma plaque. In addition, when they rupture, erythrocytes release hemoglobin, which leads to the generation of free radicals. Finally, increased RDW may predict the worsening of atherosclerosis, due to the effects of inflammation and oxidative stress on erythropoiesis and erythrocyte volume. A better understanding of erythrocyte participation in atherosclerosis may contribute to the improvement of the prevention and treatment strategies of this disease.

Effects of Curcuma comosa on the expression of atherosclerosis-related cytokine genes in rabbits fed a high-cholesterol diet.

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Charoenwanthanang, Puttavee; Lawanprasert, Somsong; Phivthong-Ngam, Laddawal; Piyachaturawat, Pawinee; Sanvarinda, Yupin; Porntadavity, Sureerut

2011-04-12

Curcuma comosa has been known to have potential use in cardiovascular diseases, but its immunoregulatory role in atherosclerosis development and liver toxicity has not been well studied. We therefore investigated the effects of Curcuma comosa on the expression of atherosclerosis-related cytokine genes in rabbits fed a high-cholesterol diet. Twelve male New Zealand White rabbits were treated with 1.0% cholesterol for one month and were subsequently treated with 0.5% cholesterol either alone, or in combination with 5mg/kg/day of simvastatin or with 400mg/kg/day of Curcuma comosa powder for three months. The expression of IL-1, MCP-1, TNF-α, IL-10, and TGF-β in the isolated abdominal aorta and liver were determined by real-time RT-PCR. Liver toxicity was determined by hepatic enzyme activity. Curcuma comosa significantly decreased the expression of pro-inflammatory cytokines, leading to a stronger reduction in IL-1, MCP-1, and TNF-α expression compared to that was suppressed by simvastatin treatment. However, neither Curcuma comosa nor simvastatin affected the expression of anti-inflammation cytokines. In the liver, Curcuma comosa insignificantly decreased the expression of pro-inflammatory cytokines and significantly increased the expression of the anti-inflammatory cytokine IL-10 without altering the activity of hepatic enzymes. In contrast, simvastatin significantly increased the MCP-1 and TNF-α expressions and serum ALT level, without affecting the expression of anti-inflammatory cytokines. In this study, we demonstrated that Curcuma comosa exerts anti-inflammatory activity in the aorta and liver without causing liver toxicity, indicating that Curcuma comosa is a potential candidate as an alternative agent in cardiovascular disease therapy. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Monocyte gene expression in childhood obesity is associated with obesity and complexity of atherosclerosis in adults

NARCIS (Netherlands)

Keustermans, G C; Kofink, Daniel; Eikendal, A.L.; de Jager, W.; Meerding, J.; Nuboer, R.; Waltenberger, J.; Kraaijeveld, A.O.; Jukema, J Wouter; Sels, J.W.; Garssen, J; Prakken, Berent J.; Asselbergs, Folkert W; Kalkhoven, E.; Hoefer, Imo E.; Pasterkamp, G.; Schipper, Henk S

2017-01-01

Childhood obesity coincides with increased numbers of circulating classical CD14++CD16- and intermediate CD14++CD16+ monocytes. Monocytes are key players in the development and exacerbation of atherosclerosis, which prompts the question as to whether the monocytosis in childhood obesity contributes

Function of CD147 in atherosclerosis and atherothrombosis

Science.gov (United States)

Wang, Cuiping; Jin, Rong; Zhu, Xiaolei; Yan, Jinchuan; Guohong, Li

2015-01-01

CD147, a member of the immunoglobulin super family, is a well-known potent inducer of extracellular matrix metalloproteinases. Studies show that CD147 is upregulated in inflammatory diseases. Atherosclerosis is a chronic inflammatory disease of the artery wall. Further understanding of the functions of CD147 in atherosclerosis and atherothrombosis may provide a new strategy for preventing and treating cardiovascular disease. In this review, we discuss how CD147 contributes to atherosclerosis and atherothrombosis. PMID:25604960

Inflammation and immune system interactions in atherosclerosis

NARCIS (Netherlands)

Legein, Bart; Temmerman, Lieve; Biessen, Erik A. L.; Lutgens, Esther

2013-01-01

Cardiovascular disease (CVD) is the leading cause of mortality worldwide, accounting for 16.7 million deaths each year. The underlying cause of the majority of CVD is atherosclerosis. In the past, atherosclerosis was considered to be the result of passive lipid accumulation in the vessel wall.

RIP3-dependent necrosis induced inflammation exacerbates atherosclerosis

Energy Technology Data Exchange (ETDEWEB)

Meng, Lingjun, E-mail: menglingjun@nibs.ac.cn [College of Biological Sciences, China Agricultural University, Beijing 100094 (China); National Institute of Biological Sciences, Beijing 102206 (China); Jin, Wei [Institute for Immunology, Tsinghua University, Beijing 100084 (China); Wang, Yuhui [Institute of Cardiovascular Sciences, Health Science Center, Peking University, Beijing 100191 (China); Huang, Huanwei; Li, Jia; Zhang, Cai [National Institute of Biological Sciences, Beijing 102206 (China)

2016-04-29

Atherothrombotic vascular disease is already the leading cause of mortality worldwide. Atherosclerosis shares features with diseases caused by chronic inflammation. More attention should concentrates on the innate immunity effect atherosclerosis progress. RIP3 (receptor-interacting protein kinase 3) act through the transcription factor named Nr4a3 (Nuclear orphan receptors) to regulate cytokine production. Deletion RIP3 decreases IL-1α production. Injection of anti-IL-1α antibody protects against the progress of atherosclerosis in ApoE −/− mice. RIP3 as a molecular switch in necrosis, controls macrophage necrotic death caused inflammation. Inhibiting necrosis will certainly reduce atherosclerosis through limit inflammation. Necrotic cell death caused systemic inflammation exacerbated cardiovascular disease. Inhibition of necrosis may yield novel therapeutic targets for treatment in years to come. - Highlights: • RIP3 regulate the Nr4a3 to control cytokine production. • Deletion RIP3 decreases IL-1a production. • Injection anti-IL-1a antibody protects against the progress of atherosclerosis. • RIP3 controls macrophage necrotic dead caused inflammation.

RIP3-dependent necrosis induced inflammation exacerbates atherosclerosis

International Nuclear Information System (INIS)

Meng, Lingjun; Jin, Wei; Wang, Yuhui; Huang, Huanwei; Li, Jia; Zhang, Cai

2016-01-01

Atherothrombotic vascular disease is already the leading cause of mortality worldwide. Atherosclerosis shares features with diseases caused by chronic inflammation. More attention should concentrates on the innate immunity effect atherosclerosis progress. RIP3 (receptor-interacting protein kinase 3) act through the transcription factor named Nr4a3 (Nuclear orphan receptors) to regulate cytokine production. Deletion RIP3 decreases IL-1α production. Injection of anti-IL-1α antibody protects against the progress of atherosclerosis in ApoE −/− mice. RIP3 as a molecular switch in necrosis, controls macrophage necrotic death caused inflammation. Inhibiting necrosis will certainly reduce atherosclerosis through limit inflammation. Necrotic cell death caused systemic inflammation exacerbated cardiovascular disease. Inhibition of necrosis may yield novel therapeutic targets for treatment in years to come. - Highlights: • RIP3 regulate the Nr4a3 to control cytokine production. • Deletion RIP3 decreases IL-1a production. • Injection anti-IL-1a antibody protects against the progress of atherosclerosis. • RIP3 controls macrophage necrotic dead caused inflammation.

Stockholm conference. Summary of the international conference on the security of material in Stockholm, Sweden

International Nuclear Information System (INIS)

Hoskins, Richard

2001-01-01

Preventing illicit uses of nuclear material and radioactive sources was a major international concern even before the spectre of nuclear terrorism was raised by terrorist attacks in September 2001. At an IAEA international conference in Stockholm, Sweden, convened in May 2001, international experts examined ways and means of strengthening systems for the protection of nuclear and radioactive material. The Conference - formally called 'Security of Material: Measures to Prevent, Intercept and Respond to Illicit Uses of Nuclear Material and Radioactive Sources' - was attended by more than 300 experts from around the world. It was organized by the IAEA in cooperation with the European Police Office (Europol), the International Criminal Police Organization - Interpol (ICPO-Interpol), and the World Customs Organization (WCO), and hosted by the Swedish Nuclear Power Inspectorate. In the Conference Summary Document, participants underscored the importance of establishing stronger systems for nuclear security, and they outlined a number of steps for the future in particular areas. Following are excerpts from the Document. More information on the Conference is accessible on the IAEA's WorldAtom Web site at http://www.iaea.org/ worldatom/Press/P r elease/2001/ prn0110.shtml

HCH contamination from former pesticide production in Brazil--a challenge for the Stockholm Convention implementation.

Science.gov (United States)

Torres, J P M; Fróes-Asmus, C I R; Weber, R; Vijgen, J M H

2013-04-01

Hexachlorocyclohexane (HCH) isomers (α-, β- and γ- HCH [lindane]) were recently added to the list of persistent organic pollutants regulated by the Stockholm Convention, and therefore, the legacy of HCH and lindane production has become an issue of global relevance. The production of lindane with the much larger quantities of associated waste isomers has generated large waste deposits and contaminated sites. This article presents an overview of HCH-polluted sites in Brazil as a basis for further activities related to the Stockholm Convention. The locations of HCH stockpiles and contaminated sites in Brazil arising from production and formulation have been compiled and mapped. This shows that the measures taken over the past 25 years have not resulted in remediation of the HCH pollution. An exposure risk study has been summarised for one major site and is included to demonstrate the contemporary relevance of the contamination. Major site remediation efforts are planned at one site but people live close to several other sites, and there is an urgent need of further assessments and remediation to ensure the protection of human health and the environment. The Stockholm Convention requires a systematic approach and should be adopted for the assessment of all sites and appropriate isolation/remediation measures should be facilitated. The appropriate planning of these activities for the production site in Rio de Janeiro could be a positive contribution for Rio+20 highlighting that green economy and sustainable production also include the appropriate management of legacies of historic production of an industrial sector (here the organochlorine industry).

Gene expression patterns in peripheral blood correlate with the extent of coronary artery disease.

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Peter R Sinnaeve

Full Text Available Systemic and local inflammation plays a prominent role in the pathogenesis of atherosclerotic coronary artery disease, but the relationship of whole blood gene expression changes with coronary disease remains unclear. We have investigated whether gene expression patterns in peripheral blood correlate with the severity of coronary disease and whether these patterns correlate with the extent of atherosclerosis in the vascular wall. Patients were selected according to their coronary artery disease index (CADi, a validated angiographical measure of the extent of coronary atherosclerosis that correlates with outcome. RNA was extracted from blood of 120 patients with at least a stenosis greater than 50% (CADi > or = 23 and from 121 controls without evidence of coronary stenosis (CADi = 0. 160 individual genes were found to correlate with CADi (rho > 0.2, P<0.003. Prominent differential expression was observed especially in genes involved in cell growth, apoptosis and inflammation. Using these 160 genes, a partial least squares multivariate regression model resulted in a highly predictive model (r(2 = 0.776, P<0.0001. The expression pattern of these 160 genes in aortic tissue also predicted the severity of atherosclerosis in human aortas, showing that peripheral blood gene expression associated with coronary atherosclerosis mirrors gene expression changes in atherosclerotic arteries. In conclusion, the simultaneous expression pattern of 160 genes in whole blood correlates with the severity of coronary artery disease and mirrors expression changes in the atherosclerotic vascular wall.

Regulation of T cell responses in atherosclerosis

NARCIS (Netherlands)

Puijvelde, Gijsbrecht Henricus Maria van

2007-01-01

One of the most important characteristics of atherosclerosis is the chronic inflammatory response in which T cells and NKT cells are very important. In this thesis several methods to modulate the activity of these T and NKT cells in atherosclerosis are described. The induction of regulatory T cells

Carotid Atherosclerosis and Cognitive Impairment in Nonstroke Patients

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Wei-Hong Chen

2017-01-01

Conclusions: Carotid atherosclerosis can be used to predict the risk of cognitive impairment. Furthermore, diagnosing and treating carotid atherosclerosis at early stage might help clinicians prevent and treat vascular cognitive impairment in nonstroke patients.

A lipoprotein lipase mutation (Asn291Ser) is associated with reduced HDL cholesterol levels in premature atherosclerosis

NARCIS (Netherlands)

Reymer, P.W.A.; Gagné, S E; Groenemeyer, B E; Zhang, H; Forsyth, I; Jansen, H; Seidell, J C; Kromhout, D.; Lie, K E; Kastelein, J.J.

1995-01-01

A reduction of high density lipoprotein cholesterol (HDC) is recognized as an important risk factor for coronary artery disease (CAD). We now show in approximately 1 in 20 males with proven atherosclerosis that an Asn291Ser mutation in the human lipoprotein lipase (LPL) gene is associated with

Stockholm Safety Conference. Analysis of the sessions on radiological protection, licensing and risk assessment

International Nuclear Information System (INIS)

Gea, A.

1981-01-01

A summary of the sessions on radiological protection, licensing and risk assessment in the safety conference of Stockholm is presented. It is considered the new point of view of the nuclear safety, probabilistic analysis, components failures probability and accident analysis. They are included conclusions applicable in many cases to development countries. (author)

Life stress and atherosclerosis: a pathway through unhealthy lifestyle.

Science.gov (United States)

Mainous, Arch G; Everett, Charles J; Diaz, Vanessa A; Player, Marty S; Gebregziabher, Mulugeta; Smith, Daniel W

2010-01-01

To examine the relationship between a general measure of chronic life stress and atherosclerosis among middle aged adults without clinical cardiovascular disease via pathways through unhealthy lifestyle characteristics. We conducted an analysis of The Multi-Ethnic Study of Atherosclerosis (MESA). The MESA collected in 2000 includes 5,773 participants, aged 45-84. We computed standard regression techniques to examine the relationship between life stress and atherosclerosis as well as path analysis with hypothesized paths from stress to atherosclerosis through unhealthy lifestyle. Our outcome was sub-clinical atherosclerosis measured as presence of coronary artery calcification (CAC). A logistic regression adjusted for potential confounding variables along with the unhealthy lifestyle characteristics of smoking, excessive alcohol use, high caloric intake, sedentary lifestyle, and obesity yielded no significant relationship between chronic life stress (OR 0.93, 95% CI 0.80-1.08) and CAC. However, significant indirect pathways between chronic life stress and CAC through smoking (p = .007), and sedentary lifestyle (p = .03) and caloric intake (.002) through obesity were found. These results suggest that life stress is related to atherosclerosis once paths of unhealthy coping behaviors are considered.

The anti-inflammatory effect of kaempferol on early atherosclerosis in high cholesterol fed rabbits

Science.gov (United States)

2013-01-01

Background Atherosclerosis has been widely accepted as an inflammatory disease of vascular, adhesion molecules play an important role in the early progression of it. The aim of the present study was to evaluate the effect of kaempferol on the inflammatory molecules such as E-selectin (E-sel), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesionmolecule-1 (VCAM-1) and monocyte chemotactic protein-1 (MCP-1) in high cholesterol induced atherosclerosis rabbit models. Methods Thirty male New Zealand white (NZW) rabbits were randomly divided into five groups, control group, model group, fenofibrate (12mg/kg) group and kaempferol groups (150 mg/kg and 30 mg/kg). The rabbits were fed with a normal diet or a high cholesterol diet for 10 weeks. Levels of blood lipids, serum tumour-necrosis factor-alpha (TNF-α) and serum interleukin-1beta (IL-1β) were detected at the end of the sixth and tenth week. Malonaldehyde (MDA) level and superoxide dismutase (SOD) activity in serum were also determined. Lesion areas of the aorta were measured with morphometry analysis after ten weeks. Gene expression of E-sel, ICAM-1, VCAM-1 and MCP-1 in aortas was determined by RT-PCR (reverse transcription-polymerase chain reaction). Immunohistochemical staining was employed to measure protein expression of E-sel, ICAM-1, VCAM-1 and MCP-1. Results Model rabbits fed with ten weeks of high-cholesterol diet developed significant progression of atherosclerosis. Compared with the control, levels of blood lipids, TNF-α, IL-1β and MDA increased markedly in serum of model rabbits, while SOD levels decreased. Gene and protein expressions of E-sel, ICAM-1, VCAM-1 and MCP-1 in atherosclerotic aortas increased remarkably in model group. However, comparing to the model rabbits, levels of TNF-α, IL-1β and MDA decreased significantly and serum SOD activity increased, gene and protein expressions of E-sel, ICAM-1, VCAM-1 and MCP-1 in aortas decreased significantly with the treatment of

The Stockholm-3 (STHLM3) Model can Improve Prostate Cancer Diagnostics in Men Aged 50-69 yr Compared with Current Prostate Cancer Testing.

Science.gov (United States)

Eklund, Martin; Nordström, Tobias; Aly, Markus; Adolfsson, Jan; Wiklund, Peter; Brandberg, Yvonne; Thompson, James; Wiklund, Fredrik; Lindberg, Johan; Presti, Joseph C; StLezin, Mark; Clements, Mark; Egevad, Lars; Grönberg, Henrik

2016-11-23

Prostate cancer screening is associated with low specificity, unnecessary biopsies, and overdiagnosis. We have previously shown that the Stockholm-3 model (S3M) can reduce biopsies compared with using prostate-specific antigen (PSA) ≥3ng/ml as an indication for biopsy. Urologists in today's current prostate cancer testing (CPT) have access to numerous variables in addition to PSA (eg, age, ethnicity, family history, free PSA, PSA velocity, digital rectal examination, and prostate volume) to support biopsy decisions. We estimated the number of prostate cancers diagnosed and prostate biopsies performed if S3M replaced CPT in Stockholm, Sweden, by comparing biopsy results in 56 282 men who underwent PSA testing according to CPT in Stockholm in 2011 with the 47 688 men enrolled in the STHLM3 validation cohort 2012-2015. With the same sensitivity as CPT to diagnose Gleason score ≥7 prostate cancer, S3M was estimated to reduce the number of men biopsied by 53% (95% confidence interval [CI]: 41-65%), avoid 76% (95% CI: 67-81%) of negative biopsies, and reduce Gleason score 6 cancers by 23% (95% CI: 6-40%). S3M has the potential to improve prostate cancer diagnostics by better selecting men with high risk of GS ≥7 prostate cancer. We modeled the effect the Stockholm-3 model would have on prostate cancer diagnostics if it replaced current clinical practice. We found that Stockholm-3 model may substantially reduce the number of biopsies, while maintaining the same sensitivity to diagnose clinically significant prostate cancer. Copyright © 2016. Published by Elsevier B.V.

Concept of Atherosclerosis Velocity: Is It a Better Measure of Cardiovascular Risk?

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Seyyed Mohammad Reza Kazemi-Bajestani

2013-09-01

Full Text Available In most cases atherosclerosis is the underlying cause of vascular diseases, including heart disease and stroke. It is believed that endothelial injury is the earliest change in the artery wall and that this precedes the formation of lesions of atherosclerosis. Recent developments in the field of atherosclerosis have led to a renewed interest in the recognition of the parameter of time in the atherosclerosis process. We believe that the factors determining the time-dependent rate of atherosclerosis progression are important, and it is in this context that we wish to propose for the first time the term “atherosclerosis velocity”. In this review article, we summarize the existing evidence regarding atherosclerosis velocity and discuss the importance of this issue.

Atherosclerosis profile and incidence of cardiovascular events: a population-based survey

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Bullano Michael F

2009-09-01

Full Text Available Abstract Background Atherosclerosis is a chronic progressive disease often presenting as clinical cardiovascular disease (CVD events. This study evaluated the characteristics of individuals with a diagnosis of atherosclerosis and estimated the incidence of CVD events to assist in the early identification of high-risk individuals. Methods Respondents to the US SHIELD baseline survey were followed for 2 years to observe incident self-reported CVD. Respondents had subclinical atherosclerosis if they reported a diagnosis of narrow or blocked arteries/carotid artery disease without a past clinical CVD event (heart attack, stroke or revascularization. Characteristics of those with atherosclerosis and incident CVD were compared with those who did not report atherosclerosis at baseline but had CVD in the following 2 years using chi-square tests. Logistic regression model identified characteristics associated with atherosclerosis and incident events. Results Of 17,640 respondents, 488 (2.8% reported having subclinical atherosclerosis at baseline. Subclinical atherosclerosis was associated with age, male gender, dyslipidemia, circulation problems, hypertension, past smoker, and a cholesterol test in past year (OR = 2.2 [all p Conclusion Self-report of subclinical atherosclerosis identified an extremely high-risk group with a >25% risk of a CVD event in the next 2 years. These characteristics may be useful for identifying individuals for more aggressive diagnostic and therapeutic efforts.

Atherosclerosis in Juvenile Idiopathic Arthritis

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Ewa Jednacz

2012-01-01

Full Text Available Atherosclerosis is a chronic inflammatory disease of the arteries. Clinical consequences of the atherosclerotic process occur in the adult population, however atherosclerotic process begins in childhood. The classic risk factors for atherosclerosis include obesity, dyslipidaemia, age, gender or family history. In recent years, attention has been drawn to the similarity between atherosclerotic inflammatory processes and inflammatory changes in the course of systemic connective tissue disease, in particular systemic lupus etythematosus (SLE or rheumatoid arthritis (RA. There is also observed the similarity of the pathogenetic background of development of atherosclerosis and juvenile idiopathic arthritis (JIA. Elevated levels of pro-inflammatory cytokines are observed in the course of juvenile idiopathic arthritis. Also homocysteine concentrations, which may play a significant role in the development of atherosclerotic lesions, are observed higher in patients with JIA. Some studies revealed higher carotid intima-media thickness (IMT index values in children with JIA. In view of the fact that atherosclerotic process begins as early as in childhood, the introduction of appropriate preventive measures in children is a matter of utmost importance.

Very low levels of HDL cholesterol and atherosclerosis, a variable relationship – a review of LCAT deficiency

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Savel J

2012-06-01

Full Text Available Julia Savel,1,2 Marianne Lafitte,1 Yann Pucheu,1,3 Vincent Pradeau,1 Antoine Tabarin,2,3 Thierry Couffinhal1,3,41Centre d'Exploration, de Prévention et de Traitement de l'Athérosclérose, Hôpital Cardiologique, 2Service d'endocrinologie, CHU Bordeaux, Université Bordeaux Segalen, Bordeaux, France; 3Université de Bordeaux Adaptation cardiovasculaire à l'ischémie, 4INSERM, Adaptation cardiovasculaire à l'ischémie, U1034, Pessac, FranceAbstract: A number of epidemiological and clinical studies have demonstrated that plasma high-density lipoprotein (HDL level is a strong inverse predictor of cardiovascular events. HDL is believed to retard the formation of atherosclerotic lesions by removing excess cholesterol from cells and preventing endothelial dysfunction. Lecithin cholesterol acyltransferase (LCAT plays a central role in the formation and maturation of HDL, and in the intravascular stage of reverse cholesterol transport: a major mechanism by which HDL modulates the development and progression of atherosclerosis. A defect in LCAT function would be expected to enhance atherosclerosis, by interfering with the reverse cholesterol transport step. As such, one would expect to find more atherosclerosis and cardiovascular events in LCAT-deficient patients. But this relationship is not always evident. In this review, we describe contradictory reports in the literature about cardiovascular risks in this patient population. We discuss the paradoxical finding of severe HDL deficiency and an absence of subclinical atherosclerosis in LCAT-deficient patients, which has been used to reject the hypothesis that HDL level is important in the protection against atherosclerosis. Furthermore, to illustrate this paradoxical finding, we present a case study of one patient, referred for evaluation of global cardiovascular risk in the presence of a low HDL cholesterol level, who was diagnosed with LCAT gene mutations.Keywords: atherosclerosis, LCAT function

Foreign Reports about Stepan Razin’s Execution. New Documents from the Stockholm Archive

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Gleb M. Kazakov

2017-12-01

Full Text Available This paper analyzes reports written by foreign authors about the execution of Stepan Razin. The main focus is on two dispatches written by the Swedish citizen and merchant in Moscow, Christoff Koch, in May–June 1671 and sent to Narva, and from there, they were forwarded to the Swedish capital, among other places. They are now kept at the State Archives in Stockholm, and they have not been discussed previously in the scholarly literature. The paper contains the full translation into Russian of two long reports written by Koch about Razin’s capture, delivery to Moscow, interrogation, and execution, with our comments. Special attention is given to a unique colored drawing, showing the brothers, Stepan and Frol Razin, as well as the body parts of the executed Stepan. From the written documents it becomes clear that the drawing was sent from Moscow to the governor of Swedish Ingria in Narva, and then forwarded to Stockholm, together with the two Koch dispatches. The authors come to the conclusion that several copies must have been made and that they were intentionally distributed among foreigners in Moscow. Most probably only one copy has survived to our days, the one in Stockholm. Arguments are given for the hypothesis that one copy of the drawing ended up in England and served as the prototype for the well-known imprint of 1672, which shows the Razin brothers when they were being delivered to Moscow. In our study we also compare the information given by Koch with descriptions of Razin’s death that were published in West-European newspapers, pamphlets, and books during the 1670s. This comparison brings us to the conclusion that the information about the execution of the leader of the rebellion reached the European press from several witnesses to the events, and that, over time, the original information was filled out with invented details.

Decreased naive and increased memory CD4(+ T cells are associated with subclinical atherosclerosis: the multi-ethnic study of atherosclerosis.

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Nels C Olson

Full Text Available Adaptive immunity has been implicated in atherosclerosis in animal models and small clinical studies. Whether chronic immune activation is associated with atherosclerosis in otherwise healthy individuals remains underexplored. We hypothesized that activation of adaptive immune responses, as reflected by higher proportions of circulating CD4(+ memory cells and lower proportions of naive cells, would be associated with subclinical atherosclerosis.We examined cross-sectional relationships of circulating CD4(+ naive and memory T cells with biomarkers of inflammation, serologies, and subclinical atherosclerosis in 912 participants of the Multi-Ethnic Study of Atherosclerosis (MESA. Circulating CD4(+ naive cells were higher in women than men and decreased with age (all p-values <0.0001. European-Americans had higher levels of naive cells and lower levels of memory cells compared with African-Americans and Hispanic-Americans (all p-values ≤0.0005. Lower naive/higher memory cells were associated with interleukin-6 levels. In multivariate models, cytomegalovirus (CMV and H. Pylori titers were strongly associated with higher memory and lower naive cells (all p-values <0.05. Higher memory cells were associated with coronary artery calcification (CAC level in the overall population [β-Coefficient (95% confidence interval (CI  = 0.20 (0.03, 0.37]. Memory and naive (inversely cells were associated with common carotid artery intimal media thickness (CC IMT in European-Americans [memory: β =  0.02 (0.006, 0.04; naive: β = -0.02 (-0.004, -0.03].These results demonstrate that the degree of chronic adaptive immune activation is associated with both CAC and CC IMT in otherwise healthy individuals, consistent with the known role of CD4(+ T cells, and with innate immunity (inflammation, in atherosclerosis. These data are also consistent with the hypothesis that immunosenescence accelerates chronic diseases by putting a greater burden on the innate

The Biochemistry of atherosclerosis

National Research Council Canada - National Science Library

Scanu, Angelo M; Getz, Godfrey S; Wissler, Robert W

1979-01-01

In this first full-length review of the biochemical parameters and their part in the pathogenesis of atherosclerosis, the reader will discover a range of coverage concerning basic etiological factors...

Atherosclerosis: the interplay between lipids and immune cells

NARCIS (Netherlands)

Schaftenaar, Frank; Frodermann, Vanessa; Kuiper, Johan; Lutgens, Esther

2016-01-01

Cardiovascular disease is the leading cause of mortality worldwide. The underlying cause of the majority of cardiovascular disease is atherosclerosis. In the past, atherosclerosis was considered to be the result of passive lipid accumulation in the vessel wall. However, today's picture of the

Imaging Macrophage and Hematopoietic Progenitor Proliferation in Atherosclerosis

DEFF Research Database (Denmark)

Ye, Yu-Xiang; Calcagno, Claudia; Binderup, Tina

2015-01-01

tomography-computed tomography imaging of cell proliferation in atherosclerosis. METHODS AND RESULTS: (18)F-FLT positron emission tomography-computed tomography was performed in mice, rabbits, and humans with atherosclerosis. In apolipoprotein E knock out mice, increased (18)F-FLT signal was observed...

Implications of alcoholic cirrhosis in atherosclerosis of autopsied patients

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Luciano Alves Matias da Silveira

Full Text Available Summary Introduction: Alcoholism is a major public health problem, which has a high social cost and affects many aspects of human activity. Liver disease is one of the first consequences of alcohol abuse, and steatosis, liver cirrhosis and hepatitis may occur. Other organs are also affected with pathological changes, such as pancreatitis, cardiomyopathies, dyslipidemias and atherosclerosis. Objective: To identify the occurrence and degree of atherosclerosis in alcohol-dependent individuals with liver cirrhosis, observing macroscopic and microscopic changes in lipid and collagen deposits and in the liver. We also aimed to verify the association of lipid and collagen fiber deposits with gender, age and body mass index, and to relate alcoholism, liver cirrhosis and atherosclerosis. Method: We performed a study based on autopsy reports of patients with alcoholic liver cirrhosis, with analysis of aorta and liver fragments to verify the occurrence and degree of atherosclerosis, as well as collagen contents. Results: Microscopic atherosclerosis was higher in young subjects (early injury and in patients with alcoholic liver cirrhosis. The macroscopic analysis of atherosclerosis in aortas showed that patients in more advanced age groups presented more severe classifications. Atherosclerosis, both micro and macroscopically, and the percentage of fibrosis in the liver and aorta were more expressive in females. Conclusion: Cirrhotic patients presented a higher percentage of fibrosis and lipidosis, and may represent a group susceptible to the accelerated progression of cardiovascular diseases. Investigative studies contribute to targeting health-promoting interventions, reducing the mortality and costs of treating cardiovascular disease.

Hepatic JAK2 protects against atherosclerosis through circulating IGF-1.

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Sivasubramaniyam, Tharini; Schroer, Stephanie A; Li, Angela; Luk, Cynthia T; Shi, Sally Yu; Besla, Rickvinder; Dodington, David W; Metherel, Adam H; Kitson, Alex P; Brunt, Jara J; Lopes, Joshua; Wagner, Kay-Uwe; Bazinet, Richard P; Bendeck, Michelle P; Robbins, Clinton S; Woo, Minna

2017-07-20

Atherosclerosis is considered both a metabolic and inflammatory disease; however, the specific tissue and signaling molecules that instigate and propagate this disease remain unclear. The liver is a central site of inflammation and lipid metabolism that is critical for atherosclerosis, and JAK2 is a key mediator of inflammation and, more recently, of hepatic lipid metabolism. However, precise effects of hepatic Jak2 on atherosclerosis remain unknown. We show here that hepatic Jak2 deficiency in atherosclerosis-prone mouse models exhibited accelerated atherosclerosis with increased plaque macrophages and decreased plaque smooth muscle cell content. JAK2's essential role in growth hormone signalling in liver that resulted in reduced IGF-1 with hepatic Jak2 deficiency played a causal role in exacerbating atherosclerosis. As such, restoring IGF-1 either pharmacologically or genetically attenuated atherosclerotic burden. Together, our data show hepatic Jak2 to play a protective role in atherogenesis through actions mediated by circulating IGF-1 and, to our knowledge, provide a novel liver-centric mechanism in atheroprotection.

Local Bone Marrow Renin-Angiotensin System and Atherosclerosis

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Yavuz Beyazit

2011-01-01

Full Text Available Local hematopoietic bone marrow (BM renin-angiotensin system (RAS affects the growth, production, proliferation differentiation, and function of hematopoietic cells. Angiotensin II (Ang II, the dominant effector peptide of the RAS, regulates cellular growth in a wide variety of tissues in pathobiological states. RAS, especially Ang II and Ang II type 1 receptor (AT1R, has considerable proinflammatory and proatherogenic effects on the vessel wall, causing progression of atherosclerosis. Recent investigations, by analyzing several BM chimeric mice whose BM cells were positive or negative for AT1R, disclosed that AT1R in BM cells participates in the pathogenesis of atherosclerosis. Therefore, AT1R blocking not only in vascular cells but also in the BM could be an important therapeutic approach to prevent atherosclerosis. The aim of this paper is to review the function of local BM RAS in the pathogenesis of atherosclerosis.

Activation of liver X receptor decreases atherosclerosis in Ldlr⁻/⁻ mice in the absence of ATP-binding cassette transporters A1 and G1 in myeloid cells

NARCIS (Netherlands)

Kappus, Mojdeh S.; Murphy, Andrew J.; Abramowicz, Sandra; Ntonga, Vusisizwe; Welch, Carrie L.; Tall, Alan R.; Westerterp, Marit

2014-01-01

Liver X receptor (LXR) activators decrease atherosclerosis in mice. LXR activators (1) directly upregulate genes involved in reverse cholesterol transport and (2) exert anti-inflammatory effects mediated by transrepression of nuclear factor-κB target genes. We investigated whether myeloid cell

Is there an association between coronary atherosclerosis and ...

African Journals Online (AJOL)

Background: Atherosclerotic disease is the most common cause of death in the United States and prostate cancer has the highest incidence among males in the United States. Reports have indicated that atherosclerosis and cancers my share common pathoetiologic and pathogenetic cascades. If atherosclerosis and ...

Suppression of atherosclerosis by synthetic REV-ERB agonist

Energy Technology Data Exchange (ETDEWEB)

Sitaula, Sadichha [Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 33458 (United States); Billon, Cyrielle [Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, MO 63104 (United States); Kamenecka, Theodore M.; Solt, Laura A. [Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 33458 (United States); Burris, Thomas P., E-mail: burristp@slu.edu [Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, MO 63104 (United States)

2015-05-08

The nuclear receptors for heme, REV-ERBα and REV-ERBβ, play important roles in the regulation of metabolism and inflammation. Recently it was demonstrated that reduced REV-ERBα expression in hematopoetic cells in LDL receptor null mice led to increased atherosclerosis. We sought to determine if synthetic REV-ERB agonists that we have developed might have the ability to suppress atherosclerosis in this model. A previously characterized synthetic REV-ERB agonist, SR9009, was used to determine if activation of REV-ERB activity would affect atherosclerosis in LDL receptor deficient mice. Atherosclerotic plaque size was significantly reduced (p < 0.05) in mice administered SR9009 (100 mg/kg) for seven weeks compared to control mice (n = 10 per group). SR9009 treatment of bone marrow-derived mouse macrophages (BMDM) reduced the polarization of BMDMs to proinflammatory M1 macrophage while increasing the polarization of BMDMs to anti-inflammatory M2 macrophages. Our results suggest that pharmacological targeting of REV-ERBs may be a viable therapeutic option for treatment of atherosclerosis. - Highlights: • Synthetic REV-ERB agonist treatment reduced atherosclerosis in a mouse model. • Pharmacological activation of REV-ERB decreased M1 macrophage polarization. • Pharmacological activation of REV-ERB increased M2 macrophage polarization.

Diet and Atherosclerosis | Grande | South African Medical Journal

African Journals Online (AJOL)

Among the various factors affecting the development of atherosclerosis and its complications, the diet emerges as an important influence. This article reviews the evidence linking diet and atherosclerosis; the relation between serum cholesterol concentration and incidence of coronary heart disease, and the effect of various ...

What Is Atherosclerosis?

Science.gov (United States)

... builds up in the renal arteries. These arteries supply oxygen-rich blood to your kidneys. Over time, chronic kidney disease causes a slow loss of kidney function. The main function of the kidneys is to remove waste and extra water from the body. Overview The cause of atherosclerosis ...

Gene expression profiling of resting and activated vascular smooth muscle cells by serial analysis of gene expression and clustering analysis

NARCIS (Netherlands)

Beauchamp, Nicholas J.; van Achterberg, Tanja A. E.; Engelse, Marten A.; Pannekoek, Hans; de Vries, Carlie J. M.

2003-01-01

Migration and proliferation of vascular smooth muscle cells (SMCs) are key events in atherosclerosis. However, little is known about alterations in gene expression upon transition of the quiescent, contractile SMC to the proliferative SMC. We performed serial analysis of gene expression (SAGE) of

Intranasal immunization with chitosan/pCETP nanoparticles inhibits atherosclerosis in a rabbit model of atherosclerosis.

Science.gov (United States)

Yuan, Xiying; Yang, Xiaorong; Cai, Danning; Mao, Dan; Wu, Jie; Zong, Li; Liu, Jingjing

2008-07-04

In search of a convenient and pain-free route of administration of DNA vaccine against atherosclerosis, the plasmid pCR-X8-HBc-CETP (pCETP) encoding B-cell epitope of cholesteryl ester transfer protein C-terminal fragment displayed by Hepatitis B virus core particle was condensed with chitosan to form chitosan/pCETP nanoparticles. Cholesterol-fed rabbits were then intranasally immunized with the chitosan/pCETP nanoparticles to evaluate antiatherogenic effects. The results showed that significant serum antibodies against CETP were detected by enzyme-linked immunosorbent analysis and verified by Western blot analysis. The significant anti-CETP IgG lasted for 21 weeks in the rabbits immunized intranasally. Moreover, the atherogenic index was significantly lower compared with the saline control (5.95 versus 2.39, pnanoparticles was 59.2% less than those treated with saline (29.0+/-10.9% versus 71.0+/-14.4%, pintramuscularly injected with pCETP solution (29.0+/-10.9% versus 21.2+/-14.2%, p>0.05). Thus, chitosan/pCETP nanoparticles could significantly attenuate the progression of atherosclerosis by intranasal immunization. The results suggested that intranasal administration could be potentially developed as a vaccination route against atherosclerosis.

C-reactive protein in relation to early atherosclerosis and periodontitis.

Science.gov (United States)

Yakob, Maha; Meurman, Jukka H; Jogestrand, Tomas; Nowak, Jacek; Söder, Per-Östen; Söder, Birgitta

2012-02-01

Periodontitis may affect atherosclerosis via the chronic inflammation. We investigated high-sensitivity C-reactive protein (hsCRP) in relation to early vascular atherosclerotic changes in non-symptomatic subjects with and without long-term periodontitis. Carotid ultrasonography with calculation of common carotid artery intima-media area (cIMA) was performed, and hsCRP and atherosclerosis risk factors were analysed in randomly chosen 93 patients with periodontitis and 41 controls. The relationship between hsCRP, cIMA and atherosclerosis risk factors was evaluated with multiple logistic regression analysis. Women displayed lower hsCRP (p periodontitis, cIMA values were higher than in controls. Periodontitis appeared to be a major predictor for increased cIMA (odds ratio, 3.82; 95% confidence interval, 1.19-12.26). Neither of these factors was significantly associated with hsCRP which thus appeared not sensitive enough to be a marker for periodontitis or atherosclerosis. Hence, irrespective of low hsCRP levels, periodontitis appeared to increase the risk for atherosclerosis.

Sexual activity as a trigger of myocardial infarction. A case-crossover analysis in the Stockholm Heart Epidemiology Programme (SHEEP)

DEFF Research Database (Denmark)

Möller, J; Ahlbom, A; Hulting, J

2001-01-01

.9). CONCLUSIONS: The increased risk of myocardial infarction after sexual activity and the further increase in risk among the less physically fit support the hypothesis of causal triggering by sexual activity. However, the absolute risk per hour is very low, and exposure is relatively infrequent. Thus having sex......OBJECTIVE: To investigate sexual activity as a trigger of myocardial infarction and the potential effect modification of physical fitness. DESIGN: A case-crossover study nested in the Stockholm Heart Epidemiology Programme (SHEEP). SETTING: Stockholm County from April 1993 to December 1994...... once a week only increases the annual risk of myocardial infarction slightly. Counselling should focus on encouraging patients to live a physically active life and not on abstaining from sexual activity....

Coronary atherosclerosis in medico-legal autopsy cases

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VN Prasad

2014-09-01

Full Text Available Background: Coronary atherosclerosis is the major cause of death worldwide. Lifestyle and habits are the major contributory factor in the development of coronary atherosclerosis. Materials and Methods: This is an autopsy-based study in which 45 autopsy cases were randomly selected for study. Proximal one third of all three epicardial coronary arteries (LAD, LCX and RCA were dissected out for study and serial sections were made and stained with H&E method and under the light microscope. Atherosclerosis was graded according to American heart association classification. The risk factors (cigarette smoking, hypertension, diabetes, alcohol consumption, age, sex were also correlated with the grade of atherosclerosis. Results: Seventy-Eight percent of American Heart Association classification grade V lesions were seen in > 70 yrs of age. Almost all cases of > 70 yrs of age had American Heart Association classification grade > IV lesions. Out of all grade IV lesions, 88.9% was seen in male while only 11.1% in female. Similarly out of all grade V lesions, 77.8% was seen in male while 22.2% in female. LAD showed maximum involvement by higher grade lesion, followed by LCX and RCA. American Heart Association classification grade > IV in LAD, LCX and RCA was seen in 25(55.6%, 5(11.1%, and 3(6.7% cases respectively. Conclusion: Higher grade lesion occurs in advancing age. Various cardiovascular risk factors were significantly associated with higher grade of lesions. The multiple risk factors had a synergistic effect on the progression of coronary atherosclerosis. DOI: http://dx.doi.org/10.3126/jpn.v4i8.11492 Journal of Pathology of Nepal; Vol.4,No8(2014 607-611

Datasets for the validation of the "in vivo" siRNA-silencing of CD40 and for the detection of new markers of atherosclerosis progression in ApoE-deficient mice

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Miguel Hueso

2016-12-01

Full Text Available Data presented in this Data in Brief article correspond to the article "in vivo" silencing of CD40 reduces progression of experimental atherogenesis through a NFκB/miR-125b axis and reveals new potential mediators in the pathogenesis of atherosclerosis" (M. Hueso, L. De Ramon, E. Navarro, E. Ripoll, J.M. Cruzado, J.M. Grinyo, J. Torras, 2016 [1]. Here, we describe the validation of the silencing of CD40 expression with a specific siRNA in ApoE−/− mouse aortas, and its systemic effects on splenic lymphocytic subpopulations as well as on the infiltration of aortic intima by F4/80+, galectin-3+ macrophages or by NF-κB+ cells. We also show the output of a Gene Ontology and TLDA analysis which allowed the detection of potential mediators of atherosclerosis progression. We provide the scientific community with a set of genes whose expression is increased during atherosclerosis progression but downregulated upon CD40 silencing.

Targeting the adaptive immune system: new strategies in the treatment of atherosclerosis

NARCIS (Netherlands)

Zarzycka, Barbara; Nicolaes, Gerry A. F.; Lutgens, Esther

2015-01-01

Atherosclerosis is a lipid-driven chronic inflammatory disease of the arterial wall. Current treatment of atherosclerosis is focused on limiting its risk factors, such as hyperlipidemia or hypertension. However, treatments that target the inflammatory nature of atherosclerosis are still under

Periodontal disease and carotid atherosclerosis: A meta-analysis of 17,330 participants.

Science.gov (United States)

Zeng, Xian-Tao; Leng, Wei-Dong; Lam, Yat-Yin; Yan, Bryan P; Wei, Xue-Mei; Weng, Hong; Kwong, Joey S W

2016-01-15

The association between periodontal disease and carotid atherosclerosis has been evaluated primarily in single-center studies, and whether periodontal disease is an independent risk factor of carotid atherosclerosis remains uncertain. This meta-analysis aimed to evaluate the association between periodontal disease and carotid atherosclerosis. We searched PubMed and Embase for relevant observational studies up to February 20, 2015. Two authors independently extracted data from included studies, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for overall and subgroup meta-analyses. Statistical heterogeneity was assessed by the chi-squared test (Pperiodontal disease was associated with carotid atherosclerosis (OR: 1.27, 95% CI: 1.14-1.41; Pperiodontal disease was associated with carotid atherosclerosis; however, further large-scale, well-conducted clinical studies are needed to explore the precise risk of developing carotid atherosclerosis in patients with periodontal disease. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Apolipoprotein E deficiency increases remnant lipoproteins and accelerates progressive atherosclerosis, but not xanthoma formation, in gene modified minipigs

DEFF Research Database (Denmark)

Shim, Jeong; Poulsen, Christian Bo; Hagensen, Mette K.

2017-01-01

Summary: Deficiency of apolipoprotein E (APOE) causes familial dysbetalipoproteinemia in humans resulting in a higher risk of atherosclerotic disease. In mice, APOE deficiency results in a severe atherosclerosis phenotype, but it is unknown to what extent this is unique to mice. In this study, AP...

Macrophage Phenotype and Function in Different Stages of Atherosclerosis

Science.gov (United States)

Tabas, Ira; Bornfeldt, Karin E.

2016-01-01

The remarkable plasticity and plethora of biological functions performed by macrophages have enticed scientists to study these cells in relation to atherosclerosis for more than 50 years, and major discoveries continue to be made today. It is now understood that macrophages play important roles in all stages of atherosclerosis, from initiation of lesions and lesion expansion, to necrosis leading to rupture and the clinical manifestations of atherosclerosis, to resolution and regression of atherosclerotic lesions. Lesional macrophages are derived primarily from blood monocytes, although recent research has shown that lesional macrophage-like cells can also be derived from smooth muscle cells. Lesional macrophages take on different phenotypes depending on their environment and which intracellular signaling pathways are activated. Rather than a few distinct populations of macrophages, the phenotype of the lesional macrophage is more complex and likely changes during the different phases of atherosclerosis and with the extent of lipid and cholesterol loading, activation by a plethora of receptors, and metabolic state of the cells. These different phenotypes allow the macrophage to engulf lipids, dead cells, and other substances perceived as danger signals; efflux cholesterol to HDL; proliferate and migrate; undergo apoptosis and death; and secrete a large number of inflammatory and pro-resolving molecules. This review article, part of the Compendium on Atherosclerosis, discusses recent advances in our understanding of lesional macrophage phenotype and function in different stages of atherosclerosis. With the increasing understanding of the roles of lesional macrophages, new research areas and treatment strategies are beginning to emerge. PMID:26892964

Therapeutic Efficacy of an ω-3-Fatty Acid-Containing 17-β Estradiol Nano-Delivery System against Experimental Atherosclerosis.

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Dipti Deshpande

Full Text Available Atherosclerosis and its consequences remain prevalent clinical challenges throughout the world. Initiation and progression of atherosclerosis involves a complex, dynamic interplay among inflammation, hyperlipidemia, and endothelial dysfunction. A multicomponent treatment approach targeted for delivery within diseased vessels could prove beneficial in treating atherosclerosis. This study was undertaken to evaluate the multimodal effects of a novel ω-3-fatty acid-rich, 17-β-estradiol (17-βE-loaded, CREKA-peptide-modified nanoemulsion system on experimental atherosclerosis. In vitro treatment of cultured human aortic endothelial cells (ECs with the 17-βE-loaded, CREKA-peptide-modified nanoemulsion system increased cellular nitrate/nitrite, indicating improved nitric oxide formation. In vivo, systemic administration of this nanoemulsion system to apolipoprotein-E knock out (ApoE-/- mice fed a high-fat diet significantly improved multiple parameters related to the etiology and development of occlusive atherosclerotic vasculopathy: lesion area, circulating plasma lipid levels, and expression of aortic-wall inflammatory markers. These salutary effects were attributed selectively to the 17-βE and/or ω-3 polyunsaturated fatty acid components of the nano-delivery system. At therapeutic doses, the 17-βE-loaded, CREKA-peptide modified nanoemulsion system appeared to be biocompatible in that it elicited no apparent adverse/toxic effects, as indexed by body weight, plasma alanine aminotransferase/aspartate aminotransferase levels, and liver and kidney histopathology. The study demonstrates the therapeutic potential of a novel, 17-βE-loaded, CREKA-peptide-modified nanoemulsion system against atherosclerosis in a multimodal fashion by reducing lesion size, lowering the levels of circulating plasma lipids and decreasing the gene expression of inflammatory markers associated with the disease.

Apolipoprotein E and carotid artery atherosclerosis - The Rotterdam study

NARCIS (Netherlands)

Slooter, AJC; Bots, ML; Havekes, LM; del Sol, AI; Cruts, M; Grobbee, DE; Hofman, A; Van Broeckhoven, C; Witteman, JCM; van Duijn, CM

Background and Purpose-Carotid artery atherosclerosis is a strong predictor for future stroke. It is yet unclear whether the apolipoprotein E polymorphism (APOE) is related to atherosclerosis in the carotid arteries. The aim of the present study was to investigate the role of APOE in carotid artery

Extracranial cerebral arterial atherosclerosis in Iranian patients suffering ischemic strokes

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Sayed Ali Mousavi

2006-12-01

Full Text Available BACKGROUND: To determine the distribution and severity of extracranial carotid arterial atherosclerosis in Iranian patients with ischemic stroke. METHODS: 328 patients with ischemic stroke were included in this study. Doppler ultrasound was used for evaluation of atherosclerosis in extracranial carotid arteries. The NASCET criteria were used to measure carotid stenosis. RESULTS: Ninety of 328 patients (27.4% were found to have atherosclerotic plaques; 40 of these patients were women and 50 were men. Sixty-eight patients (20.7% had artery stenosis <50%, 13 patients (3.95% had 50-70 % artery stenosis and 6 (1.8% had >70% artery stenosis. CONCLUSIONS: Extracranial atherosclerosis is not rare in Iranian patients with ischemic stroke, but most carotid artery lesions were plaques with <50% stenosis. KEY WORDS: Atherosclerosis, ischemic stroke, carotid stenosis.

Osteocalcin expression by circulating endothelial progenitor cells in patients with coronary atherosclerosis.

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Gössl, Mario; Mödder, Ulrike I; Atkinson, Elizabeth J; Lerman, Amir; Khosla, Sundeep

2008-10-14

This study was designed to test whether patients with coronary atherosclerosis have increases in circulating endothelial progenitor cells (EPCs) expressing an osteogenic phenotype. Increasing evidence indicates a link between bone and the vasculature, and bone marrow and circulating osteogenic cells have been identified by staining for the osteoblastic marker, osteocalcin (OCN). Endothelial progenitor cells contribute to vascular repair, but repair of vascular injury may result in calcification. Using cell surface markers (CD34, CD133, kinase insert domain receptor [KDR]) to identify EPCs, we examined whether patients with coronary atherosclerosis had increases in the percentage of EPCs expressing OCN. We studied 72 patients undergoing invasive coronary assessment: control patients (normal coronary arteries and no endothelial dysfunction, n = 21) versus 2 groups with coronary atherosclerosis-early coronary atherosclerosis (normal coronary arteries but with endothelial dysfunction, n = 22) and late coronary atherosclerosis (severe, multivessel coronary artery disease, n = 29). Peripheral blood mononuclear cells were analyzed using flow cytometry. Compared with control patients, patients with early or late coronary atherosclerosis had significant increases (approximately 2-fold) in the percentage of CD34+/KDR+ and CD34+/CD133+/KDR+ cells costaining for OCN. Even larger increases were noted in the early and late coronary atherosclerosis patients in the percentage of CD34+/CD133-/KDR+ cells costaining for OCN (5- and 2-fold, p < 0.001 and 0.05, respectively). A higher percentage of EPCs express OCN in patients with coronary atherosclerosis compared with subjects with normal endothelial function and no structural coronary artery disease. These findings have potential implications for the mechanisms of vascular calcification and for the development of novel markers for coronary atherosclerosis.

Cellular and Molecular Mechanisms of Diabetic Atherosclerosis: Herbal Medicines as a Potential Therapeutic Approach

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Jinfan Tian

2017-01-01

Full Text Available An increasing number of patients diagnosed with diabetes mellitus eventually develop severe coronary atherosclerosis disease. Both type 1 and type 2 diabetes mellitus increase the risk of cardiovascular disease associated with atherosclerosis. The cellular and molecular mechanisms affecting the incidence of diabetic atherosclerosis are still unclear, as are appropriate strategies for the prevention and treatment of diabetic atherosclerosis. In this review, we discuss progress in the study of herbs as potential therapeutic agents for diabetic atherosclerosis.

Effects of High Fat Feeding and Diabetes on Regression of Atherosclerosis Induced by Low-Density Lipoprotein Receptor Gene Therapy in LDL Receptor-Deficient Mice.

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Florian Willecke

Full Text Available We tested whether a high fat diet (HFD containing the inflammatory dietary fatty acid palmitate or insulin deficient diabetes altered the remodeling of atherosclerotic plaques in LDL receptor knockout (Ldlr-/- mice. Cholesterol reduction was achieved by using a helper-dependent adenovirus (HDAd carrying the gene for the low-density lipoprotein receptor (Ldlr; HDAd-LDLR. After injection of the HDAd-LDLR, mice consuming either HFD, which led to insulin resistance but not hyperglycemia, or low fat diet (LFD, showed regression compared to baseline. However there was no difference between the two groups in terms of atherosclerotic lesion size, or CD68+ cell and lipid content. Because of the lack of effects of these two diets, we then tested whether viral-mediated cholesterol reduction would lead to defective regression in mice with greater hyperglycemia. In both normoglycemic and streptozotocin (STZ-treated hyperglycemic mice, HDAd-LDLR significantly reduced plasma cholesterol levels, decreased atherosclerotic lesion size, reduced macrophage area and lipid content, and increased collagen content of plaque in the aortic sinus. However, reductions in anti-inflammatory and ER stress-related genes were less pronounced in STZ-diabetic mice compared to non-diabetic mice. In conclusion, HDAd-mediated Ldlr gene therapy is an effective and simple method to induce atherosclerosis regression in Ldlr-/- mice in different metabolic states.

CDKN2B expression and subcutaneous adipose tissue expandability: Possible influence of the 9p21 atherosclerosis locus

Energy Technology Data Exchange (ETDEWEB)

Svensson, Per-Arne; Wahlstrand, Björn; Olsson, Maja [Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg (Sweden); Froguel, Philippe; Falchi, Mario [Department of Genomics of Common Disease, School of Public Health, Imperial College London (United Kingdom); Bergman, Richard N. [Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA (United States); McTernan, Philip G. [Division of Metabolic and Vascular Health, Warwick Medical School, University of Warwick, Coventry (United Kingdom); Hedner, Thomas; Carlsson, Lena M.S. [Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg (Sweden); Jacobson, Peter, E-mail: peter.jacobson@medfak.gu.se [Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg (Sweden)

2014-04-18

Highlights: • The tumor suppressor gene CDKN2B is highly expressed in human adipose tissue. • Risk alleles at the 9p21 locus modify CDKN2B expression in a BMI-dependent fashion. • There is an inverse relationship between expression of CDKN2B and adipogenic genes. • CDKN2B expression influences to postprandial triacylglycerol clearance. • CDKN2B expression in adipose tissue is linked to markers of hepatic steatosis. - Abstract: Risk alleles within a gene desert at the 9p21 locus constitute the most prevalent genetic determinant of cardiovascular disease. Previous research has demonstrated that 9p21 risk variants influence gene expression in vascular tissues, yet the biological mechanisms by which this would mediate atherosclerosis merits further investigation. To investigate possible influences of this locus on other tissues, we explored expression patterns of 9p21-regulated genes in a panel of multiple human tissues and found that the tumor suppressor CDKN2B was highly expressed in subcutaneous adipose tissue (SAT). CDKN2B expression was regulated by obesity status, and this effect was stronger in carriers of 9p21 risk alleles. Covariation between expression of CDKN2B and genes implemented in adipogenesis was consistent with an inhibitory effect of CDKN2B on SAT proliferation. Moreover, studies of postprandial triacylglycerol clearance indicated that CDKN2B is involved in down-regulation of SAT fatty acid trafficking. CDKN2B expression in SAT correlated with indicators of ectopic fat accumulation, including markers of hepatic steatosis. Among genes regulated by 9p21 risk variants, CDKN2B appears to play a significant role in the regulation of SAT expandability, which is a strong determinant of lipotoxicity and therefore might contribute to the development of atherosclerosis.

Komentovaný překlad: Love and Stockholm Syndrome: The Mystery of Loving an Abuser. Joe Carver, PhD. http: drjoecarver.makeswebsites.com/clients/49355/File/love_and_stockholm_syndrome.html

OpenAIRE

Vašková, Adéla

2013-01-01

This bachelor's thesis consists of a Czech translation of an article Love and Stockholm Syndrome: The Mystery of Loving an Abuser written by an american author Joseph Carver, Ph.D., and a commentary on the translation. The commentary is divided into four parts: an analysis of the source text based on the model of Christiane Nord, the translation problems and their solutions, typology of the translation shifts based on the theory of Anton Popovič and the chosen translation method.

Frequency of Subclinical Atherosclerosis in Brazilian HIV-Infected Patients.

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Salmazo, Péricles Sidnei; Bazan, Silméia Garcia Zanati; Shiraishi, Flávio Gobbis; Bazan, Rodrigo; Okoshi, Katashi; Hueb, João Carlos

2018-04-09

AIDS as well as atherosclerosis are important public health problems. The longer survival among HIV-infected is associated with increased number of cardiovascular events in this population, and this association is not fully understood. To identify the frequency of subclinical atherosclerosis in HIV-infected patients compared to control subjects; to analyze associations between atherosclerosis and clinical and laboratory variables, cardiovascular risk factors, and the Framingham coronary heart disease risk score (FCRS). Prospective cross-sectional case-control study assessing the presence of subclinical atherosclerosis in 264 HIV-infected patients and 279 controls. Clinical evaluation included ultrasound examination of the carotid arteries, arterial stiffness by pulse wave velocity (PWV) and augmentation index (AIx), laboratory analysis of peripheral blood, and cardiovascular risk according to FCRS criteria. The significance level adopted in the statistical analysis was p media thickness was higher in the HIV group than in controls (p media thickness, was not associated with carotid plaque frequency, and did not alter the mechanical characteristics of the arterial system (PWV and AIx). HIV-infected patients are at increased risk of atherosclerosis in association with classical cardiovascular risk factors. Treatment with protease inhibitors does not promote functional changes in the arteries, and shows no association with increased frequency of atherosclerotic plaques in carotid arteries. The FCRS may be inappropriate for this population.

Intracranial atherosclerosis: current concepts.

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Arenillas, Juan F

2011-01-01

The most relevant ideas discussed in this article are described here. Intracranial atherosclerotic disease (ICAD) represents the most common cause of ischemic stroke worldwide. Its importance in whites may have been underestimated. New technical developments, such as high-resolution MRI, allow direct assessment of the intracranial atherosclerotic plaque, which may have a profound impact on ICAD diagnosis and therapy in the near future. Early detection of ICAD may allow therapeutic intervention while the disease is still asymptomatic. The Barcelonès Nord and Maresme Asymptomatic Intracranial Atherosclerosis Study is presented here. The main prognostic factors that characterize the patients who are at a higher risk for ICAD recurrence are classified and discussed. The best treatment for ICAD remains to be established. The Stenting Versus Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis Study is currently ongoing to address this crucial issue. These and other topics will be discussed at the Fifth International Intracranial Atherosclerosis Conference (Valladolid, Spain, autumn 2011).

Gender-Related Differences in Atherosclerosis

Czech Academy of Sciences Publication Activity Database

Mathur, P.; Ošťádal, Bohuslav; Romeo, F.; Mehta, J. L.

2015-01-01

Roč. 29, č. 4 (2015), s. 319-327 ISSN 0920-3206 Institutional support: RVO:67985823 Keywords : atherosclerosis * gender Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 3.189, year: 2015

Improved survival after an educational project on colon cancer management in the county of Stockholm--a population based cohort study.

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Bernhoff, R; Martling, A; Sjövall, A; Granath, F; Hohenberger, W; Holm, T

2015-11-01

Outcomes in rectal cancer have improved dramatically after the introduction of total mesorectal excision (TME). Recently, the TME concept has been transformed into that of complete mesocolic excision (CME) in an attempt to improve prognosis for patients with colon cancer. Multidisciplinary team (MDT) workshops including the CME concept were held annually between 2004 and 2008 at the Karolinska University Hospital. The workshops focused on preoperative staging, surgery and histopathology and included lectures and live surgery sessions. To compare survival before and after the "Stockholm Colon Cancer Project" all patients diagnosed with a right sided colon cancer between January 1, 2001 and December 31, 2003 (Group 1) and from January 1, 2006 until December 31, 2008 (Group 2) in Stockholm were identified from the Swedish ColoRectal Cancer Registry (SCRCR). The proportion of patients having a tumour resection and the proportion having emergency surgery was higher in Group 1. There were more early tumours and more R0 resections in Group 2. Overall survival in all diagnosed patients and disease free survival after tumour resection was improved in the second time period. Surgical teaching programmes may have an impact on the management and outcome in colon cancer. The exact impact from the "Stockholm Colon Cancer Project" cannot be established, however it is likely that it contributed to the improved survival. Copyright © 2015 Elsevier Ltd. All rights reserved.

Basic mechanisms in intracranial large-artery atherosclerosis: advances and challenges.

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Arenillas, Juan F; Alvarez-Sabín, José

2005-01-01

Intracranial large-artery atherosclerosis is a major cause of ischemic stroke worldwide. Patients affected by this disease are at a high risk of suffering recurrent ischemic events despite antithrombotic therapy. Progression and a greater extent of intracranial atherosclerosis imply a higher risk for recurrence. Studies performed by our group in patients with symptomatic intracranial large-artery atherosclerosis have shown that: (1) C-reactive protein predicts its progression and recurrence, suggesting that inflammation may play a deleterious role in this condition; (2) a high level of the anti-angiogenic endostatin is also associated with a progressive and recurrent intracranial atherosclerosis, which might support a beneficial role for angiogenesis in this group of patients; and (3) elevated lipoprotein(a) concentration and diabetes mellitus characterize those patients with a higher number of intracranial stenoses. 2005 S. Karger AG, Basel

Altered Clock and Lipid Metabolism-Related Genes in Atherosclerotic Mice Kept with Abnormal Lighting Condition

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Zhu Zhu

2016-01-01

Full Text Available Background. The risk of atherosclerosis is elevated in abnormal lipid metabolism and circadian rhythm disorder. We investigated whether abnormal lighting condition would have influenced the circadian expression of clock genes and clock-controlled lipid metabolism-related genes in ApoE-KO mice. Methods. A mouse model of atherosclerosis with circadian clock genes expression disorder was established using ApoE-KO mice (ApoE-KO LD/DL mice by altering exposure to light. C57 BL/6J mice (C57 mice and ApoE-KO mice (ApoE-KO mice exposed to normal day and night and normal diet served as control mice. According to zeitgeber time samples were acquired, to test atheromatous plaque formation, serum lipids levels and rhythmicity, clock genes, and lipid metabolism-related genes along with Sirtuin 1 (Sirt1 levels and rhythmicity. Results. Atherosclerosis plaques were formed in the aortic arch of ApoE-KO LD/DL mice. The serum lipids levels and oscillations in ApoE-KO LD/DL mice were altered, along with the levels and diurnal oscillations of circadian genes, lipid metabolism-associated genes, and Sirt1 compared with the control mice. Conclusions. Abnormal exposure to light aggravated plaque formation and exacerbated disorders of serum lipids and clock genes, lipid metabolism genes and Sirt1 levels, and circadian oscillation.

Coronary atherosclerosis: Significance of autophagic armour.

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Arora, Mansi; Kaul, Deepak

2012-09-26

Autophagy is a lysosomal degradation pathway of cellular components such as organelles and long-lived proteins. Though a protective role for autophagy has been established in various patho-physiologic conditions such as cancer, neurodegeneration, aging and heart failure, a growing body of evidence now reveals a protective role for autophagy in atherosclerosis, mainly by removing oxidatively damaged organelles and proteins and also by promoting cholesterol egress from the lipid-laden cells. Recent studies by Razani et al and Liao et al unravel novel pathways that might be involved in autophagic protection and in this commentary we highlight the importance of autophagy in atherosclerosis in the light of these two recent papers.

Atherosclerosis induced by arsenic in drinking water in rats through altering lipid metabolism

International Nuclear Information System (INIS)

Cheng, Tain-Junn; Chuu, Jiunn-Jye; Chang, Chia-Yu; Tsai, Wan-Chen; Chen, Kuan-Jung; Guo, How-Ran

2011-01-01

Arsenic in drinking water is a global environmental health problem, and the exposure may increase cardiovascular and cerebrovascular diseases mortalities, most likely through causing atherosclerosis. However, the mechanism of atherosclerosis formation after arsenic exposure is still unclear. To study the mechanism of atherosclerosis formation after arsenic exposure and explore the role of high cholesterol diet (HCD) in this process, we fed spontaneous hypertensive rats and Wistar Kyoto rats with basal diet or HCD and provided with them drinking water containing arsenic at different ages and orders for 20 consecutive weeks. We measured high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, heat shock protein 70 (HSP 70), and high sensitive C-reactive protein (hs-CRP) at predetermined intervals and determined expressions of cholesteryl ester transfer protein-1 (CETP-1) and liver X receptor β (LXRβ) in the liver. Atherosclerosis was determined by examining the aorta with hematoxylin and eosin stain. After 20 weeks, we found arsenic, alone or combined with HCD, may promote atherosclerosis formation with transient increases in HSP 70 and hs-CRP. Early combination exposure decreased the HDL-C/LDL-C ratio without changing the levels of total cholesterol and triglyceride until 30 weeks old. Both CETP-1 and LXRβ activities were suppressed, most significantly in early combination exposure. In conclusion, arsenic exposure may induce atherosclerosis through modifying reverse cholesterol transport in cholesterol metabolism and suppressing LXRβ and CEPT-1 expressions. For decreasing atherosclerosis related mortality associated with arsenic, preventing exposure from environmental sources in early life is an important element. - Highlights: → Arsenic causes cardiovascular and cerebrovascular diseases through atherosclerosis. → Arsenic may promote atherosclerosis with transient increase in HSP 70 and hs

Association between nucleotide mutation of eNOS gene and serum ...

African Journals Online (AJOL)

Various mutation on endothelial nitric oxide synthase (eNOs) gene cause reduced production of NO, the expansion factor (VEF) and may accelerate the process of atherosclerosis. The study was designed to investigate the frequency of T-786C polymorphism of the gene or nucleotide mutation of eNOS gene in patients ...

From research institution to astronomical museum: a history of the Stockholm Observatory

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Yaskell, Steven Haywood

2008-07-01

The Royal Swedish Academy of Sciences (RSAS) (or Kungliga Vetenskapsakademien [KvA] in Swedish) founded 1739, opened its first permanent building, an astronomical and meteorological observatory, on 20 September 1753. This was situated at Brunkebergsåsen (formerly Observatorie Lunden, or Observatory Hill), on a high terrace in a northern quarter of Stockholm. This historic building is still sometimes called Gamla Observatoriet (the Old Observatory) and now is formally the Observatory Museum. This paper reviews the history of the Observatory from its function as a scientific astronomical institution to its relatively-recent relegation to museum status.

A review of plant-based compounds and medicinal plants effective on atherosclerosis

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Mehrnoosh Sedighi

2017-01-01

Full Text Available Atherosclerosis is one of the most important cardiovascular diseases that involve vessels through the development of fatty streaks and plaques. Plant-based compounds can help treat or prevent atherosclerosis through affecting the involved factors. The main purpose of this review article is to investigate and introduce medicinal plants and their potential activities regarding antioxidant properties, effective on lipids level and development of plaque, atherosclerosis, and progression of atherosclerosis as well as the development of cardiovascular disease and ischemia. To search for the relevant articles indexed in Information Sciences Institute, PubMed, Scientific Information Database, IranMedex, and Scopus between 1980 and 2013, with further emphasis on those indexed from 2004 to 2015, we used these search terms: atherosclerosis, antioxidant, cholesterol, inflammation, and the medicinal plants below. Then, the articles with inclusion criteria were used in the final analysis of the findings. Plant-based active compounds, including phenols, flavonoids, and antioxidants, can be effective on atherosclerosis predisposing factors and hence in preventing this disease and associated harmful complications, especially through reducing cholesterol, preventing increase in free radicals, and ultimately decreasing vascular plaque and vascular resistance. Hence, medicinal plants can contribute to treating atherosclerosis and preventing its progression through reducing cholesterolemia, free radicals, inflammation, vascular resistance, and certain enzymes. They, alone or in combination with hypocholesterolemic drugs, can therefore be useful for patients with hyperlipidemia and its complications.

Arterial scleroproteins in atherosclerosis and hypertension (Experimental studies)

International Nuclear Information System (INIS)

Yurukova, Ts.; Georgiev, P.

1979-01-01

The authors studied the neosynthesis of fiber protein (scleroproteins) in the aorta of rats with genetic hypertension and with experimental atherosclerosis following application of 3 H-proline and 3 H-lysine and subsequent determination of radioactivity of the collagen and elastic fractions of the aortic wall. There was a great increase in incorporation of labelled collagen and elastin precursors in the aorta of hypertensive and atherosclerotic animals, in comparison with the control rats - a manifestation of incresed ''de novo'' synthesis of fiber proteins in rats with these arterial diseases. Furthermore, the increased collagenosis dominated over that of elastogenesis. The irregular activation of the biosynthesis of both scleroproteins in hypertensive rats and in rats with atherosclerosis caused remodelling of the macromolecular structure of the arterial wall with predominance of collagen over the remaining hypertension components and progression of atherosclerosis. (author) (author)

Apple Polyphenols Decrease Atherosclerosis and Hepatic Steatosis in ApoE-/- Mice through the ROS/MAPK/NF-κB Pathway.

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Xu, Zhe-Rong; Li, Jin-You; Dong, Xin-Wei; Tan, Zhong-Ju; Wu, Wei-Zhen; Xie, Qiang-Min; Yang, Yun-Mei

2015-08-24

In this study, we examined the effects of apple polyphenols (APs) on hyperlipidemia, atherosclerosis, hepatic steatosis and endothelial function and investigated the potential mechanisms. ApoE(-/-) mice were fed a western-type diet and orally treated with APs (100 mg/kg) or atorvastatin (10 mg/kg) for 12 weeks. Hyperlipidemia and atherosclerosis in the aortic sinuses and, and hepatic lipidosis were measured. The treatment with APs or atorvastatin induced a remarkable reduction in the atherosclerotic lesions and hepatic steatosis and decreased the levels of low-density lipoprotein, triglyceride, CCL-2 and VCAM-1 levels in the plasma. Conversely, the APs significantly increased the plasma levels of high-density lipoprotein (HDL) cholesterol and markedly up-regulated the glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) levels in liver tissues. Moreover, the APs treatment modulated lipid metabolism by up-regulating the transcription of associated hepatic genes including PPARα, while down-regulating the transcription of SCAP and its downstream genes associated with lipid synthesis in the liver. Histological assessment showed that the APs treatment also reduced the macrophage infiltration in the aortic root plaque and the inflammatory cells infiltrations to the liver tissues. Moreover, we confirmed that the APs treatment greatly reduced the ox-LDL-induced endothelial dysfunction and monocyte adhesion to rat aortic endothelial cells (RAECs). Mechanistically, the APs treatment suppressed the ROS/MAPK/NF-κB signaling pathway, and consequently, reduced CCL-2, ICAM-1 and VCAM-1 expression. Our results suggest that the APs are a beneficial nutritional supplement for the attenuation of atherosclerosis.

The biology of atherosclerosis: general paradigms and distinct pathogenic mechanisms among HIV-infected patients.

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Lo, Janet; Plutzky, Jorge

2012-06-01

Complications of atherosclerosis, including myocardial infarction and stroke, are the leading cause of death and disability worldwide. Recent data strongly implicate cardiovascular death as a contributor to mortality among patients with human immunodeficiency virus (HIV) infection, with evidence suggesting increased incidence of atherosclerosis among these patients. Therefore, greater understanding of atherosclerotic mechanisms and how these responses may be similar or distinct in HIV-infected patients is needed. Key concepts in atherosclerosis are reviewed, including the evidence that inflammation and abnormal metabolism are major drivers of atherosclerosis, and connected to the current literature regarding atherosclerosis in the context of HIV.

Liraglutide Reduces Both Atherosclerosis and Kidney Inflammation in Moderately Uremic LDLr-/- Mice.

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Line S Bisgaard

Full Text Available Chronic kidney disease (CKD leads to uremia. CKD is characterized by a gradual increase in kidney fibrosis and loss of kidney function, which is associated with a progressive increase in risk of atherosclerosis and cardiovascular death. To prevent progression of both kidney fibrosis and atherosclerosis in uremic settings, insight into new treatment options with effects on both parameters is warranted. The GLP-1 analogue liraglutide improves glucose homeostasis, and is approved for treatment of type 2 diabetes. Animal studies suggest that GLP-1 also dampens inflammation and atherosclerosis. Our aim was to examine effects of liraglutide on kidney fibrosis and atherosclerosis in a mouse model of moderate uremia (5/6 nephrectomy (NX. Uremic (n = 29 and sham-operated (n = 14 atherosclerosis-prone low density lipoprotein receptor knockout mice were treated with liraglutide (1000 μg/kg, s.c. once daily or vehicle for 13 weeks. As expected, uremia increased aortic atherosclerosis. In the remnant kidneys from NX mice, flow cytometry revealed an increase in the number of monocyte-like cells (CD68+F4/80-, CD4+, and CD8+ T-cells, suggesting that moderate uremia induced kidney inflammation. Furthermore, markers of fibrosis (i.e. Col1a1 and Col3a1 were upregulated, and histological examinations showed increased glomerular diameter in NX mice. Importantly, liraglutide treatment attenuated atherosclerosis (~40%, p < 0.05 and reduced kidney inflammation in NX mice. There was no effect of liraglutide on expression of fibrosis markers and/or kidney histology. This study suggests that liraglutide has beneficial effects in a mouse model of moderate uremia by reducing atherosclerosis and attenuating kidney inflammation.

MicroRNA-30c Mimic Mitigates Hypercholesterolemia and Atherosclerosis in Mice*

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Irani, Sara; Pan, Xiaoyue; Peck, Bailey C. E.; Iqbal, Jahangir; Sethupathy, Praveen; Hussain, M. Mahmood

2016-01-01

High plasma cholesterol levels are a major risk factor for atherosclerosis. Plasma cholesterol can be reduced by inhibiting lipoprotein production; however, this is associated with steatosis. Previously we showed that lentivirally mediated hepatic expression of microRNA-30c (miR-30c) reduced hyperlipidemia and atherosclerosis in mice without causing hepatosteatosis. Because viral therapy would be formidable, we examined whether a miR-30c mimic can be used to mitigate hyperlipidemia and atherosclerosis without inducing steatosis. Delivery of a miR-30c mimic to the liver diminished diet-induced hypercholesterolemia in C57BL/6J mice. Reductions in plasma cholesterol levels were significantly correlated with increases in hepatic miR-30c levels. Long term dose escalation studies showed that miR-30c mimic caused sustained reductions in plasma cholesterol with no obvious side effects. Furthermore, miR-30c mimic significantly reduced hypercholesterolemia and atherosclerosis in Apoe−/− mice. Mechanistic studies showed that miR-30c mimic had no effect on LDL clearance but reduced lipoprotein production by down-regulating microsomal triglyceride transfer protein expression. MiR-30c had no effect on fatty acid oxidation but reduced lipid synthesis. Additionally, whole transcriptome analysis revealed that miR-30c mimic significantly down-regulated hepatic lipid synthesis pathways. Therefore, miR-30c lowers plasma cholesterol and mitigates atherosclerosis by reducing microsomal triglyceride transfer protein expression and lipoprotein production and avoids steatosis by diminishing lipid syntheses. It mitigates atherosclerosis most likely by reducing lipoprotein production and plasma cholesterol. These findings establish that increasing hepatic miR-30c levels is a viable treatment option for reducing hypercholesterolemia and atherosclerosis. PMID:27365390

Insulin decreases atherosclerosis by inducing endothelin receptor B expression

DEFF Research Database (Denmark)

Park, Kyoungmin; Mima, Akira; Li, Qian

2016-01-01

Endothelial cell (EC) insulin resistance and dysfunction, caused by diabetes, accelerates atherosclerosis. It is unknown whether specifically enhancing EC-targeted insulin action can decrease atherosclerosis in diabetes. Accordingly, overexpressing insulin receptor substrate-1 (IRS1...... induction of NO action, which increases endothelin receptor B (EDNRB) expression and intracellular [Ca(2+)]. Using the mice with knockin mutation of eNOS, which had Ser1176 mutated to alanine (AKI), deleting the only known mechanism for insulin to activate eNOS/NO pathway, we observed that IRS1...... overexpression in the endothelia of Aki/ApoE(-/-) mice significantly decreased atherosclerosis. Interestingly, endothelial EDNRB expression was selectively reduced in intima of arteries from diabetic patients and rodents. However, endothelial EDNRB expression was upregulated by insulin via P13K/Akt pathway...

Atherosclerosis in familial lines of pigeons fed exogenous cholesterol.

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Patton, N M; Brown, R V; Middleton, C C

1975-01-01

Exogenous cholesterol was fed to F1 pigeons of high and low serum cholesterol differentiated lines of White Carneau and Racing Homer pigeons that had previously been developed by selection and positive assortive mating. The serum cholesterol response of the various high and low lines was dependent upon the breed and the amount of cholesterol in the diet. Racing Homer pigeons were found to be more resistant to aortic atherosclerosis and more susceptible to coronary atherosclerosis than White Carneau pigeons. Data from necropsy examinations showed significant differences in both aortic and coronary atherosclerosis between lines within the White Carneau breed, but no differences between lines of the Racing Homer breed. Mean organ weights for the 4 lines of pigeons were reported.

Nanomedicine for the prevention, treatment and imaging of atherosclerosis.

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Psarros, Costas; Lee, Regent; Margaritis, Marios; Antoniades, Charalambos

2012-09-01

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in developed countries, with an increasing prevalence due to an aging population. The pathology underpinning CVD is atherosclerosis, a chronic inflammatory state involving the arterial wall. Accumulation of low density lipoprotein (LDL) laden macrophages in the arterial wall and their subsequent transformation into foam cells lead to atherosclerotic plaque formation. Progression of atherosclerotic lesions may gradually lead to plaque related complications and clinically manifest as acute vascular syndromes including acute myocardial or cerebral ischemia. Nanotechnology offers emerging therapeutic strategies, which may have advantage overclassical treatments for atherosclerosis. In this review, we present the potential applications of nanotechnology toward prevention, identification and treatment of atherosclerosis. Copyright © 2012 Elsevier Inc. All rights reserved.

[Homocystein serum levels and lipid parameters in children with atherosclerosis risk factors].

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Sierakowska-Fijałek, Anna; Kaczmarek, Piotr; Pokoca, Lech; Smorag, Ireneusz; Wosik-Erenbek, Marzenna; Baj, Zbigniew

2007-02-01

Atherosclerosis is a disease of adult patients, however, it begins in childhood and progresses from fatty streaks to raised lesions in arteries in adolescence and young adults. Clinical manifestation of atherosclerosis in adulthood depends on the risk factors such as: lipid disorders, obesity, hypertension, smoking habits and family history of CHD. High serum homocysteine concentration is increasingly recognised as a new risk factor for atherosclerosis and other vascular diseases. Atherogenic effect of homocystein is related to cytotoxin action on the endothelial cells and their function. The aim of this study was to estimate relations between the homocysteine serum concentration and the lipid levels in children with atherosclerosis risk factors. The study was carried out on 48 children with atherosclerosis risk factors. The control group consisted of 25 healthy childrens. Total cholesterol (TC), Triglycerides (TG), HDL-C, LDL-C were determined by enzymatic method. Concentration of homocysteine was estimated by immunoenzymatic method (ELISA). Obesity, lipid disorders, and hypertension were the most frequent risk factors in the investigated children. Statistically significant higher concentration of TC, LDL-C, TG and lower HDL-C were observed in children with atherosclerosis risk factors. No significant differences in homocystein concentration were observed in the investigated groups, but homocystein concentration was significantly higher in group of children with atherosclerosis risk factors. We observed that increased number of the risk factors is followed by high homocystein concentration in the serum.

Endothelial activation, endothelial dysfunction and premature atherosclerosis in systemic autoimmune diseases

NARCIS (Netherlands)

Bijl, M

Atherosclerosis may be considered an inflammatory disease characterised by the development of atherosclerotic plaques and ischaemic cardiovascular events. Increased prevalence of cardiovascular morbidity and mortality due to (premature) atherosclerosis has been observed in patients with autoimmune

A quantitative approach of abdominal aortic atherosclerosis with x-ray computed tomography

International Nuclear Information System (INIS)

Watanabe, Hiromi; Kubota, Kazuo; Ito, Kengo; Ono, Shuichi; Matsuzawa, Taiju

1983-01-01

Currently epidemiologic studies of aortic atherosclerosis are most commonly done by the conventional roentgenological or pathological methods before and after death respectively. Pathological method is difficult and only possible after death. Roentgenological method is simple and useful before death, but its inability to evaluate atherosclerosis in a constant manner is serious drawback. A simple and quantitative method for epidemiological and clinical study of atherosclerosis has been needed. It this study, we examined the usefulness of Calcification Index (C.I.) caliculated from CT films for the evaluation of abdominal aortic atherosclerosis. We analysed 42 patients (32 males, 10 females). They recieved abdominal CT examination and died within a year. First, we got C.I. from their CT films. Then we got Surface Involved (S.I.) of atherosclerotic lesion from their autopsied abdominal aorta with pathological observation. The correlation coefficient between C.I. and S.I. was 0.83 (p<0.001). So we may use C.I. for the evaluation of abdominal aortic atherosclerosis. (author)

Hematocrit is associated with carotid atherosclerosis in men but not in women.

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Irace, Concetta; Ciamei, Monica; Crivaro, Andrea; Fiaschi, Elio; Madia, Angela; Cortese, Claudio; Gnasso, Agostino

2003-06-01

It is known that blood and plasma viscosities are associated with clinical manifestations of atherosclerosis, though evidence is not conclusive particularly in women. To verify whether hematocrit and blood and plasma viscosities are independently associated with carotid atherosclerosis and whether their measurement can improve the definition of the global coronary heart disease (CHD) risk. Eight hundred and ninety-two participants in a cardiovascular disease prevention campaign were examined with regard to conventional CHD risk factors (age, blood pressure, lipids, glucose, body mass index, waist/hip ratio, cigarette smoking and diabetes), hematocrit and blood and plasma viscosities. According to the degree of carotid atherosclerosis, investigated by echo-Doppler, participants were divided in three groups: those without atherosclerosis, those with a low degree of atherosclerosis and those with a high degree of atherosclerosis. In men, age, blood pressure, intima-media thickness (IMT), hematocrit (47.4+/-3.7%, 47.8+/-3.7%, 48.4+/-3.7%, Pviscosity (4.69+/-0.51 cP, 4.77+/-0.55 cP, 4.82+/-0.51 cP, P=0.05) increased with increasing degree of carotid atherosclerosis. In women, age, blood pressure, total cholesterol and low-density lipoprotein-cholesterol, IMT and plasma viscosity (1.42+/-0.12 cP, 1.44+/-0.11 cP, 1.46+/-0.13 cP, Pviscosity was no longer different in the three groups. In discriminant analysis, hematocrit, among the hemorheological variables investigated, was independently associated with carotid score in men (F=3.66, Pviscosities were significantly associated with carotid score in women. These findings suggest that in men, both hematocrit and blood viscosity are related to carotid atherosclerosis but hematocrit would appear to have an independent effect over and above that mediated by viscosity.

eNOS Glu298Asp polymorphism is associated with development of complicated plaques in patients from Serbia with advanced carotid atherosclerosis

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Đurić Tamara

2013-01-01

Full Text Available Nitric oxide inhibits adhesion of thrombocytes, proliferation and migration of smooth muscle cells and restricts oxidation of atherogenic low-density lipoproteins. Therefore, decreased production or activity of NO may play a role in the initiation, progression or complications of atherosclerosis. The aim of this study was to estimate the effect of Glu298Asp eNOS gene polymorphism on the individual risk for development of complicated carotid atherosclerotic plaque in patients from Serbia with advanced carotid atherosclerosis (CA who had undergone endarterectomy. The study population included 233 patients. eNOS G894T gene polymorphism was identified by PCR and RFLP methods. Multivariate logistic regression analysis showed that Asp298Asp is an independent risk factor for the presence of complicated plaques in CA patients. Patients who were homozygous for the Asp298 allele had an adjusted OR of 4.36 for the development of complicated plaques compared to those that carry the Glu298 allele. Further validation and replication studies are needed. [Projekat Ministarstva nauke Republike Srbije, br. OI175085

MicroRNA-30c Mimic Mitigates Hypercholesterolemia and Atherosclerosis in Mice.

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Irani, Sara; Pan, Xiaoyue; Peck, Bailey C E; Iqbal, Jahangir; Sethupathy, Praveen; Hussain, M Mahmood

2016-08-26

High plasma cholesterol levels are a major risk factor for atherosclerosis. Plasma cholesterol can be reduced by inhibiting lipoprotein production; however, this is associated with steatosis. Previously we showed that lentivirally mediated hepatic expression of microRNA-30c (miR-30c) reduced hyperlipidemia and atherosclerosis in mice without causing hepatosteatosis. Because viral therapy would be formidable, we examined whether a miR-30c mimic can be used to mitigate hyperlipidemia and atherosclerosis without inducing steatosis. Delivery of a miR-30c mimic to the liver diminished diet-induced hypercholesterolemia in C57BL/6J mice. Reductions in plasma cholesterol levels were significantly correlated with increases in hepatic miR-30c levels. Long term dose escalation studies showed that miR-30c mimic caused sustained reductions in plasma cholesterol with no obvious side effects. Furthermore, miR-30c mimic significantly reduced hypercholesterolemia and atherosclerosis in Apoe(-/-) mice. Mechanistic studies showed that miR-30c mimic had no effect on LDL clearance but reduced lipoprotein production by down-regulating microsomal triglyceride transfer protein expression. MiR-30c had no effect on fatty acid oxidation but reduced lipid synthesis. Additionally, whole transcriptome analysis revealed that miR-30c mimic significantly down-regulated hepatic lipid synthesis pathways. Therefore, miR-30c lowers plasma cholesterol and mitigates atherosclerosis by reducing microsomal triglyceride transfer protein expression and lipoprotein production and avoids steatosis by diminishing lipid syntheses. It mitigates atherosclerosis most likely by reducing lipoprotein production and plasma cholesterol. These findings establish that increasing hepatic miR-30c levels is a viable treatment option for reducing hypercholesterolemia and atherosclerosis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Protective Effects of Hydroxychloroquine against Accelerated Atherosclerosis in Systemic Lupus Erythematosus

Science.gov (United States)

Cauli, Alberto

2018-01-01

Cardiovascular (CV) morbidity and mortality are a challenge in management of patients with systemic lupus erythematosus (SLE). Higher risk of CV disease in SLE patients is mostly related to accelerated atherosclerosis. Nevertheless, high prevalence of traditional cardiovascular risk factors in SLE patients does not fully explain the increased CV risk. Despite the pathological bases of accelerated atherosclerosis are not fully understood, it is thought that this process is driven by the complex interplay between SLE and atherosclerosis pathogenesis. Hydroxychloroquine (HCQ) is a cornerstone in treatment of SLE patients and has been thought to exert a broad spectrum of beneficial effects on disease activity, prevention of damage accrual, and mortality. Furthermore, HCQ is thought to protect against accelerated atherosclerosis targeting toll-like receptor signaling, cytokine production, T-cell and monocyte activation, oxidative stress, and endothelial dysfunction. HCQ was also described to have beneficial effects on traditional CV risk factors, such as dyslipidemia and diabetes. In conclusion, despite lacking randomized controlled trials unambiguously proving the protection of HCQ against accelerated atherosclerosis and incidence of CV events in SLE patients, evidence analyzed in this review is in favor of its beneficial effect. PMID:29670462

Apple Polyphenols Decrease Atherosclerosis and Hepatic Steatosis in ApoE−/− Mice through the ROS/MAPK/NF-κB Pathway

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Zhe-Rong Xu

2015-08-01

Full Text Available In this study, we examined the effects of apple polyphenols (APs on hyperlipidemia, atherosclerosis, hepatic steatosis and endothelial function and investigated the potential mechanisms. ApoE−/− mice were fed a western-type diet and orally treated with APs (100 mg/kg or atorvastatin (10 mg/kg for 12 weeks. Hyperlipidemia and atherosclerosis in the aortic sinuses and, and hepatic lipidosis were measured. The treatment with APs or atorvastatin induced a remarkable reduction in the atherosclerotic lesions and hepatic steatosis and decreased the levels of low-density lipoprotein, triglyceride, CCL-2 and VCAM-1 levels in the plasma. Conversely, the APs significantly increased the plasma levels of high-density lipoprotein (HDL cholesterol and markedly up-regulated the glutathione peroxidase (GPx, catalase (CAT and superoxide dismutase (SOD levels in liver tissues. Moreover, the APs treatment modulated lipid metabolism by up-regulating the transcription of associated hepatic genes including PPARα, while down-regulating the transcription of SCAP and its downstream genes associated with lipid synthesis in the liver. Histological assessment showed that the APs treatment also reduced the macrophage infiltration in the aortic root plaque and the inflammatory cells infiltrations to the liver tissues. Moreover, we confirmed that the APs treatment greatly reduced the ox-LDL-induced endothelial dysfunction and monocyte adhesion to rat aortic endothelial cells (RAECs. Mechanistically, the APs treatment suppressed the ROS/MAPK/NF-κB signaling pathway, and consequently, reduced CCL-2, ICAM-1 and VCAM-1 expression. Our results suggest that the APs are a beneficial nutritional supplement for the attenuation of atherosclerosis.

Mid-21st century air quality at the urban scale under the influence of changed climate and emissions: case studies for Paris and Stockholm

Science.gov (United States)

Markakis, K.; Valari, M.; Engardt, M.; Lacressonnière, G.; Vautard, R.; Andersson, C.

2015-10-01

Ozone, PM10 and PM2.5 concentrations over Paris, France and Stockholm, Sweden were modeled at 4 and 1 \\unit{km} horizontal resolutions respectively for the present and 2050 periods employing decade-long simulations. We account for large-scale global climate change (RCP-4.5) and fine resolution bottom-up emission projections developed by local experts and quantify their impact on future pollutant concentrations. Moreover, we identify biases related to the implementation of regional scale emission projections over the study areas by comparing modeled pollutant concentrations between the fine and coarse scale simulations. We show that over urban areas with major regional contribution (e.g., the city of Stockholm) the bias due to coarse emission inventory may be significant and lead to policy misclassification. Our results stress the need to better understand the mechanism of bias propagation across the modeling scales in order to design more successful local-scale strategies. We find that the impact of climate change is spatially homogeneous in both regions, implying strong regional influence. The climate benefit for ozone (daily average and maximum) is up to -5 % for Paris and -2 % for Stockholm city. The joined climate benefit on PM2.5 and PM10 in Paris is between -10 and -5 % while for Stockholm we observe mixed trends up to 3 % depending on season and size class. In Stockholm, emission mitigation leads to concentration reductions up to 15 % for daily average and maximum ozone and 20 % for PM and through a sensitivity analysis we show that this response is entirely due to changes in emissions at the regional scale. On the contrary, over the city of Paris (VOC-limited photochemical regime), local mitigation of NOx emissions increases future ozone concentrations due to ozone titration inhibition. This competing trend between the respective roles of emission and climate change, results in an increase in 2050 daily average ozone by 2.5 % in Paris. Climate and not

Mid-21st century air quality at the urban scale under the influence of changed climate and emissions - case studies for Paris and Stockholm

Science.gov (United States)

Markakis, Konstantinos; Valari, Myrto; Engardt, Magnuz; Lacressonniere, Gwendoline; Vautard, Robert; Andersson, Camilla

2016-02-01

Ozone, PM10 and PM2.5 concentrations over Paris, France and Stockholm, Sweden were modelled at 4 and 1 km horizontal resolutions respectively for the present and 2050 periods employing decade-long simulations. We account for large-scale global climate change (RCP-4.5) and fine-resolution bottom-up emission projections developed by local experts and quantify their impact on future pollutant concentrations. Moreover, we identify biases related to the implementation of regional-scale emission projections by comparing modelled pollutant concentrations between the fine- and coarse-scale simulations over the study areas. We show that over urban areas with major regional contribution (e.g. the city of Stockholm) the bias related to coarse-scale projections may be significant and lead to policy misclassification. Our results stress the need to better understand the mechanism of bias propagation across the modelling scales in order to design more successful local-scale strategies. We find that the impact of climate change is spatially homogeneous in both regions, implying strong regional influence. The climate benefit for ozone (daily mean and maximum) is up to -5 % for Paris and -2 % for Stockholm city. The climate benefit on PM2.5 and PM10 in Paris is between -5 and -10 %, while for Stockholm we estimate mixed trends of up to 3 % depending on season and size class. In Stockholm, emission mitigation leads to concentration reductions up to 15 % for daily mean and maximum ozone and 20 % for PM. Through a sensitivity analysis we show that this response is entirely due to changes in emissions at the regional scale. On the contrary, over the city of Paris (VOC-limited photochemical regime), local mitigation of NOx emissions increases future ozone concentrations due to ozone titration inhibition. This competing trend between the respective roles of emission and climate change, results in an increase in 2050 daily mean ozone by 2.5 % in Paris. Climate and not emission change

The Prebiotic Inulin Aggravates Accelerated Atherosclerosis in Hypercholesterolemic APOE*3-Leiden Mice.

Science.gov (United States)

Hoving, Lisa R; de Vries, Margreet R; de Jong, Rob C M; Katiraei, Saeed; Pronk, Amanda; Quax, Paul H A; van Harmelen, Vanessa; Willems van Dijk, Ko

2018-02-03

The prebiotic inulin has proven effective at lowering inflammation and plasma lipid levels. As atherosclerosis is provoked by both inflammation and hyperlipidemia, we aimed to determine the effect of inulin supplementation on atherosclerosis development in hypercholesterolemic APOE*3-Leiden ( E3L ) mice. Male E3L mice were fed a high-cholesterol (1%) diet, supplemented with or without 10% inulin for 5 weeks. At week 3, a non-constrictive cuff was placed around the right femoral artery to induce accelerated atherosclerosis. At week 5, vascular pathology was determined by lesion thickness, vascular remodeling, and lesion composition. Throughout the study, plasma lipids were measured and in week 5, blood monocyte subtypes were determined using flow cytometry analysis. In contrast to our hypothesis, inulin exacerbated atherosclerosis development, characterized by increased lesion formation and outward vascular remodeling. The lesions showed increased number of macrophages, smooth muscle cells, and collagen content. No effects on blood monocyte composition were found. Inulin significantly increased plasma total cholesterol levels and total cholesterol exposure. In conclusion, inulin aggravated accelerated atherosclerosis development in hypercholesterolemic E3L mice, accompanied by adverse lesion composition and outward remodeling. This process was not accompanied by differences in blood monocyte composition, suggesting that the aggravated atherosclerosis development was driven by increased plasma cholesterol.

The Prebiotic Inulin Aggravates Accelerated Atherosclerosis in Hypercholesterolemic APOE*3-Leiden Mice

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Lisa R. Hoving

2018-02-01

Full Text Available The prebiotic inulin has proven effective at lowering inflammation and plasma lipid levels. As atherosclerosis is provoked by both inflammation and hyperlipidemia, we aimed to determine the effect of inulin supplementation on atherosclerosis development in hypercholesterolemic APOE*3-Leiden (E3L mice. Male E3L mice were fed a high-cholesterol (1% diet, supplemented with or without 10% inulin for 5 weeks. At week 3, a non-constrictive cuff was placed around the right femoral artery to induce accelerated atherosclerosis. At week 5, vascular pathology was determined by lesion thickness, vascular remodeling, and lesion composition. Throughout the study, plasma lipids were measured and in week 5, blood monocyte subtypes were determined using flow cytometry analysis. In contrast to our hypothesis, inulin exacerbated atherosclerosis development, characterized by increased lesion formation and outward vascular remodeling. The lesions showed increased number of macrophages, smooth muscle cells, and collagen content. No effects on blood monocyte composition were found. Inulin significantly increased plasma total cholesterol levels and total cholesterol exposure. In conclusion, inulin aggravated accelerated atherosclerosis development in hypercholesterolemic E3L mice, accompanied by adverse lesion composition and outward remodeling. This process was not accompanied by differences in blood monocyte composition, suggesting that the aggravated atherosclerosis development was driven by increased plasma cholesterol.

Proliferating macrophages prevail in atherosclerosis.

Science.gov (United States)

Randolph, Gwendalyn J

2013-09-01

Macrophages accumulate in atherosclerotic lesions during the inflammation that is part of atherosclerosis development and progression. A new study in mice indicates that the accumulation of macrophages in atherosclerotic plaques depends on local macrophage proliferation rather than the recruitment of circulating monocytes.

Effect of uremia on HDL composition, vascular inflammation, and atherosclerosis in wild-type mice

DEFF Research Database (Denmark)

Bang, Christian A; Bro, Susanne; Bartels, Emil D

2007-01-01

Wild-type mice normally do not develop atherosclerosis, unless fed cholic acid. Uremia is proinflammatory and increases atherosclerosis 6- to 10-fold in apolipoprotein E-deficient mice. This study examined the effect of uremia on lipoproteins, vascular inflammation, and atherosclerosis in wild...... in cholic acid-fed sham mice. The results suggest that moderate uremia neither induces aortic inflammation nor atherosclerosis in C57BL/6J mice despite increased LDL/HDL cholesterol ratio and altered HDL composition....

IDOL N342S Variant, Atherosclerosis Progression and Cardiovascular Disorders in the Italian General Population.

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Ashish Dhyani

Full Text Available Inducible degrader of the low density lipoprotein receptor (IDOL, is an E3 ubiquitin ligase that negatively modulates low density lipoprotein receptor (LDL-R expression. Genome-wide association studies (GWAS indicated that genetic variants in IDOL gene contributes to variation in LDL-C plasma levels and the detailed analysis of a specific locus resulted in the identification of the functional common single nucleotide polymorphism (SNP rs9370867 (c.G1025A, p.N342S associates with increased LDL-R degradation and increased LDL-C levels. These findings, however, were not confirmed in two other independent cohorts and no data about the impact of this variant on atherosclerosis progression and cardiovascular risk are available. Aim of this study was to investigate the association between a functional variant in IDOL and atherosclerosis progression in an Italian general population. 1384 subjects enrolled in the PLIC study (Progression of Lesions in the Intima of Carotid were genotyped by Q-PCR allelic discrimination and the association with anthropometric parameters, plasma lipids and the carotid intima media thickness (cIMT and the impact on cardiovascular disease (CVD incidence were investigated. The N342S variant was not associated with changes of the plasma lipid profile among GG, AG or AA carriers, including total cholesterol (249±21, 249±19 and 248±21 mg/dl respectively, LDL-C (158±25, 161±22 and 160±23 mg/dL, cIMT (0.74±0.14, 0.75±0.17 and 0.77±0.15 mm and CVD incidence. In agreement, the expression of LDLR and the uptake of LDL was similar in macrophages derived from GG and AA carriers. Taken together our findings indicate that the N342S variant does not impact plasma lipid profile and is not associated with atherosclerosis progression and CVD in the general population, suggesting that other variants in the IDOL gene might be functionally linked with cholesterol metabolism.

Innate lymphoid cells in atherosclerosis.

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Engelbertsen, Daniel; Lichtman, Andrew H

2017-12-05

The family of innate lymphoid cells (ILCs) consisting of NK cells, lymphoid tissue inducer cells and the 'helper'-like ILC subsets ILC1, ILC2 and ILC3 have been shown to have important roles in protection against microbes, regulation of inflammatory diseases and involved in allergic reactions. ILC1s produce IFN-γ upon stimulation with IL-12 and IL-18, ILC2s produce IL-5 and IL-13 responding to IL-33 and IL-25 while ILC3s produce IL-17 and IL-22 after stimulation with IL-23 or IL-1. Although few studies have directly investigated the role for ILCs in atherosclerosis, several studies have investigated transcription factors and cytokines shared by ILCs and T helper cells. In this review we summarize our current understanding of the role of ILC in atherosclerosis and discuss future directions. Copyright © 2017. Published by Elsevier B.V.

A pilot study into measurements of markers of atherosclerosis in periodontitis

NARCIS (Netherlands)

Leivadaros, E; van der Velden, U; Bizzarro, S; ten Heggeler, JMAG; Gerdes, VEA; Hoek, FJ; Nagy, TOM; Scholma, J; Bakker, SJL; Gans, ROB; ten Cate, H; Loos, BG

Background: Periodontitis may be a possible risk factor for atherosclerosis. The current pilot study explored arterial wall thickness and other variables associated with atherosclerosis in healthy subjects with and without periodontitis. Methods: Patients with moderate (N = 34) and severe

Redox balance and blood elemental levels in atherosclerosis

Energy Technology Data Exchange (ETDEWEB)

Napoleao, P. [Centro de Biologia Ambiental and Departamento de Biologia Animal, Faculdade de Ciencias de Lisboa, C2, Campo Grande, 1749-016 Lisbon (Portugal) and Laboratorio de Feixes de Ioes, Instituto Tecnologico e Nuclear, E.N. no 10, 2685-953 Sacavem (Portugal)]. E-mail: pnapoleao@itn.pt; Lopes, P.A. [Centro de Biologia Ambiental and Departamento de Biologia Animal, Faculdade de Ciencias de Lisboa, C2, Campo Grande, 1749-016 Lisbon (Portugal); Santos, M. [Centro de Quimica e Bioquimica and Departamento de Quimica e Bioquimica, Faculdade de Ciencias de Lisboa, 1749-016 Lisbon (Portugal); Steghens, J.-P. [Federation de Biochimie, Hopital Edouard Herriot, 3 Place d' Arsonval, 69437 03 Lyon (France); Viegas-Crespo, A.M. [Centro de Biologia Ambiental and Departamento de Biologia Animal, Faculdade de Ciencias de Lisboa, C2, Campo Grande, 1749-016 Lisbon (Portugal); Pinheiro, T. [Laboratorio de Feixes de Ioes, Instituto Tecnologico e Nuclear, E.N. no 10, 2685-953 Sacavem (Portugal); Centro de Fisica Nuclear, Universidade de Lisboa, Av. Prof. Egas Moniz, 1700 Lisbon (Portugal)

2006-08-15

Oxidation of lipids and proteins represents a causative event for atherogenesis, which can be opposed by antioxidant activity. Elements, such as, Fe, Cu, Zn and Se can be involved in both mechanisms. Thus, evaluation of blood elemental levels, easily detected by PIXE, and of redox parameters may be useful in assessing the risk of atherosclerosis. A group of stable patients suffering from atherosclerosis, was matched with a cohort of normo-tensive and -lipidemic volunteers. Although no major discrepancies were observed for trace elemental levels in blood, increased concentrations of K and Ca were found in atherosclerotic group. Patients presented enhance levels of antioxidant ({alpha}-tocopherol) and decreased of protein oxidation (protein carbonyls), while for the lipid oxidation marker (malondialdehyde) no variation was observed. This study contributes to a better understanding of atherosclerosis development and its relationship with blood elemental levels, and set basis for further clinical trials with pathological groups in acute phase.

Circumflex coronary artery with aberrant origin and atherosclerosis

International Nuclear Information System (INIS)

Ozcan, E.; Bozlar, U.; Celik, T.; Tasar, M.

2012-01-01

Full text: Introduction: Circumflex (Cx) coronary artery congenital anomaly is reported to be less than 1% incidence. Coronary arteries with aberrant origin are more likely to have atherosclerosis according to some published literatures. Objectives and tasks: In this study we aim to present computed tomography (CT) angiography findings of a patient, who has Cx artery with aberrant origin and atherosclerotic. Materials and methods: 57-year-old woman without any symptoms who has risk factors to atherosclerosis was referred to our clinic for coronary CT angiography. Results: In CT angiography; we detected Cx coronary artery with aberrant origin (right sinus of valsalva) and retroaortic course. Also we saw intimal irregularities and calcified plaque causing severe narrowing in the proximal segment of artery. Right coronary and left anterior descendant arteries had mild atherosclerosis. Conclusion: Coroner CT angiography, which allows multiplanar imaging with high resolution, is an effective diagnostic tool for coronary artery disease, like not only congenital anomalies but also acquired atherosclerotic disease

A pilot study into measurements of markers of atherosclerosis in periodontitis

NARCIS (Netherlands)

Leivadaros, Efstratios; van der Velden, Ubele; Bizzarro, Sergio; ten Heggeler, Johanna M. A. G.; Gerdes, Victor E. A.; Hoek, Frans J.; Nagy, Thomas O. M.; Scholma, Jose; Bakker, Stephan J. L.; Gans, Rijk O. B.; ten Cate, Hugo; Loos, Bruno G.

2005-01-01

Periodontitis may be a possible risk factor for atherosclerosis. The current pilot study explored arterial wall thickness and other variables associated with atherosclerosis in healthy subjects with and without periodontitis. Patients with moderate (N = 34) and severe periodontitis (N = 15) and

Noninvasive ultrasound molecular imaging of the effect of statins on endothelial inflammatory phenotype in early atherosclerosis.

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Elham Khanicheh

Full Text Available BACKGROUND/OBJECTIVES: Inflammatory changes on the endothelium are responsible for leukocyte recruitment to plaques in atherosclerosis. Noninvasive assessment of treatment-effects on endothelial inflammation may be of use for managing medical therapy and developing novel therapies. We hypothesized that molecular imaging of vascular cell adhesion molecule-1 (VCAM-1 with contrast enhanced ultrasound (CEU could assess treatment effects on endothelial phenotype in early atherosclerosis. METHODS: Mice with atherosclerosis produced by gene deletion of the LDL-receptor and Apobec-1-editing protein were studied. At 12 weeks of age, mice received 8 weeks of regular chow or atorvastatin-enriched chow (10 mg/kg/day. At 20 weeks, CEU molecular imaging for aortic endothelial VCAM-1 expression was performed with VCAM-1-targeted (MB(VCAM and control microbubbles (MB(Ctr. Aortic wall thickness was assessed with high frequency ultrasound. Histology, immunohistology and Western blot were used to assess plaque burden and VCAM-1 expression. RESULTS: Plaque burden was reduced on histology, and VCAM-1 was reduced on Western blot by atorvastatin, which corresponded to less endothelial expression of VCAM-1 on immunohistology. High frequency ultrasound did not detect differences in aortic wall thickness between groups. In contrast, CEU molecular imaging demonstrated selective signal enhancement for MB(VCAM in non-treated animals (MB(VCAM 2±0.3 vs MB(Ctr 0.7±0.2, p<0.01, but not in statin-treated animals (MB(VCAM 0.8±0.2 vs MB(Ctr 1.0±0.2, p = ns; p<0.01 for the effect of statin on MB(VCAM signal. CONCLUSIONS: Non-invasive CEU molecular imaging detects the effects of anti-inflammatory treatment on endothelial inflammation in early atherosclerosis. This easily accessible, low-cost technique may be useful in assessing treatment effects in preclinical research and in patients.

Recent advances in lipoprotein and atherosclerosis: A nutrigenomic approach

OpenAIRE

López, Sergio; Ortega, Almudena; Varela, Lourdes; Bermúdez, Beatriz; Muriana, Francisco JG; Abia, Rocío

2009-01-01

Atherosclerosis is a disease in which multiple factors contribute to the degeneration of the vascular wall. Many risk factors have been identified as having influence on the progression of atherosclerosis among them, the type of diet. Multifactorial interaction among lipoproteins, vascular wall cells, and inflammatory mediators has been recognised as the basis of atherogenesis. Dietary intake affects lipoprotein concentration and composition providing risk or protection at several stages of a...

Implications of alcoholic cirrhosis in atherosclerosis of autopsied patients

OpenAIRE

Silveira, Luciano Alves Matias da; Torquato, Bianca Gonçalves Silva; Oliveira, Mariana Silva; Juliano, Guilherme Ribeiro; Oliveira, Lívia Ferreira; Cavellani, Camila Lourencini; Ramalho, Luciana Santos; Espindula, Ana Paula; Teixeira, Vicente de Paula Antunes; Ferraz, Mara Lúcia Fonseca

2017-01-01

Summary Introduction: Alcoholism is a major public health problem, which has a high social cost and affects many aspects of human activity. Liver disease is one of the first consequences of alcohol abuse, and steatosis, liver cirrhosis and hepatitis may occur. Other organs are also affected with pathological changes, such as pancreatitis, cardiomyopathies, dyslipidemias and atherosclerosis. Objective: To identify the occurrence and degree of atherosclerosis in alcohol-dependent individuals ...

[¹⁸F]-fluorodeoxyglucose PET imaging of atherosclerosis

DEFF Research Database (Denmark)

Blomberg, Björn Alexander; Høilund-Carlsen, Poul Flemming

2015-01-01

[(18)F]-fluorodeoxyglucose PET ((18)FDG PET) imaging has emerged as a promising tool for assessment of atherosclerosis. By targeting atherosclerotic plaque glycolysis, a marker for plaque inflammation and hypoxia, (18)FDG PET can assess plaque vulnerability and potentially predict risk...... of atherosclerosis-related disease, such as stroke and myocardial infarction. With excellent reproducibility, (18)FDG PET can be a surrogate end point in clinical drug trials, improving trial efficiency. This article summarizes key findings in the literature, discusses limitations of (18)FDG PET imaging...

LOX-1 and Its Splice Variants: A New Challenge for Atherosclerosis and Cancer-Targeted Therapies

Science.gov (United States)

Rizzacasa, Barbara; Morini, Elena; Pucci, Sabina; Murdocca, Michela; Novelli, Giuseppe; Amati, Francesca

2017-01-01

Alternative splicing (AS) is a process in which precursor messenger RNA (pre-mRNA) splicing sites are differentially selected to diversify the protein isoform population. Changes in AS patterns have an essential role in normal development, differentiation and response to physiological stimuli. It is documented that AS can generate both “risk” and “protective” splice variants that can contribute to the pathogenesis of several diseases including atherosclerosis. The main endothelial receptor for oxidized low-density lipoprotein (ox-LDLs) is LOX-1 receptor protein encoded by the OLR1 gene. When OLR1 undergoes AS events, it generates three variants: OLR1, OLR1D4 and LOXIN. The latter lacks exon 5 and two-thirds of the functional domain. Literature data demonstrate a protective role of LOXIN in pathologies correlated with LOX-1 overexpression such as atherosclerosis and tumors. In this review, we summarize recent developments in understanding of OLR1 AS while also highlighting data warranting further investigation of this process as a novel therapeutic target. PMID:28146073

Reduction of mouse atherosclerosis by urokinase inhibition or with a limited-spectrum matrix metalloproteinase inhibitor

DEFF Research Database (Denmark)

Hu, Jie Hong; Touch, Phanith; Zhang, Jingwan

2015-01-01

-accelerated atherosclerosis) to investigate whether systemic inhibition of proteolytic activity of uPA or a subset of MMPs can reduce protease-induced atherosclerosis and aortic dilation. METHODS AND RESULTS: SR-uPA mice were fed a high-fat diet for 10 weeks and treated either with an antibody inhibiting mouse uPA (mU1...... surface lesion coverage. Several lines of evidence identified MMP-13 as a mediator of uPA-induced aortic MMP activity. CONCLUSIONS: Pharmacological inhibition of either uPA or selected MMPs decreased atherosclerosis in SR-uPA mice. uPA inhibition decreased aortic dilation. Differential effects of both...... agents on aortic root vs. distal aortic atherosclerosis suggest prevention of atherosclerosis progression vs. initiation. Systemic inhibition of uPA or a subset of MMPs shows promise for treating atherosclerosis....

Management of radiation-induced accelerated carotid atherosclerosis

International Nuclear Information System (INIS)

Loftus, C.M.; Biller, J.; Hart, M.N.; Cornell, S.H.; Hiratzka, L.F.

1987-01-01

Patients with long survival following cervical irradiation are at risk for accelerated carotid atherosclerosis. The neurologic presentation in these patients mimics naturally occurring atheromatous disease, but patients often present at younger ages and with less concurrent coronary or systemic vascular disease. Hypercholesterolemia also contributes to this accelerated arteriosclerosis. Angiographic findings in this disorder include disproportionate involvement of the distal common carotid artery and unusually long carotid lesions. Pathologic findings include destruction of the internal elastic lamina and replacement of the normal intima and media with fibrous tissue. This article describes two surgical patients with radiation-induced accelerated carotid atherosclerosis who typify the presentation and characteristics of this disease

Life and Death in the City: Demography and Living Standards during Stockholm's Industrialization

DEFF Research Database (Denmark)

Molitoris, Joseph John

2015-01-01

’s intergenerational social mobility, and infant and child mortality during Stockholm’s industrialization and fertility transition. The results of this work challenge many existing explanations of the fertility decline and reveal how, despite overall improvements in living standards, elite socioeconomic groups were......This dissertation uses longitudinal micro-data from Stockholm between 1878 and 1926 to study the causes and consequences of the fertility transition and to examine the development of living standards inequality during industrialization. Although both processes have received much interest from...... able to continually leverage their superior resources to maintain significantly lower levels of infant and child mortality....

Ageing induced vascular smooth muscle cell senescence in atherosclerosis.

Science.gov (United States)

Uryga, Anna K; Bennett, Martin R

2016-04-15

Atherosclerosis is a disease of ageing in that its incidence and prevalence increase with age. However, atherosclerosis is also associated with biological ageing, manifest by a number of typical hallmarks of ageing in the atherosclerotic plaque. Thus, accelerated biological ageing may be superimposed on the effects of chronological ageing in atherosclerosis. Tissue ageing is seen in all cells that comprise the plaque, but particularly in vascular smooth muscle cells (VSMCs). Hallmarks of ageing include evidence of cell senescence, DNA damage (including telomere attrition), mitochondrial dysfunction, a pro-inflammatory secretory phenotype, defects in proteostasis, epigenetic changes, deregulated nutrient sensing, and exhaustion of progenitor cells. In this model, initial damage to DNA (genomic, telomeric, mitochondrial and epigenetic changes) results in a number of cellular responses (cellular senescence, deregulated nutrient sensing and defects in proteostasis). Ultimately, ongoing damage and attempts at repair by continued proliferation overwhelm reparative capacity, causing loss of specialised cell functions, cell death and inflammation. This review summarises the evidence for accelerated biological ageing in atherosclerosis, the functional consequences of cell ageing on cells comprising the plaque, and the causal role that VSMC senescence plays in atherogenesis. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Lack of association between a functional variant of the BRCA-1 related associated protein (BRAP) gene and ischemic stroke

OpenAIRE

Liao, Yi-Chu; Lin, Hsiu-Fen; Guo, Yuh-Cherng; Chen, Chung-Hung; Huang, Zhi-Zhang; Juo, Suh-Hang Hank; Lin, Ruey-Tay

2013-01-01

Abstract Background Atherosclerosis shares common pathogenic features with myocardial infarction (MI) and ischemic stroke. BRCA-1 associated protein (BRAP), a newly identified risk gene for MI, aggravates the inflammatory response in atherosclerosis. The aim of this study was to test the association between the BRAP gene and stroke in a Taiwanese population. Methods A total of 1,074 stroke patients and 1,936 controls were genotyped for the functional SNP rs11066001. In our previous studies, t...

Solubility and Potential Mobility of Heavy Metals in Two Contaminated Urban Soils from Stockholm, Sweden

International Nuclear Information System (INIS)

Oborn, Ingrid; Linde, Mats

2001-01-01

The solubility and potential mobility of heavy metals (Cd, Cu,Hg, Pb and Zn) in two urban soils were studied by sequential and leaching extractions (rainwater). Compared to rural (arable) soils on similar parent material, the urban soils were highly contaminated with Hg and Pb and to a lesser extent also with Cd,Cu and Zn. Metal concentrations in rainwater leachates were related to sequential extractions and metal levels reported from Stockholm groundwater. Cadmium and Zn in the soils were mainly recovered in easily extractable fractions, whereas Cu and Pb were complex bound. Concentrations of Pb in the residual fraction were between two- and eightfold those in arable soils, indicating that the sequential extraction scheme did not reflect the solid phases affected by anthropogenic inputs. Cadmium and Zn conc. in the rainwater leachates were within the range detected in Stockholm groundwater, while Cu and Pb conc. were higher, which suggests that Cu and Pb released from the surface soil were immobilised in deeper soil layers. In a soil highly contaminated with Hg, the Hg conc. in the leachate was above the median concentration, but still 50 times lower than the max concentration found in groundwater, indicating the possibility of other sources. In conclusion, it proved difficult to quantitatively predict the mobility of metals in soils by sequential extractions

Prevalence of Autism in Children of Somali Origin Living in Stockholm: Brief Report of an At-Risk Population

Science.gov (United States)

Barnevik-Olsson, Martina; Gillberg, Christopher; Fernell, Elisabeth

2010-01-01

This work was a follow-up study (birth years 1999-2003) of the prevalence of autism in children of Somali background living in the county of Stockholm, Sweden. In a previous study (birth years 1988-98), the prevalence of autism associated with learning disability was found to be three to four times higher among Somali children compared with other…

Recommendations from the ESO-Karolinska Stroke Update Conference, Stockholm 13–15 November 2016

DEFF Research Database (Denmark)

2017-01-01

-Karolinska Stroke Update Meeting was held in Stockholm on 13–15 November 2016. There were 10 scientific sessions discussed in the meeting and each session produced a consensus statement (Full version with background, issues, conclusions and references are published as web-material and at http...... and statistical reviews (at least one randomised controlled trial plus one statistical review). Grade B Evidence: Support from randomised controlled trials and statistical reviews (one randomised controlled trial or one statistical review). Grade C Evidence: No reasonable support from randomised controlled trials...

Planning the Green Walkable City: Conceptualizing Values and Conflicts for Urban Green Space Strategies in Stockholm

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Hélène Littke

2015-08-01

Full Text Available Urban green spaces are essential elements of cities, contributing to the quality of life in numerous ways. However, densification strategies create a complex relationship between urban development and the quality, as well as the quantity, of urban green space. This paper examines the Green Walkable City Programme in Stockholm, a document developed to supplement the comprehensive plan as a strategic backbone for green urban planning. Based on interviews and content analysis, this paper identifies and discusses concerns raised in the development of the planning programme, and addresses the importance of urban green space for citizens’ well-being. The new comprehensive plan has introduced a shift in the attitude towards the urban green space in Stockholm. The need for urban growth is used to justify development of green fields, and a focus on the quality, rather than the quantity, of urban green space is promoted. Despite this progress, the public requests definitions for this quality approach and fears that nature within the city will be “parkified”. Therefore, this paper offers a critical reflection on the role of the Green Walkable City Programme, its situation within the context of Swedish green urban planning, and various areas of concern that have been highlighted.

A patient with Werner syndrome and adiponectin gene mutation.

Science.gov (United States)

Hashimoto, Naotake; Hatanaka, Sachiko; Yokote, Koutaro; Kurosawa, Hiroko; Yoshida, Tomohiko; Iwai, Rie; Takahashi, Hidenori; Yoshida, Katsuya; Horie, Atsuya; Sakurai, Kenichi; Yagui, Kazuo; Saito, Yasushi; Yoshida, Shouji

2007-01-01

Werner syndrome is a premature aging disease characterized by genomic instability and increased cancer risk. Here, we report a 45-year-old diabetic man as the first Werner syndrome patient found to have an adiponectin gene mutation. Showing graying and loss of hair, skin atrophy, and juvenile cataract, he was diagnosed with Werner syndrome type 4 by molecular analysis. His serum adiponectin concentration was low. In the globular domain of the adiponectin gene, I164T in exon 3 was detected. When we examined effects of pioglitazone (15 mg/day) on serum adiponectin multimer and monomer concentrations using selective assays, the patient's relative percentage increased in adiponectin concentration was almost same as that in the 18 diabetic patients without an adiponectin mutation, but the absolute adiponectin concentration was half of those seen in diabetic patients treated with the same pioglitazone dose who had no adiponectin mutation. The response suggested that pioglitazone treatment might help to prevent future Werner syndrome-related acceleration of atherosclerosis. Present and further clinical relevant to atherosclerosis in this patient should be imformative concerning the pathogenesis and treatment of atherosclerosis in the presence of hypoadiponectinemia and insulin resistance.

Oxyradical Stress, Endocannabinoids, and Atherosclerosis

Directory of Open Access Journals (Sweden)

Anberitha T. Matthews

2015-12-01

Full Text Available Atherosclerosis is responsible for most cardiovascular disease (CVD and is caused by several factors including hypertension, hypercholesterolemia, and chronic inflammation. Oxidants and electrophiles have roles in the pathophysiology of atherosclerosis and the concentrations of these reactive molecules are an important factor in disease initiation and progression. Overactive NADPH oxidase (Nox produces excess superoxide resulting in oxidized macromolecules, which is an important factor in atherogenesis. Although superoxide and reactive oxygen species (ROS have obvious toxic properties, they also have fundamental roles in signaling pathways that enable cells to adapt to stress. In addition to inflammation and ROS, the endocannabinoid system (eCB is also important in atherogenesis. Linkages have been postulated between the eCB system, Nox, oxidative stress, and atherosclerosis. For instance, CB2 receptor-evoked signaling has been shown to upregulate anti-inflammatory and anti-oxidative pathways, whereas CB1 signaling appears to induce opposite effects. The second messenger lipid molecule diacylglycerol is implicated in the regulation of Nox activity and diacylglycerol lipase β (DAGLβ is a key biosynthetic enzyme in the biosynthesis eCB ligand 2-arachidonylglycerol (2-AG. Furthermore, Nrf2 is a vital transcription factor that protects against the cytotoxic effects of both oxidant and electrophile stress. This review will highlight the role of reactive oxygen species (ROS in intracellular signaling and the impact of deregulated ROS-mediated signaling in atherogenesis. In addition, there is also emerging knowledge that the eCB system has an important role in atherogenesis. We will attempt to integrate oxidative stress and the eCB system into a conceptual framework that provides insights into this pathology.

The emergence of a post-industrial music economy? : Music and ICT synergies in Stockholm, Sweden.

OpenAIRE

Power, Dominic; Jansson, Johan

2004-01-01

Research into the music industry has for a long time been almost exclusively dominated by a focus on the production of albums and songs. In recent years, however, cities such as Stockholm have seen the growth of a profitable and varied music services industry producing everything from remixes to music marketing strategies. Standing at the forefront of this growth industry are a large number of firms attempting to combine in innovative ways music and ICT. This can take a variety of forms, for ...

RENAL INVOLVEMENT IN SUBJECTS WITH PERIPHERAL ATHEROSCLEROSIS

International Nuclear Information System (INIS)

FAWZY, A.; IBRAHIM, S.

2008-01-01

Ischemic nephropathy is an important cause of renal failure.Sub-clinical renal function abnormalities may exist in patients with extra renal atherosclerosis and may precede the onset of overt ischemic nephropathy. To assess the impact of extrarenal atherosclerosis on the kidney, the study evaluated renal function in 50 subjects with differing degrees of peripheral atherosclerosis without manifest clinical or laboratory signs of ischemic nephropathy and renovascular hypertension.All laboratory testing including total LDL and HDL-cholesterol, triglycerides, ultrasonography with Doppler analysis for the localization of peripheral vascular disease (carotid and lower limb arteries), and non-invasive evaluation of renal function by radionuclide studies of renal plasma flow (MAG3 clearance) and glomerular filtration (DTPA clearance) were determined as well as smoking habit was recorded. By combining sonographic data on arterial tree stenosis (ATS), the subjects were grouped according to the atherosclerotic vascular damage (ATS involvement). The results showed no change in plasma creatinine while DTPA clearance was increased from 91.58±26.53 to 93.47±24.82 ml/min/1.73 m. MAG3 clearance was progressively declined with the severity of vascular damage from 244.86 ± 60.60 to 173.59±58.74 ml/min/1.73 m.Stepwise, multiple regression analysis indicated that MAG3 clearance was best explained by ATS involvement (standardized B coefficient -0.40; P< 0.001), smoking habit (-0.34;P=0.004) and serum LDL-cholesterol (-0.24; P<0.035).It could be concluded that the renal hemodynamic profile in atherosclerotic patients might constitute functional evidence of the silent phase of ischemic renal disease. The findings suggest that renal function should be carefully assessed in patients with extrarenal atherosclerosis, particularly in those with classic cardiovascular risk factors

Valsartan Promoting Atherosclerotic Plaque Stabilization by Upregulating Renalase: A Potential-Related Gene of Atherosclerosis.

Science.gov (United States)

Zhou, Mingxue; Ma, Chao; Liu, Weihong; Liu, Hongxu; Wang, Ning; Kang, Qunfu; Li, Ping

2015-09-01

Renalase is a protein that can regulate sympathetic nerve activity by metabolizing catecholamines, while redundant catecholamines are thought to contribute to atherosclerosis (As). Catecholamine release can be facilitated by angiotensin (Ang) II by binding to Ang II type 1 (AT1) receptors. Valsartan, a special AT1 antagonist, can dilate blood vessels and reduce blood pressure, but it remained unclear whether valsartan can promote the stability of atherosclerotic plaque by affecting renalase. This study examined the tissue distribution of renalase in ApoE(-/-) mice fed with a high-fat diet and the effect of valsartan on expression of renalase. ApoE(-/-) mice were fed with a high-fat diet for 13 or 26 weeks. As a control, 10 C57BL mice were fed with a standard chow diet. After 13 weeks on the high-fat diet, the ApoE(-/-) mice were randomized (10 mice/group) and treated with valsartan, simvastatin, or distilled water (control group) for an additional 13 weeks accompanied by a high-fat diet. Knockout of ApoE caused a dramatic increase in expression of renalase in mice adipose tissue. With the disturbance of lipid metabolism induced by a high-fat diet, renalase expression decreased in the liver. Renalase can be expressed in smooth muscle cells and M2 macrophages in atherosclerotic plaque, and its expression gradually decreases in the fibrous cap during the transition from stable to vulnerable atherosclerotic plaque. Valsartan, an AT1 receptor antagonist, promotes the stabilization of atherosclerotic plaque by increasing the levels of renalase in serum and the expression of renalase in the fibrous cap of atherosclerotic plaque. It also reduces triglyceride levels in serum and increases the expression of renalase in the liver. Renalase may be a potential-related gene of lipid metabolism and As, and it may be the possible molecular target of valsartan to help stabilize atherosclerotic plaque. © The Author(s) 2015.

Associations between vitamin D status and atherosclerosis among Inuit in Greenland

DEFF Research Database (Denmark)

Gjødesen, Camilla U; Jørgensen, Marit E; Bjerregaard, Peter

2018-01-01

BACKGROUND AND AIMS: Low levels of vitamin D are suspected to be a risk factor for cardiovascular disease and atherosclerosis. The aim of this study was to assess the prevalence of subclinical atherosclerosis among Inuit in Greenland, and to evaluate the association with vitamin D status. We hypo...

Visualization of atherosclerosis as detected by coronary artery calcium and carotid intima-media thickness reveals significant atherosclerosis in a cross-sectional study of psoriasis patients in a tertiary care center.

Science.gov (United States)

Santilli, S; Kast, D R; Grozdev, I; Cao, L; Feig, R L; Golden, J B; Debanne, S M; Gilkeson, R C; Orringer, C E; McCormick, T S; Ward, N L; Cooper, K D; Korman, N J

2016-07-22

Psoriasis is a chronic inflammatory disease of the skin and joints that may also have systemic inflammatory effects, including the development of cardiovascular disease (CVD). Multiple epidemiologic studies have demonstrated increased rates of CVD in psoriasis patients, although a causal link has not been established. A growing body of evidence suggests that sub-clinical systemic inflammation may develop in psoriasis patients, even from a young age. We aimed to evaluate the prevalence of atherosclerosis and identify specific clinical risk factors associated with early vascular inflammation. We conducted a cross-sectional study of a tertiary care cohort of psoriasis patients using coronary artery calcium (CAC) score and carotid intima-media thickness (CIMT) to detect atherosclerosis, along with high sensitivity C-reactive protein (hsCRP) to measure inflammation. Psoriasis patients and controls were recruited from our tertiary care dermatology clinic. Presence of atherosclerosis was defined using validated numeric values within CAC and CIMT imaging. Descriptive data comparing groups was analyzed using Welch's t test and Pearson Chi square tests. Logistic regression was used to analyze clinical factors associated with atherosclerosis, and linear regression to evaluate the relationship between psoriasis and hsCRP. 296 patients were enrolled, with 283 (207 psoriatic and 76 controls) having all data for the hsCRP and atherosclerosis analysis. Atherosclerosis was found in 67.6 % of psoriasis subjects versus 52.6 % of controls; Psoriasis patients were found to have a 2.67-fold higher odds of having atherosclerosis compared to controls [95 % CI (1.2, 5.92); p = 0.016], after adjusting for age, gender, race, BMI, smoking, HDL and hsCRP. In addition, a non-significant trend was found between HsCRP and psoriasis severity, as measured by PASI, PGA, or BSA, again after adjusting for confounders. A tertiary care cohort of psoriasis patients have a high prevalence of early

Atherosclerosis and Nanotechnology: Diagnostic and Therapeutic Applications.

Science.gov (United States)

Kratz, Jeremy D; Chaddha, Ashish; Bhattacharjee, Somnath; Goonewardena, Sascha N

2016-02-01

Over the past several decades, tremendous advances have been made in the understanding, diagnosis, and treatment of coronary artery disease (CAD). However, with shifting demographics and evolving risk factors we now face new challenges that must be met in order to further advance are management of patients with CAD. In parallel with advances in our mechanistic appreciation of CAD and atherosclerosis, nanotechnology approaches have greatly expanded, offering the potential for significant improvements in our diagnostic and therapeutic management of CAD. To realize this potential we must go beyond to recognize new frontiers including knowledge gaps between understanding atherosclerosis to the translation of targeted molecular tools. This review highlights nanotechnology applications for imaging and therapeutic advancements in CAD.

The population-based Barcelona-Asymptomatic Intracranial Atherosclerosis Study (ASIA: rationale and design

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Pera Guillem

2011-02-01

Full Text Available Abstract Background Large-artery intracranial atherosclerosis may be the most frequent cause of ischemic stroke worldwide. Traditional approaches have attempted to target the disease when it is already symptomatic. However, early detection of intracranial atherosclerosis may allow therapeutic intervention while the disease is still asymptomatic. The prevalence and natural history of asymptomatic intracranial atherosclerosis in Caucasians remain unclear. The aims of the Barcelona-ASymptomatic Intracranial Atherosclerosis (ASIA study are (1 to determine the prevalence of ASIA in a moderate-high vascular risk population, (2 to study its prognostic impact on the risk of suffering future major ischemic events, and (3 to identify predictors of the development, progression and clinical expression of this condition. Methods/Design Cross-over and cohort, population-based study. A randomly selected representative sample of 1,503 subjects with a mild-moderate-high vascular risk (as defined by a REGICOR score ≥ 5% and with neither a history of cerebrovascular nor ischemic heart disease will be studied. At baseline, all individuals will undergo extracranial and transcranial Color-Coded Duplex (TCCD ultrasound examinations to detect presence and severity of extra and intracranial atherosclerosis. Intracranial stenoses will be assessed by magnetic resonance angiography (MRA. Clinical and demographic variables will be recorded and blood samples will be drawn to investigate clinical, biological and genetic factors associated with the presence of ASIA. A long-term clinical and sonographic follow-up will be conducted thereafter to identify predictors of disease progression and of incident vascular events. Discussion The Barcelona-ASIA is a population-based study aiming to evaluate the prevalence and clinical importance of asymptomatic intracranial large-artery atherosclerosis in Caucasians. The ASIA project may provide a unique scientific resource to better

The population-based Barcelona-Asymptomatic Intracranial Atherosclerosis Study (ASIA): rationale and design.

Science.gov (United States)

López-Cancio, Elena; Dorado, Laura; Millán, Mónica; Reverté, Silvia; Suñol, Anna; Massuet, Anna; Mataró, María; Galán, Amparo; Alzamora, Maite; Pera, Guillem; Torán, Pere; Dávalos, Antoni; Arenillas, Juan F

2011-02-17

Large-artery intracranial atherosclerosis may be the most frequent cause of ischemic stroke worldwide. Traditional approaches have attempted to target the disease when it is already symptomatic. However, early detection of intracranial atherosclerosis may allow therapeutic intervention while the disease is still asymptomatic. The prevalence and natural history of asymptomatic intracranial atherosclerosis in Caucasians remain unclear. The aims of the Barcelona-ASymptomatic Intracranial Atherosclerosis (ASIA) study are (1) to determine the prevalence of ASIA in a moderate-high vascular risk population, (2) to study its prognostic impact on the risk of suffering future major ischemic events, and (3) to identify predictors of the development, progression and clinical expression of this condition. Cross-over and cohort, population-based study. A randomly selected representative sample of 1,503 subjects with a mild-moderate-high vascular risk (as defined by a REGICOR score ≥ 5%) and with neither a history of cerebrovascular nor ischemic heart disease will be studied. At baseline, all individuals will undergo extracranial and transcranial Color-Coded Duplex (TCCD) ultrasound examinations to detect presence and severity of extra and intracranial atherosclerosis. Intracranial stenoses will be assessed by magnetic resonance angiography (MRA). Clinical and demographic variables will be recorded and blood samples will be drawn to investigate clinical, biological and genetic factors associated with the presence of ASIA. A long-term clinical and sonographic follow-up will be conducted thereafter to identify predictors of disease progression and of incident vascular events. The Barcelona-ASIA is a population-based study aiming to evaluate the prevalence and clinical importance of asymptomatic intracranial large-artery atherosclerosis in Caucasians. The ASIA project may provide a unique scientific resource to better understand the dynamics of intracranial atherosclerosis from

Liraglutide Reduces Both Atherosclerosis and Kidney Inflammation in Moderately Uremic LDLr-/- Mice

DEFF Research Database (Denmark)

Bisgaard, Line S; Bosteen, Markus H; Fink, Lisbeth N

2016-01-01

Chronic kidney disease (CKD) leads to uremia. CKD is characterized by a gradual increase in kidney fibrosis and loss of kidney function, which is associated with a progressive increase in risk of atherosclerosis and cardiovascular death. To prevent progression of both kidney fibrosis and atherosc......Chronic kidney disease (CKD) leads to uremia. CKD is characterized by a gradual increase in kidney fibrosis and loss of kidney function, which is associated with a progressive increase in risk of atherosclerosis and cardiovascular death. To prevent progression of both kidney fibrosis...... aim was to examine effects of liraglutide on kidney fibrosis and atherosclerosis in a mouse model of moderate uremia (5/6 nephrectomy (NX)). Uremic (n = 29) and sham-operated (n = 14) atherosclerosis-prone low density lipoprotein receptor knockout mice were treated with liraglutide (1000 μg/kg, s.......c. once daily) or vehicle for 13 weeks. As expected, uremia increased aortic atherosclerosis. In the remnant kidneys from NX mice, flow cytometry revealed an increase in the number of monocyte-like cells (CD68+F4/80-), CD4+, and CD8+ T-cells, suggesting that moderate uremia induced kidney inflammation...

Incretin hormones as immunomodulators of atherosclerosis

Directory of Open Access Journals (Sweden)

Nuria eAlonso

2012-09-01

Full Text Available Atherosclerosis results from endothelial cell dysfunction and inflammatory processes affecting both macro-and microvasculature which are involved in vascular diabetic complications. Glucagon-like peptide 1 (GLP-1 is an incretin hormone responsible for amplification of insulin secretion when nutrients are given orally as opposed to intravenously and it retains its insulinotropic activity in patients with type 2 diabetes mellitus (T2D. GLP-1 based therapies, such as GLP-1 receptor (R agonists and inhibitors of dipeptidyl peptidase 4 (DPP-4, an enzyme that degrades endogenous GLP-1 are routinely used to treat patients with T2D. Recent experimental model studies have established that GLP-1R mRNA is widely expressed in several immune cells. Moreover, its activation contributes to the regulation of both thymocyte and peripheral T cells proliferation and is involved in the maintenance of peripheral regulatory T cells. GLP-1 R is also expressed in endothelial and smooth muscle cells. The effect of incretin hormones on atherosclerogenesis have recently been studied in animal models of apolipoprotein E-deficient mice (apo E-/-. These studies have demonstrated that treatment with incretin hormones or related compounds suppresses the progression of atherosclerosis and macrophage infiltration in the arterial wall as well as a marked anti-oxidative and anti-inflammatory effect on endothelial cells. This effect may have a major impact on the attenuation of atherosclerosis and may help in the design of new therapies for cardiovascular disease in patients with type 2 diabetes.

Overview of Atherosclerosis and Chemical Stressors

Science.gov (United States)

Dr. Cascio’s presentation at the workshop titled, “titled “Understanding the Combined Effects of Environmental Chemical and Non-Chemical Stressors: Atherosclerosis as a Model” will highlight atherosclerosis’s rapidly growing role as a cause of increa...

[Jan Kusberg, Kleine Geschichte St. Petersburgs. (Regensburg, 2009) ; Ingrid Bohn. Kleine Geschichte Stockholms. (Regensburg, 2008) ; Konrad Dittrich. Kleine Lübecker Stadtgeschichte. (Regensburg, 2007)] / Dennis Hortmuth

Index Scriptorium Estoniae

Hormuth, Dennis

2011-01-01

Arvustus: Jan Kusberg, Kleine Geschichte St. Petersburgs. (Regensburg, 2009) ; Ingrid Bohn. Kleine Geschichte Stockholms. (Regensburg, 2008) ; Konrad Dittrich. Kleine Lübecker Stadtgeschichte. (Regensburg, 2007)

Atherosclerosis in epilepsy: its causes and implications.

Science.gov (United States)

Hamed, Sherifa A

2014-12-01

Evidence from epidemiological, longitudinal, prospective, double-blinded clinical trials as well as case reports documents age-accelerated atherosclerosis with increased carotid artery intima media thickness (CA-IMT) in patients with epilepsy. These findings raise concern regarding their implications for age-accelerated cognitive and behavioral changes in midlife and risk of later age-related cognitive disorders including neurodegenerative processes such as Alzheimer's disease (AD). Chronic epilepsy, cerebral atherosclerosis, and age-related cognitive disorders including AD share many clinical manifestations (e.g. characteristic cognitive deficits), risk factors, and structural and pathological brain abnormalities. These shared risk factors include increased CA-IMT, hyperhomocysteinemia (HHcy), lipid abnormalities, weight gain and obesity, insulin resistance (IR), and high levels of inflammatory and oxidative stresses. The resulting brain structural and pathological abnormalities include decreased volume of the hippocampus, increased cortical thinning of the frontal lobe, ventricular expansion and increased white matter ischemic disease, total brain atrophy, and β-amyloid protein deposition in the brain. The knowledge that age-accelerated atherosclerosis may contribute to age-accelerated cognitive and behavioral abnormalities and structural brain pathologies in patients with chronic epilepsy represents an important research path to pursue future clinical and management considerations. Copyright © 2014 Elsevier Inc. All rights reserved.

The Humanistic Medicine program at the Karolinska Institute, Stockholm, Sweden.

Science.gov (United States)

Ahlzén, Rolf; Stolt, Carl-Magnus

2003-10-01

In 1998, the Humanistic Medicine program was established at the Karolinska Institute, Stockholm, Sweden. A fundamental element of the program is to promote medical humanities within clinical practice. The program's design focuses on three interconnected areas of study, the history of medicine, philosophy of medical science and practice, and aspects of the clinical encounter. The program offers undergraduate and postgraduate studies. The program's humanities content is bolstered in the medical curriculum by The Doctor School, a line of teaching medical students follow through their first four semesters. From this parallel series of lectures and seminars, students are exposed to further humanities and medical training. Students also have the option to select from humanities courses for their 17 eligible weeks of electives. It is hoped that the Karolinska Institute will continue to develop the humanities content of its curriculum, intertwining scientific exploration and humanistic understanding.

The Multifaceted Uses and Therapeutic Advantages of Nanoparticles for Atherosclerosis Research.

Science.gov (United States)

DiStasio, Nicholas; Lehoux, Stephanie; Khademhosseini, Ali; Tabrizian, Maryam

2018-05-08

Nanoparticles are uniquely suited for the study and development of potential therapies against atherosclerosis by virtue of their size, fine-tunable properties, and ability to incorporate therapies and/or imaging modalities. Furthermore, nanoparticles can be specifically targeted to the atherosclerotic plaque, evading off-target effects and/or associated cytotoxicity. There has been a wealth of knowledge available concerning the use of nanotechnologies in cardiovascular disease and atherosclerosis, in particular in animal models, but with a major focus on imaging agents. In fact, roughly 60% of articles from an initial search for this review included examples of imaging applications of nanoparticles. Thus, this review focuses on experimental therapy interventions applied to and observed in animal models. Particular emphasis is placed on how nanoparticle materials and properties allow researchers to learn a great deal about atherosclerosis. The objective of this review was to provide an update for nanoparticle use in imaging and drug delivery studies and to illustrate how nanoparticles can be used for sensing and modelling, for studying fundamental biological mechanisms, and for the delivery of biotherapeutics such as proteins, peptides, nucleic acids, and even cells all with the goal of attenuating atherosclerosis. Furthermore, the various atherosclerosis processes targeted mainly for imaging studies have been summarized in the hopes of inspiring new and exciting targeted therapeutic and/or imaging strategies.

Biological and chemical characterization of harbour sediments from the Stockholm area

Energy Technology Data Exchange (ETDEWEB)

Eklund, Britta; Elfstroem, Maria; Bengtsson, Bengt-Erik; Breitholtz, Magnus [Dept. of Applied Environmental Science (ITM), Stockholm Univ. (Sweden); Gallego, Irene [Granada Univ. (Spain)

2010-01-15

Purpose: The main objective of the current study was to assess the impact of pleasure boat activities on harbour sediment quality in the Stockholm area. Sediment contamination is a growing ecological issue, and there is consequently a need to use sediment bioassays in combination with chemical analysis to determine the impact on the ecosystem. To generate sediment toxicity data relevant for the Baltic Sea, a secondary objective was to further develop and evaluate two well-established bioassays for saltwater, with the macroalga Ceramium tenuicorne and the crustacean Nitocra spinipes, to be useful also for toxicity testing of whole sediment. A major concern has been to minimize any manipulation of the sediments. A third objective was to assess whether a simple leaching procedure could be used to simulate sediment toxicity by comparing results from whole sediment and leachate tests. Materials and methods: Surface sediments (0-2 cm) from five different types of pleasure boat harbours were collected. Chemical measurements of boat related compounds, i.e. tin organic substances (tributyltin (TBT), dibutyl tin, and monobutyl tin), polyaromatic hydrocarbons (PAHs), copper, zinc, lead, tin and irgarol were conducted. The sediments were tested for toxic effects using the established Microtox {sup registered} test as well as the developed sediment tests with C. tenuicorne and N. spinipes. The endpoints are growth inhibition for the algal test and for the crustacean test mortality of larvae and rate of development expressed as the ratio between nauplia and copepodites. Two different procedures have been compared with both organisms, i.e. exposure to whole sediment and to leachate. The duration of both tests is around 1 week. Results and discussion: All harbour locations were more or less heavily contaminated with remnants from use of antifouling paints. The sediment in a smaller marina (ca. 250 boats) contained the highest levels of TBT (max 1,400 {mu}g/kg dry weight (dw

Models and Analysis of Atherosclerosis, Restenosis, and Aneurysm Formation in the Mouse

NARCIS (Netherlands)

de Waard, Vivian; Gijbels, Marion J. J.; Lutgens, Esther; de Winther, Menno P. J.; de Vries, Carlie J. M.

2012-01-01

Atherosclerosis is considered a chronic inflammatory condition of the vessel wall and involves a high chronic concentration of low-density lipoprotein (LDL) in blood. In humans, restenosis develops after intravascular interventions such as angioplasty and stent placement to treat atherosclerosis,

Ginseng Berry Extract Prevents Atherogenesis via Anti-Inflammatory Action by Upregulating Phase II Gene Expression

Directory of Open Access Journals (Sweden)

Chun-Ki Kim

2012-01-01

Full Text Available Ginseng berry possesses higher ginsenoside content than its root, which has been traditionally used in herbal medicine for many human diseases, including atherosclerosis. We here examined the antiatherogenic effects of the Korean ginseng berry extract (KGBE and investigated its underlying mechanism of action in vitro and in vivo. Administration of KGBE decreased atherosclerotic lesions, which was inversely correlated with the expression levels of phase II genes to include heme oxygenase-1 (HO-1 and glutamine-cysteine ligase (GCL. Furthermore, KGBE administration suppressed NF-κB-mediated expression of atherogenic inflammatory genes (TNF-α, IL-1β, iNOS, COX-2, ICAM-1, and VCAM-1, without altering serum cholesterol levels, in ApoE-/- mice fed a high fat-diet. Treatment with KGBE increased phase II gene expression and suppressed lipopolysaccharide-induced reactive oxygen species production, NF-κB activation, and inflammatory gene expression in primary macrophages. Importantly, these cellular events were blocked by selective inhibitors of HO-1 and GCL. In addition, these inhibitors reversed the suppressive effect of KGBE on TNF-α-mediated induction of ICAM-1 and VCAM-1, resulting in decreased interaction between endothelial cells and monocytes. These results suggest that KGBE ameliorates atherosclerosis by inhibiting NF-κB-mediated expression of atherogenic genes via upregulation of phase II enzymes and thus has therapeutic or preventive potential for atherosclerosis.

Endogenous hydrogen sulfide is involved in the pathogenesis of atherosclerosis

International Nuclear Information System (INIS)

Qiao, Wang; Chaoshu, Tang; Hongfang, Jin; Junbao, Du

2010-01-01

Atherosclerosis is a chronic, complex, and progressive pathological process in large and medium sized arteries. The exact mechanism of this process remains unclear. Hydrogen sulfide (H 2 S), a novel gasotransmitter, was confirmed as playing a major role in the pathogenesis of many cardiovascular diseases. It plays a role in vascular smooth muscle cell (VSMC) proliferation and apoptosis, participates in the progress of hyperhomocysteinemia (HHCY), inhibits atherogenic modification of LDL, interferes with vascular calcification, intervenes with platelet function, and there are interactions between H 2 S and inflammatory processes. The role of H 2 S in atherosclerotic pathogenesis highlights the mysteries of atherosclerosis and inspires the search for innovative therapeutic strategies. Here, we review the studies to date that have considered the role of H 2 S in atherosclerosis.

Cyanotic congenital heart disease and atherosclerosis

DEFF Research Database (Denmark)

Tarp, Julie Bjerre; Jensen, Annette Schophuus; Engstrøm, Thomas

2017-01-01

Improved treatment options in paediatric cardiology and congenital heart surgery have resulted in an ageing population of patients with cyanotic congenital heart disease (CCHD). The risk of acquired heart disease such as atherosclerosis increases with age.Previous studies have speculated whether...

Risk factors for atherosclerosis - can they be used to identify the ...

African Journals Online (AJOL)

Risk factors are often used in preventive care programmes to identify the patient at particular risk for developing atherosclerosis. Risk factors for atherosclerosis have also been shown to be linked to the presence of the disease at a given time, a fact that may be helpful when screening for additional atherosclerotic disease in ...

[Screening for atherosclerosis to prevent cardiovascular risk : a pro-contra debate].

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Nanchen, David; Genest, Jacques

2018-02-28

Detecting atherosclerosis using imaging techniques is the subject of intense debate in the scientific community. Among the arguments in favor of screening, a better identification or better stratification of cardiovascular risk is mentioned, compared to cardiovascular risk scores based solely on traditional risk factors, such as blood pressure or cholesterol levels. Imaging techniques are also used to monitor the progression of atherosclerosis among patients using lipid-lowering or antihypertensive drugs in primary prevention. However, several experts in recent years have challenged the clinical utility of these imaging techniques in asymptomatic adults. This article proposes a debate « for or against » to describe the main arguments for or against the use of imaging for screening for atherosclerosis.

Coronary, Carotid, and Lower-extremity Atherosclerosis and Their Interrelationship in Danish Patients with Systemic Lupus Erythematosus

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Kay, Susan Due; Poulsen, Mikael Kjaer; Diederichsen, Axel Cosmus Pyndt

2015-01-01

OBJECTIVE: Atherosclerosis is highly prevalent among patients with systemic lupus erythematosus (SLE), but has been demonstrated predominantly in non-European SLE cohorts and few investigations have included more than 1 imaging modality. We aimed to investigate the prevalence of atherosclerosis...... regression model, age (p Systemic Lupus International Collaborating Clinics (SLICC; p = 0.008) were significant independent risk factors for atherosclerosis at any vascular territory. CONCLUSION: Atherosclerosis is highly prevalent among Danish patients with SLE...

HFE gene mutations in coronary atherothrombotic disease

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Calado R.T.

2000-01-01

Full Text Available Although iron can catalyze the production of free radicals involved in LDL lipid peroxidation, the contribution of iron overload to atherosclerosis remains controversial. The description of two mutations in the HFE gene (Cys282Tyr and His63Asp related to hereditary hemochromatosis provides an opportunity to address the question of the association between iron overload and atherosclerosis. We investigated the prevalence of HFE mutations in 160 survivors of myocardial infarction with angiographically demonstrated severe coronary atherosclerotic disease, and in 160 age-, gender- and race-matched healthy control subjects. PCR amplification of genomic DNA followed by RsaI and BclI restriction enzyme digestion was used to determine the genotypes. The frequency of the mutant Cys282Tyr allele was identical among patients and controls (0.022; carrier frequency, 4.4%, whereas the mutant His63Asp allele had a frequency of 0.143 (carrier frequency, 27.5% in controls and of 0.134 (carrier frequency, 24.5% in patients. Compound heterozygotes were found in 2 of 160 (1.2% controls and in 1 of 160 (0.6% patients. The finding of a similar prevalence of Cys282Tyr and His63Asp mutations in the HFE gene among controls and patients with coronary atherothrombotic disease, indirectly questions the possibility of an association between hereditary hemochromatosis and atherosclerosis.

Genetic and pharmacological modifications of thrombin formation in apolipoprotein e-deficient mice determine atherosclerosis severity and atherothrombosis onset in a neutrophil-dependent manner.

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Julian I Borissoff

Full Text Available BACKGROUND: Variations in the blood coagulation activity, determined genetically or by medication, may alter atherosclerotic plaque progression, by influencing pleiotropic effects of coagulation proteases. Published experimental studies have yielded contradictory findings on the role of hypercoagulability in atherogenesis. We therefore sought to address this matter by extensively investigating the in vivo significance of genetic alterations and pharmacologic inhibition of thrombin formation for the onset and progression of atherosclerosis, and plaque phenotype determination. METHODOLOGY/PRINCIPAL FINDINGS: We generated transgenic atherosclerosis-prone mice with diminished coagulant or hypercoagulable phenotype and employed two distinct models of atherosclerosis. Gene-targeted 50% reduction in prothrombin (FII(-/WT:ApoE(-/- was remarkably effective in limiting disease compared to control ApoE(-/- mice, associated with significant qualitative benefits, including diminished leukocyte infiltration, altered collagen and vascular smooth muscle cell content. Genetically-imposed hypercoagulability in TM(Pro/Pro:ApoE(-/- mice resulted in severe atherosclerosis, plaque vulnerability and spontaneous atherothrombosis. Hypercoagulability was associated with a pronounced neutrophilia, neutrophil hyper-reactivity, markedly increased oxidative stress, neutrophil intraplaque infiltration and apoptosis. Administration of either the synthetic specific thrombin inhibitor Dabigatran etexilate, or recombinant activated protein C (APC, counteracted the pro-inflammatory and pro-atherogenic phenotype of pro-thrombotic TM(Pro/Pro:ApoE(-/- mice. CONCLUSIONS/SIGNIFICANCE: We provide new evidence highlighting the importance of neutrophils in the coagulation-inflammation interplay during atherogenesis. Our findings reveal that thrombin-mediated proteolysis is an unexpectedly powerful determinant of atherosclerosis in multiple distinct settings. These studies suggest that

Predictors of endothelial dysfunction and atherosclerosis in rheumatoid arthritis in Indian population

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Inderjeet Verma

2017-03-01

Conclusions: In the present study, FMD and CIMT were impaired in RA, indicating endothelial dysfunction and accelerated atherosclerosis respectively. CRP, TNF-α, serum nitrite, DAS-28 and depleted EPC population predicted endothelial dysfunction. Age, IL-6, HDL, LDL and depleted EPC population predicted accelerated atherosclerosis.

Neutrophils in atherosclerosis. A brief overview

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Hartwig, H.; Silvestre Roig, C.; Daemen, M.; Lutgens, E.; Soehnlein, O.

2015-01-01

Atherosclerosis is a chronic inflammation of the arterial wall and the continuous infiltration of leukocytes into the plaque enhances the progression of the lesion. Because of the scarce detection of neutrophils in atherosclerotic plaques compared to other immune cells, their contribution was

Food and nutrition in the prevention of atherosclerosis

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Izabela Kamila Wojarska

2018-05-01

Full Text Available Cardiovascular disease is the most frequent cause of hospitalization (15% and death (46% in Poland, as well as worldwide (31%, by reason of strenuous activity in the field of preventative healthcare in all age groups has to be taken. Preventative nutrition of atherosclerosis predicts mostly intake restriction of food containing: fatty acids, cholesterol, salt, monosaccharides and animal protein, while increasing intake of vitamins, minerals, fiber and antioxidant substances. Eating habits and nutritional status of women who are planning pregnancy have a crucial impact on its course, development of the fetus and children’s health in later years of their life. For all of cardiac patients well balanced diet is advised. In preventative care of Cardiovascular Disease it is advised to apply the diet given by a certified dietician and adjusted to fit patient’s needs. It is to remember, that besides a good diet, an important therapeutic factor of the patients with atherosclerosis is physical activity. Cardiovascular disease is a serious concern in Poland, as well as worldwide. Eating habits are playing a big role in pathogenesis and prevention of atherosclerosis.

Atherosclerosis across 4000 years of human history: the Horus study of four ancient populations.

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Thompson, Randall C; Allam, Adel H; Lombardi, Guido P; Wann, L Samuel; Sutherland, M Linda; Sutherland, James D; Soliman, Muhammad Al-Tohamy; Frohlich, Bruno; Mininberg, David T; Monge, Janet M; Vallodolid, Clide M; Cox, Samantha L; Abd el-Maksoud, Gomaa; Badr, Ibrahim; Miyamoto, Michael I; el-Halim Nur el-Din, Abd; Narula, Jagat; Finch, Caleb E; Thomas, Gregory S

2013-04-06

Atherosclerosis is thought to be a disease of modern human beings and related to contemporary lifestyles. However, its prevalence before the modern era is unknown. We aimed to evaluate preindustrial populations for atherosclerosis. We obtained whole body CT scans of 137 mummies from four different geographical regions or populations spanning more than 4000 years. Individuals from ancient Egypt, ancient Peru, the Ancestral Puebloans of southwest America, and the Unangan of the Aleutian Islands were imaged. Atherosclerosis was regarded as definite if a calcified plaque was seen in the wall of an artery and probable if calcifications were seen along the expected course of an artery. Probable or definite atherosclerosis was noted in 47 (34%) of 137 mummies and in all four geographical populations: 29 (38%) of 76 ancient Egyptians, 13 (25%) of 51 ancient Peruvians, two (40%) of five Ancestral Puebloans, and three (60%) of five Unangan hunter gatherers (p=NS). Atherosclerosis was present in the aorta in 28 (20%) mummies, iliac or femoral arteries in 25 (18%), popliteal or tibial arteries in 25 (18%), carotid arteries in 17 (12%), and coronary arteries in six (4%). Of the five vascular beds examined, atherosclerosis was present in one to two beds in 34 (25%) mummies, in three to four beds in 11 (8%), and in all five vascular beds in two (1%). Age at time of death was positively correlated with atherosclerosis (mean age at death was 43 [SD 10] years for mummies with atherosclerosis vs 32 [15] years for those without; phuman beings raises the possibility of a more basic predisposition to the disease. National Endowment for the Humanities, Paleocardiology Foundation, The National Bank of Egypt, Siemens, and St Luke's Hospital Foundation of Kansas City. Copyright © 2013 Elsevier Ltd. All rights reserved.

Intermittent Hypoxia Alters Gene Expression in Peripheral Blood Mononuclear Cells of Healthy Volunteers.

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Polotsky, Vsevolod Y; Bevans-Fonti, Shannon; Grigoryev, Dmitry N; Punjabi, Naresh M

2015-01-01

Obstructive sleep apnea is associated with high cardiovascular morbidity and mortality. Intermittent hypoxia of obstructive sleep apnea is implicated in the development and progression of insulin resistance and atherosclerosis, which have been attributed to systemic inflammation. Intermittent hypoxia leads to pro-inflammatory gene up-regulation in cell culture, but the effects of intermittent hypoxia on gene expression in humans have not been elucidated. A cross-over study was performed exposing eight healthy men to intermittent hypoxia or control conditions for five hours with peripheral blood mononuclear cell isolation before and after exposures. Total RNA was isolated followed by gene microarrays and confirmatory real time reverse transcriptase PCR. Intermittent hypoxia led to greater than two fold up-regulation of the pro-inflammatory gene toll receptor 2 (TLR2), which was not increased in the control exposure. We hypothesize that up-regulation of TLR2 by intermittent hypoxia may lead to systemic inflammation, insulin resistance and atherosclerosis in patients with obstructive sleep apnea.

Effects of catechins and caffeine on the development of atherosclerosis in mice.

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Liu, Litong; Nagai, Izumi; Gao, Ying; Matsushima, Yoshibumi; Kawai, Yoshichika; Sayama, Kazutoshi

2017-10-01

Atherosclerosis is one of the diseases related to metabolic syndrome which is caused by obesity. Previous reports have shown that green tea and its components have anti-obesity effect. We examined whether catechins and caffeine can prevent the development of atherosclerosis by oral administration, singly or in combination to the atherosclerosis model mice. Results demonstrated that the number of atherosclerotic regions in the aorta was significantly reduced by the combined treatment, and the atherosclerotic area was also improved. Serum HDL-C increased by caffeine single treatment, but no effect on the TG and TC by any treatments. Moreover, ECG illuviated to atheromatous lesions in aorta and the illuviation was enhanced by caffeine. The mRNA expression levels of LOX-1 and TNF-α showed a tendency to suppress by the combined treatment. These results indicated that the combined administration of catechins and caffeine has the inhibitory effect on the development of atherosclerosis in mice.

Murine Norovirus 4 (MNV-4 Infections Trigger Various Effects on Atherosclerosis Development

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Rafeezul Mohamed

2018-05-01

Full Text Available Murine norovirus (MNV infection can cause morbidity and mortality to immune compromised mice, especially colonies in research laboratory. MNV also can infect and propagates in macrophages and dendritic cells which trigger atherosclerosis development through the accumulation of these cells followed by the formation of foam cells. Recently, MNV-4 infection was associated with an increase in aortic sinus lesion size in LDLR (low-density lipoprotein receptor and ApoE (Apolipoprotein E deficient mice, both are well established mouse models for atherosclerosis research. Therefore, this review is intended to summarize the impacts of MNV infection in these two mouse models of atherosclerosis. The findings from all the related studies are important in understanding the fundamental effect of MNV infection on atherosclerosis development. In addition, this information could provide insight to researchers on the evaluation to eliminate MNV infection in research facility to avoid any unintended effect in their research, particularly in-vivo studies involving mice.

Biological signatures of asymptomatic extra- and intracranial atherosclerosis: the Barcelona-AsIA (Asymptomatic Intracranial Atherosclerosis) study.

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López-Cancio, Elena; Galán, Amparo; Dorado, Laura; Jiménez, Marta; Hernández, María; Millán, Mónica; Reverté, Silvia; Suñol, Anna; Barallat, Jaume; Massuet, Anna; Alzamora, Maria Teresa; Dávalos, Antonio; Arenillas, Juan Francisco

2012-10-01

Intracranial atherosclerotic disease (ICAD) remains a challenge for stroke primary and secondary prevention. Molecular pathways involved in the development of ICAD from its asymptomatic stages are largely unknown. In our population-based study, we aimed to compare the risk factor and biomarker profiles associated with intracranial and extracranial asymptomatic cerebral atherosclerosis. The Asymptomatic Intracranial Atherosclerosis (AsIA) study cohort includes a random sample population of 933 white subjects >50 years with a moderate to high vascular risk (based on REGICOR score) and without a history of stroke (64% males; mean age, 66 years). Carotid and intracranial atherosclerosis were screened by cervical and transcranial color-coded Duplex ultrasound, being moderate to severe stenoses confirmed by MR angiography. We registered clinical and anthropometric data and created a biobank with blood samples at baseline. A panel of biomarkers involved in atherothrombogenesis was determined: C-reactive protein, asymmetric-dimethylarginine, resistin, and plasminogen activator inhibitor-1. Insulin resistance was quantified by Homeostasis Model Assessment index. After multinomial regression analyses, male sex, hypertension, smoking, and alcoholic habits were independent risk factors of isolated extracranial atherosclerotic disease. Diabetes and metabolic syndrome conferred a higher risk for ICAD than for extracranial atherosclerotic disease. Moreover, metabolic syndrome and insulin resistance were independent risk factors of moderate to severe ICAD but were not risk factors of moderate to severe extracranial atherosclerotic disease. Regarding biomarkers, asymmetric-dimethylarginine was independently associated with isolated ICAD and resistin with combined ICAD-extracranial atherosclerotic disease. Our findings show distinct clinical and biological profiles in subclinical ICAD and extracranial atherosclerotic disease. Insulin resistance emerged as an important molecular

Gene activation regresses atherosclerosis, promotes health, and enhances longevity

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Luoma Pauli V

2010-07-01

Full Text Available Abstract Background Lifestyle factors and pharmacological compounds activate genetic mechanisms that influence the development of atherosclerotic and other diseases. This article reviews studies on natural and pharmacological gene activation that promotes health and enhances longevity. Results Living habits including healthy diet and regular physical activity, and pharmacotherapy, upregulate genes encoding enzymes and apolipoprotein and ATP-binding cassette transporters, acting in metabolic processes that promote health and increase survival. Cytochrome P450-enzymes, physiological factors in maintaining cholesterol homeostasis, generate oxysterols for the elimination of surplus cholesterol. Hepatic CTP:phosphocholine cytidylyltransferase-α is an important regulator of plasma HDL-C level. Gene-activators produce plasma lipoprotein profile, high HDL-C, HDL2-C and HDL-C/cholesterol ratio, which is typical of low risk of atherosclerotic disease, and also of exceptional longevity together with reduced prevalence of cardiovascular, metabolic and other diseases. High HDL contributes to protection against inflammation, oxidation and thrombosis, and associates with good cognitive function in very old people. Avoiding unhealthy stress and managing it properly promotes health and increases life expectancy. Conclusions Healthy living habits and gene-activating xenobiotics upregulate mechanisms that produce lipoprotein pattern typical of very old people and enhance longevity. Lipoprotein metabolism and large HDL2 associate with the process of living a very long life. Major future goals for health promotion are the improving of commitment to both wise lifestyle choices and drug therapy, and further the developing of new and more effective and well tolerated drugs and treatments.

Toll-Like Receptor-2 Mediates Diet and/or Pathogen Associated Atherosclerosis: Proteomic Findings

OpenAIRE

Madan, Monika; Amar, Salomon

2008-01-01

Accumulating evidence implicates a fundamental link between the immune system and atherosclerosis. Toll-like receptors are principal sensors of the innate immune system. Here we report an assessment of the role of the TLR2 pathway in atherosclerosis associated with a high-fat diet and/or bacteria in ApoE(+/-) mice.To explore the role of TLR2 in inflammation- and infection-associated atherosclerosis, 10 week-old ApoE(+/-)-TLR2(+/+), ApoE(+/-)-TLR2(+/-) and ApoE(+/-)-TLR2(-/-) mice were fed eit...

Deficiency of ABCA1 and ABCG1 in Macrophages Increases Inflammation and Accelerates Atherosclerosis in Mice

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Westerterp, Marit; Murphy, Andrew J.; Wang, Mi; Pagler, Tamara A.; Vengrenyuk, Yuliya; Kappus, Mojdeh S.; Gorman, Darren J.; Nagareddy, Prabhakara R.; Zhu, Xuewei; Abramowicz, Sandra; Parks, John S.; Welch, Carrie; Fisher, Edward A.; Wang, Nan; Yvan-Charvet, Laurent; Tall, Alan R.

2013-01-01

Rationale Plasma HDL levels are inversely correlated with atherosclerosis. Although it is widely assumed that this is due to the ability of HDL to promote cholesterol efflux from macrophage foam cells, direct experimental support for this hypothesis is lacking. Objective To assess the role of macrophage cholesterol efflux pathways in atherogenesis. Methods and Results We developed MAC-ABCDKO mice with efficient deletion of the ATP Binding Cassette Transporters A1 and G1 (ABCA1 and ABCG1) in macrophages but not in hematopoietic stem or progenitor populations. MAC-ABCDKO bone marrow (BM) was transplanted into Ldlr-/- recipients. On the chow diet, these mice had similar plasma cholesterol and blood monocyte levels but increased atherosclerosis compared to controls. On the Western type diet (WTD), MAC-ABCDKO BM transplanted Ldlr-/- mice had disproportionate atherosclerosis, considering they also had lower VLDL/LDL cholesterol levels than controls. ABCA1/G1 deficient macrophages in lesions showed increased inflammatory gene expression. Unexpectedly, WTD-fed MAC-ABCDKO BM transplanted Ldlr-/- mice displayed monocytosis and neutrophilia in the absence of HSPC proliferation. Mechanistic studies revealed increased expression of M-CSF and G-CSF in splenic macrophage foam cells, driving BM monocyte and neutrophil production. Conclusion These studies 1) show that macrophage deficiency of ABCA1/G1 is pro-atherogenic likely by promoting plaque inflammation and 2) uncover a novel positive feedback loop in which cholesterol-laden splenic macrophages signal BM progenitors to produce monocytes, with suppression by macrophage cholesterol efflux pathways. PMID:23572498

[25 year experience with using surgical correction of dislipidemia in treatment of patients with atherosclerosis].

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Sedov, V M; Mirchuk, K K; Sedletskiĭ, Iu I

2011-01-01

An analysis of results of using partial ileoshunting for the treatment of dislipidemia in 159 patients with atherosclerosis has shown that operation of partial ileoshunting has an obligatory, pronounced and lifelong lipidcorrecting effect. An antiatherogenic effect of the operation of partial ileoshunting is manifested as the improvement of the clinical course of the disease caused by atherosclerosis, by less number of thrombotic complications of atherosclerosis and less lethality from cardio-vascular diseases. At a longer follow-up period, the efficiency of partial ileoshunting as a means of secondary prophylactics of atherosclerosis is confirmed but in case of liquidation after operation of dislipoproteidemia.

Gender-Specific Association of Desacylated Ghrelin with Subclinical Atherosclerosis in the Metabolic Syndrome.

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Zanetti, Michela; Gortan Cappellari, Gianluca; Semolic, Annamaria; Burekovic, Ismet; Fonda, Maurizio; Cattin, Luigi; Barazzoni, Rocco

2017-07-01

Ghrelin, a gastric hormone with pleiotropic effects modulates vascular function and may influence atherosclerosis. Plasma ghrelin is reduced in the metabolic syndrome (MS), which is also characterized by early atherosclerosis. Ghrelin circulates in acylated (AG) and desacylated (DAG) forms. Their relative impact and that of gender on subclinical atherosclerosis in MS is unknown. To investigate potential associations of total, AG and DAG with carotid atherosclerosis and with gender in the MS. Plasma total ghrelin, AG, DAG and carotid artery IMT (cIMT) were measured in 46 MS patients (NCEP-ATP III criteria, 22M/24F). Compared with males, females had higher (p ghrelin nor AG and DAG were associated with cIMT in all MS patients nor in the male subgroup. In females, a negative (p ghrelin and AG. In multivariate modeling, DAG remained negatively (p <0.05) associated with cIMT after adjusting for plasma glucose and cardiovascular risk factors. These data indicate a negative independent association between DAG and cIMT in middle-aged women with the MS and suggest a gender-specific modulatory function of DAG in the development of atherosclerosis. Copyright © 2017 IMSS. Published by Elsevier Inc. All rights reserved.

Therapeutic implications of chemokine-mediated pathways in atherosclerosis: realistic perspectives and utopias.

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Apostolakis, Stavros; Amanatidou, Virginia; Spandidos, Demetrios A

2010-09-01

Current perspectives on the pathogenesis of atherosclerosis strongly support the involvement of inflammatory mediators in the establishment and progression of atherosclerostic lesions. Chemokine-mediated mechanisms are potent regulators of such processes by orchestrating the interactions of inflammatory cellular components of the peripheral blood with cellular components of the arterial wall. The increasing evidence supporting the role of chemokine pathways in atherosclerosis renders chemokine ligands and their receptors potential therapeutic targets. In the following review, we aim to highlight the special structural and functional features of chemokines and their receptors in respect to their roles in atherosclerosis, and examine to what extent available data can be applied in disease management practices.

Macrophages and Their Role in Atherosclerosis: Pathophysiology and Transcriptome Analysis

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Yuri V. Bobryshev

2016-01-01

Full Text Available Atherosclerosis can be regarded as a chronic inflammatory state, in which macrophages play different and important roles. Phagocytic proinflammatory cells populate growing atherosclerotic lesions, where they actively participate in cholesterol accumulation. Moreover, macrophages promote formation of complicated and unstable plaques by maintaining proinflammatory microenvironment. At the same time, anti-inflammatory macrophages contribute to tissue repair and remodelling and plaque stabilization. Macrophages therefore represent attractive targets for development of antiatherosclerotic therapy, which can aim to reduce monocyte recruitment to the lesion site, inhibit proinflammatory macrophages, or stimulate anti-inflammatory responses and cholesterol efflux. More studies are needed, however, to create a comprehensive classification of different macrophage phenotypes and to define their roles in the pathogenesis of atherosclerosis. In this review, we provide an overview of the current knowledge on macrophage diversity, activation, and plasticity in atherosclerosis and describe macrophage-based cellular tests for evaluation of potential antiatherosclerotic substances.

Biomarkers of Subclinical Atherosclerosis in Patients with Autoimmune Disorders

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Elisabetta Profumo

2012-01-01

Full Text Available Atherosclerosis is accelerated in rheumatoid arthritis (RA and psoriatic arthritis (PsA. We investigated a possible association of oxidized low-density lipoproteins (ox-LDLs, nitric oxide (NO, 3-nitrotyrosine, vitamin A, vitamin E, and β-carotene serum levels with subclinical atherosclerosis in RA and PsA. By the use of ELISA, we observed higher ox-LDL levels in patients with intima-media thickness (IMT > 1 than in patients with IMT ≤ 1 and a negative correlation between NO levels and IMT values. By the use of high-performance liquid chromatography, we determined higher levels of vitamin A in patients with PsA and IMT ≤ 1 than in controls and lower levels of β-carotene in patients with RA and PsA than in controls. β-carotene concentrations were negatively correlated to the duration of disease in RA. Our study confirms that ox-LDLs and NO may be markers of accelerated atherosclerosis in RA and PsA whereas vitamins seem to be associated only to the presence of the autoimmune disorders.

Metabolomic and Genomic Markers of Atherosclerosis as Related to Oxidative Stress, Inflammation, and Vascular Function in Twin Astronauts

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Lee, Stuart M. C.; Rana, Brinda K.; Stenger, Michael B.; Sears, Dorothy D.; Smith, Scott M.; Zwart, Sara R.; Macias, Brandon R.; Hargans, Alan R.; Sharma, Kumar; De Vivo, Immaculata

2017-01-01

BACKGROUND: Future human space travel will consist primarily of long-duration missions onboard the International Space Station (ISS) or exploration-class missions to Mars, its moons, or nearby asteroids. Astronauts participating in long-duration missions may be at an increased risk of oxidative stress and inflammatory damage due to radiation, psychological stress, altered physical activity, nutritional insufficiency, and hyperoxia during extravehicular activity. By studying one identical twin during his 1-year ISS mission and his ground-based twin, this work extends a current NASA-funded investigation to determine whether these spaceflight factors contribute to an accelerated progression of atherosclerosis. This study of twins affords a unique opportunity to examine spaceflight-related atherosclerosis risk that is independent of the confounding factors associated with different genotypes. PURPOSE: The purpose of this investigation was to determine whether biomarkers of oxidative and inflammatory stress are elevated during and after long-duration spaceflight and determine if a relation exists between levels of these biomarkers and structural and functional indices of atherosclerotic risk measured in the carotid and brachial arteries. These physiological and biochemical data will be extended by using an exploratory approach to investigate the relationship between intermediate phenotypes and risk factors for atherosclerosis and the metabolomic signature from plasma and urine samples. Since metabolites are often the indirect products of gene expression, we simultaneously assessed gene expression and DNA methylation in leukocytes. HYPOTHESIS: We predict that, compared to the ground-based twin, the space-flown twin will experience elevated biomarkers of oxidative stress and inflammatory damage, altered arterial structure and function, accelerated telomere shortening, dysregulation of genes associated with oxidative stress and inflammation, and a metabolic profile shift

Increased LDL susceptibility to oxidation accelerates future carotid artery atherosclerosis

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Aoki Toshinari

2012-01-01

Full Text Available Abstract Background We analyzed the causal relationship between LDL susceptibility to oxidation and the development of new carotid artery atherosclerosis over a period of 5 years. We previously described the determinants related to a risk of cardiovascular changes determined in a Japanese population participating in the Niigata Study, which is an ongoing epidemiological investigation of the prevention of cardiovascular diseases. Methods We selected 394 individuals (169 males and 225 females who underwent a second carotid artery ultrasonographic examination in 2001 - 2002 for the present study. The susceptibility of LDL to oxidation was determined as the photometric absorbance and electrophoretic mobility of samples that had been collected in 1996 - 1997. The measurements were compared with ultrasonographic findings obtained in 2001 - 2002. Results The multivariate-adjusted model showed that age (odds ratio (OR, 1.034; 95% confidence interval (95%CI, 1.010 - 1.059, HbA1c (OR, 1.477; 95%CI, 0.980 - 2.225, and photometric O/N (OR, 2.012; 95%CI, 1.000 - 4.051 were significant variables that could independently predict the risk of new carotid artery atherosclerosis. Conclusion The susceptibility of LDL to oxidation was a significant parameter that could predict new carotid artery atherosclerosis over a 5-year period, and higher susceptibility was associated with a higher incidence of new carotid artery atherosclerosis.

Regulation of the renin–angiotensin system in coronary atherosclerosis: A review of the literature

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Ramadan A Hammoud

2008-01-01

Full Text Available Ramadan A Hammoud, Christopher S Vaccari, Sameer H Nagamia, Bobby V KhanEmory University School of Medicine, Division of Cardiology, Grady Memorial Hospital Vascular Research Laboratory, Atlanta, Georgia, USAAbstract: Activation of the renin–angiotensin system (RAS is significant in the pathogenesis of cardiovascular disease and specifically coronary atherosclerosis. There is strong evidence that the RAS has effects on the mechanisms of action of atherosclerosis, including fibrinolytic balance, endothelial function, and plaque stability. Pharmacological inhibition of the renin angiotensin system includes angiotensin converting enzyme (ACE inhibitors, angiotensin receptor blockers (ARBs, and renin inhibitors. These agents have clinical benefits in reducing morbidity and mortality in the management of hypertension. In addition, ACE inhibitors and ARBs have shown to be effective in the management of congestive heart failure and acute myocardial infarction. This review article discusses the biochemical and molecular mechanisms involving the RAS in coronary atherosclerosis as well as the effects of RAS inhibition in clinical studies involving coronary atherosclerosis.Keywords: angiotensin II, atherosclerosis, endothelium, inflammation, vasculature

Heat Shock Proteins: Pathogenic Role in Atherosclerosis and Potential Therapeutic Implications

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Arman Kilic

2012-01-01

Full Text Available Heat shock proteins (HSPs are a highly conserved group of proteins that are constitutively expressed and function as molecular chaperones, aiding in protein folding and preventing the accumulation of misfolded proteins. In the arterial wall, HSPs have a protective role under normal physiologic conditions. In disease states, however, HSPs expressed on the vascular endothelial cell surface can act as targets for detrimental autoimmunity due to their highly conserved sequences. Developing therapeutic strategies for atherosclerosis based on HSPs is challenged by the need to balance such physiologic and pathologic roles of these proteins. This paper summarizes the role of HSPs in normal vascular wall processes as well as in the development and progression of atherosclerosis. The potential implications of HSPs in clinical therapies for atherosclerosis are also discussed.

NT-proBNP levels, atherosclerosis and vascular function in asymptomatic type 2 diabetic patients with microalbuminuria: peripheral reactive hyperaemia index but not NT-proBNP is an independent predictor of coronary atherosclerosis

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Reinhard, Henrik; Wiinberg, Niels; Hansen, Peter R

2011-01-01

for atherosclerosis is unclear. We examined the interrelationship between P-NT-proBNP, presence of atherosclerosis and/or vascular dysfunction in the coronary, carotid and peripheral arteries in asymptomatic type 2 diabetic patients with microalbuminuria that received intensive multifactorial treatment. METHODS...... AND RESULTS: P-NT-proBNP was measured in 200 asymptomatic type 2 patients without known cardiac disease that received intensive multifactorial treatment for CV risk reduction. Patients were examined for coronary, carotid and peripheral atherosclerosis, as defined by coronary calcium score=400, carotid intima...

Increased YKL-40 expression in patients with carotid atherosclerosis

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Michelsen, Axel Gottlieb; Rathcke, C.N.; Skjelland, M.

2010-01-01

atherosclerosis and 20 healthy controls. Carotid expression of YKL-40 was examined by real time RT-PCR in 57 of the patients. Regulation and effect of YKL-40 were examined in THP-1 monocytes. Results: Our main findings were: (1) serum YKL-40 levels were significantly elevated in patients with carotid...... atherosclerosis, with particularly high levels in those with symptomatic disease; (2) patients with recent ischemic symptoms (within 2 months) had higher YKL-40 mRNA levels in carotid plaque than other patients; (3) in vitro, the beta-adrenergic receptor agonist isoproterenol, toll-like receptor (TLR) 2 and TLR4...

Ultraviolet-Visible and Fluorescence Spectroscopy Techniques Are Important Diagnostic Tools during the Progression of Atherosclerosis: Diet Zinc Supplementation Retarded or Delayed Atherosclerosis

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Abdelhalim, Mohamed Anwar K.; Moussa, Sherif A. Abdelmottaleb; AL-Mohy, Yanallah Hussain

2013-01-01

Background. In this study, we examined whether UV-visible and fluorescence spectroscopy techniques detect the progression of atherosclerosis in serum of rabbits fed on high-cholesterol diet (HCD) and HCD supplemented with zinc (HCD + Zn) compared with the control. Methods. The control rabbits group was fed on 100 g/day of normal diet. The HCD group was fed on Purina Certified Rabbit Chow supplemented with 1.0% cholesterol plus 1.0% olive oil (100 g/day) for the same period. The HCD + Zn group was fed on normal Purina Certified Rabbit Chow plus 1.0% cholesterol and 1.0% olive oil supplemented with 470 ppm Zn for the same feeding period. UV-visible and fluorescence spectroscopy and biochemistry in Rabbit's blood serum and blood hematology were measured in Rabbit's blood. Results. We found that the fluorescent peak of HCD shifted toward UV-visible wavelength compared with the control using fluorescent excitation of serum at 192 nm. In addition, they showed that supplementation of zinc (350 ppm) restored the fluorescent peak closely to the control. By using UV-visible spectroscopy approach, we found that the peak absorbance of HCD (about 280 nm) was higher than that of control and that zinc supplementation seemed to decrease the absorbance. Conclusions. This study demonstrates that ultraviolet-visible and fluorescence spectroscopy techniques can be applied as noninvasive techniques on a sample blood serum for diagnosing or detecting the progression of atherosclerosis. The Zn supplementation to rabbits fed on HCD delays or retards the progression of atherosclerosis. Inducing anemia in rabbits fed on HCD delays the progression of atherosclerosis. PMID:24350281

Mouse models for atherosclerosis and pharmaceutical modifiers

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Zadelaar, A.S.M.; Kleemann, R.; Verschuren, L.; Vries-van der Weij, J. de; Hoorn, J. van der; Princen, H.M.; Kooistra, T.

2007-01-01

Atherosclerosis is a multifactorial highly-complex disease with numerous etiologies that work synergistically to promote lesion development. The ability to develop preventive and ameliorative treatments will depend on animal models that mimic the human subject metabolically and pathophysiologically

A review of Chlamydia pneumoniae and atherosclerosis

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Lindholt, Jes Sanddal; Fasting, H; Henneberg, E W

1999-01-01

Chlamydia pneumoniae is a Gram-negative obligate intracellular bacterium that causes acute upper and lower respiratory infections. Its distribution is worldwide. Seroepidemiological studies have shown an association between C. pneumoniae and atherosclerosis, and the risk of acute myocardial...

A crucial role for CDC42 in senescence-associated inflammation and atherosclerosis.

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Takashi K Ito

Full Text Available Risk factors for atherosclerosis accelerate the senescence of vascular endothelial cells and promote atherogenesis by inducing vascular inflammation. A hallmark of endothelial senescence is the persistent up-regulation of pro-inflammatory genes. We identified CDC42 signaling as a mediator of chronic inflammation associated with endothelial senescence. Inhibition of CDC42 or NF-κB signaling attenuated the sustained up-regulation of pro-inflammatory genes in senescent human endothelial cells. Endothelium-specific activation of the p53/p21 pathway, a key mediator of senescence, also resulted in up-regulation of pro-inflammatory molecules in mice, which was reversed by Cdc42 deletion in endothelial cells. Likewise, endothelial-specific deletion of Cdc42 significantly attenuated chronic inflammation and plaque formation in atherosclerotic mice. While inhibition of NF-κB suppressed the pro-inflammatory responses in acute inflammation, the influence of Cdc42 deletion was less marked. Knockdown of cdc-42 significantly down-regulated pro-inflammatory gene expression and restored the shortened lifespan to normal in mutant worms with enhanced inflammation. These findings indicate that the CDC42 pathway is critically involved in senescence-associated inflammation and could be a therapeutic target for chronic inflammation in patients with age-related diseases without compromising host defenses.

Potential Mechanisms Linking Atherosclerosis and Increased Cardiovascular Risk in COPD: Focus On Sirtuins

Science.gov (United States)

Corbi, Graziamaria; Bianco, Andrea; Turchiarelli, Viviana; Cellurale, Michele; Fatica, Federica; Daniele, Aurora; Mazzarella, Gennaro; Ferrara, Nicola

2013-01-01

The development of atherosclerosis is a multi-step process, at least in part controlled by the vascular endothelium function. Observations in humans and experimental models of atherosclerosis have identified monocyte recruitment as an early event in atherogenesis. Chronic inflammation is associated with ageing and its related diseases (e.g., atherosclerosis and chronic obstructive pulmonary disease). Recently it has been discovered that Sirtuins (NAD+-dependent deacetylases) represent a pivotal regulator of longevity and health. They appear to have a prominent role in vascular biology and regulate aspects of age-dependent atherosclerosis. Many studies demonstrate that SIRT1 exhibits anti-inflammatory properties in vitro (e.g., fatty acid-induced inflammation), in vivo (e.g., atherosclerosis, sustainment of normal immune function in knock-out mice) and in clinical studies (e.g., patients with chronic obstructive pulmonary disease). Because of a significant reduction of SIRT1 in rodent lungs exposed to cigarette smoke and in lungs of patients with chronic obstructive pulmonary disease (COPD), activation of SIRT1 may be a potential target for chronic obstructive pulmonary disease therapy. We review the inflammatory mechanisms involved in COPD-CVD coexistence and the potential role of SIRT1 in the regulation of these systems. PMID:23774840

Small animal positron emission tomography imaging and in vivo studies of atherosclerosis

DEFF Research Database (Denmark)

Hag, Anne Mette Fisker; Ripa, Rasmus Sejersten; Pedersen, Sune Folke

2013-01-01

Atherosclerosis is a growing health challenge globally, and despite our knowledge of the disease has increased over the last couple of decades, many unanswered questions remain. As molecular imaging can be used to visualize, characterize and measure biological processes at the molecular and cellu...... knowledge obtained from in vivo positron emission tomography studies of atherosclerosis performed in small animals....

Regional gene expression of LOX-1, VCAM-1, and ICAM-1 in aorta of HIV-1 transgenic rats.

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Anne Mette Fisker Hag

Full Text Available BACKGROUND: Increased prevalence of atherosclerotic cardiovascular disease in HIV-infected patients has been observed. The cause of this accelerated atherosclerosis is a matter of controversy. As clinical studies are complicated by a multiplicity of risk-factors and a low incidence of hard endpoints, studies in animal models could be attractive alternatives. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated gene expression of lectin-like oxidized-low-density-lipoprotein receptor-1 (LOX-1, vascular cell adhesion molecule-1 (VCAM-1, and intercellular adhesion molecule-1 (ICAM-1 in HIV-1 transgenic (HIV-1Tg rats; these genes are all thought to play important roles in early atherogenesis. Furthermore, the plasma level of sICAM-1 was measured. We found that gene expressions of LOX-1 and VCAM-1 were higher in the aortic arch of HIV-1Tg rats compared to controls. Also, the level of sICAM-1 was elevated in the HIV-1Tg rats compared to controls, but the ICAM-1 gene expression profile did not show any differences between the groups. CONCLUSIONS/SIGNIFICANCE: HIV-1Tg rats have gene expression patterns indicating endothelial dysfunction and accelerated atherosclerosis in aorta, suggesting that HIV-infection per se may cause atherosclerosis. This transgenic rat model may be a very promising model for further studies of the pathophysiology behind HIV-associated cardiovascular disease.

Increased Cardiovascular Events and Subclinical Atherosclerosis in Rheumatoid Arthritis Patients: 1 Year Prospective Single Centre Study.

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Piero Ruscitti

Full Text Available Several studies showed the close relationship between Rheumatoid Arthritis (RA and cerebro-cardiovascular events (CVEs and subclinical atherosclerosis. In this study, we investigated the occurrence of CVEs and subclinical atherosclerosis during the course of RA and we evaluated the possible role of both traditional cardiovascular (CV and disease related risk factors to predict the occurrence of new CVEs and the onset of subclinical atherosclerosis.We designed a single centre, bias-adjusted, prospective, observational study to investigate, in a homogeneous subset of RA patients, the occurrence of new onset of CVEs and subclinical atherosclerosis. Statistical analyses were performed to evaluate the role of traditional CV and disease-related risk factors to predict the occurrence of new CVEs and subclinical atherosclerosis.We enrolled 347 RA patients prospectively followed for 12 months. An increased percentage of patients experienced CVEs, developed subclinical atherosclerosis and was affected by systemic arterial hypertension (SAH, type 2 diabetes mellitus and metabolic syndrome (MS, at the end of follow up. Our analysis showed that the insurgence of both SAH and MS, during the follow up, the older age, the CVE familiarity and the lack of clinical response, were associated with a significantly increased risk to experience CVEs and to develop subclinical atherosclerosis.Our study quantifies the increased expected risk for CVEs in a cohort of RA patients prospectively followed for 1 year. The occurrence of both new CVEs and subclinical atherosclerosis in RA patients may be explained by inflammatory burden as well as traditional CV risk factors.

Epigenetic regulation of vascular smooth muscle cell function in atherosclerosis.

Science.gov (United States)

Findeisen, Hannes M; Kahles, Florian K; Bruemmer, Dennis

2013-04-01

Epigenetics involve heritable and acquired changes in gene transcription that occur independently of the DNA sequence. Epigenetic mechanisms constitute a hierarchic upper-level of transcriptional control through complex modifications of chromosomal components and nuclear structures. These modifications include, for example, DNA methylation or post-translational modifications of core histones; they are mediated by various chromatin-modifying enzymes; and ultimately they define the accessibility of a transcriptional complex to its target DNA. Integrating epigenetic mechanisms into the pathophysiologic concept of complex and multifactorial diseases such as atherosclerosis may significantly enhance our understanding of related mechanisms and provide promising therapeutic approaches. Although still in its infancy, intriguing scientific progress has begun to elucidate the role of epigenetic mechanisms in vascular biology, particularly in the control of smooth muscle cell phenotypes. In this review, we will summarize epigenetic pathways in smooth muscle cells, focusing on mechanisms involved in the regulation of vascular remodeling.

Analysis of glomerulosclerosis and atherosclerosis in lecithin cholesterol acyltransferase-deficient mice.

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Lambert, G; Sakai, N; Vaisman, B L; Neufeld, E B; Marteyn, B; Chan, C C; Paigen, B; Lupia, E; Thomas, A; Striker, L J; Blanchette-Mackie, J; Csako, G; Brady, J N; Costello, R; Striker, G E; Remaley, A T; Brewer, H B; Santamarina-Fojo, S

2001-05-04

To evaluate the biochemical and molecular mechanisms leading to glomerulosclerosis and the variable development of atherosclerosis in patients with familial lecithin cholesterol acyl transferase (LCAT) deficiency, we generated LCAT knockout (KO) mice and cross-bred them with apolipoprotein (apo) E KO, low density lipoprotein receptor (LDLr) KO, and cholesteryl ester transfer protein transgenic mice. LCAT-KO mice had normochromic normocytic anemia with increased reticulocyte and target cell counts as well as decreased red blood cell osmotic fragility. A subset of LCAT-KO mice accumulated lipoprotein X and developed proteinuria and glomerulosclerosis characterized by mesangial cell proliferation, sclerosis, lipid accumulation, and deposition of electron dense material throughout the glomeruli. LCAT deficiency reduced the plasma high density lipoprotein (HDL) cholesterol (-70 to -94%) and non-HDL cholesterol (-48 to -85%) levels in control, apoE-KO, LDLr-KO, and cholesteryl ester transfer protein-Tg mice. Transcriptome and Western blot analysis demonstrated up-regulation of hepatic LDLr and apoE expression in LCAT-KO mice. Despite decreased HDL, aortic atherosclerosis was significantly reduced (-35% to -99%) in all mouse models with LCAT deficiency. Our studies indicate (i) that the plasma levels of apoB containing lipoproteins rather than HDL may determine the atherogenic risk of patients with hypoalphalipoproteinemia due to LCAT deficiency and (ii) a potential etiological role for lipoproteins X in the development of glomerulosclerosis in LCAT deficiency. The availability of LCAT-KO mice characterized by lipid, hematologic, and renal abnormalities similar to familial LCAT deficiency patients will permit future evaluation of LCAT gene transfer as a possible treatment for glomerulosclerosis in LCAT-deficient states.

Patients' experience of care and treatment outcome at the Department of Clinical Oral Physiology, Dental Public Service in Stockholm.

Science.gov (United States)

Christidis, Nikolaos; Smedberg, Erica; Hägglund, Helene; Hedenberg-Magnusson, Britt

2010-01-01

Chronic pain conditions in the craniofacial region are common in the adult population with a prevalence of approximately 10%. They are included in the generic term temporomandibular disorders (TMD) and accompanied by restricted mouth opening capacity, chewing difficulties, headache and neck pain. These pain conditions cause psychological suffering, impaired social relations, and recurrent sick leave, subsequently leading to frequent use of health care, medication and consequently to a decreased quality of life. Approximately 25% of children have signs of TMD and girls are shown to be more affected than boys. These signs increase with age and in the adult population the prevalence is approximately 38-40%, also here with a higher frequency in women than in men. This study comprised 198 patients who answered an anonymous questionnaire after termination of their treatment. The study aimed to investigate the activity at the department of clinical oral physiology at the Folktandvården Eastman Institute in Stockholm, Sweden, regarding the patients and their cause of care-seeking, as well as the patients' subjective experiences of the specialist care and the treatment outcome. As a secondary aim the purpose was to investigate how/if the clinicians at the department of clinical oral physiology reached their intention of being "curious", "considerate" and "accessible". The results from this study show that the majority of the patients (57.1%) were referred from the dental public service in Stockholm. 71.7% of the patients were young women between the ages of 11 and 20. The main causes of care-seeking were temporomandibular joint clickings, followed by limited jaw movement, headache and orofacial pain. Further, an immense majority of the patients (89.9%) were very satisfied with their treatment as well as the treatment outcome. These results indicate that the clinicians at the department reached their intention of being "curious", "considerate"and "accessible", which also

Inflammatory therapeutic targets in coronary atherosclerosis – from molecular biology to clinical application

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Fabian eLinden

2014-11-01

Full Text Available Atherosclerosis is the leading cause of death worldwide. Over the past two decades, it has been clearly recognized that atherosclerosis is an inflammatory disease of the arterial wall. Accumulating data from animal experiments have supported this hypothesis, however, clinical applications making use of this knowledge remain scarce. In spite of optimal interventional and medical therapy, the risk for recurrent myocardial infarction remains by about 20% over three years after acute coronary syndromes, novel therapies to prevent atherogenesis or treat atherosclerosis are urgently needed. This review summarizes selected potential molecu-lar inflammatory targets that may be of clinical relevance. We also review recent and ongoing clinical trails that target inflammatory processes aiming at preventing adverse cardiovascular events. Overall, it seems surprising that translation of basic science into clinical practice has not been a great success. In conclusion, we propose to focus on specific efforts that promote translational science in order to improve outcome and prognosis of patients suffering from atherosclerosis.

Olive oil and postprandial hyperlipidemia: implications for atherosclerosis and metabolic syndrome.

Science.gov (United States)

Montserrat-de la Paz, Sergio; Bermudez, Beatriz; Cardelo, Magdalena P; Lopez, Sergio; Abia, Rocio; Muriana, Francisco J G

2016-12-07

Olive oil is the primary source of fat in the Mediterranean diet, which is associated with a significant improvement in health status, as measured by reduced mortality from several chronic diseases. The current pandemic of obesity, metabolic syndrome, and type 2 diabetes is intimately associated with an atherogenic dyslipidemic phenotype. The core components of the dyslipidemia of the metabolic syndrome, which most likely initiate atherosclerosis, are the "lipid triad" consisting of high plasma triglycerides, low levels of high-density lipoproteins, and a preponderance of small, dense low-density lipoproteins at fasting. However, postprandial (non-fasting) TGs (postprandial hyperlipidemia) are also recognized as an important component for atherosclerosis. Herein, the purpose of this review was to provide an update on the effects and mechanisms related to olive oil on postprandial hyperlipidemia and its implications for the onset and progression of atherosclerosis and metabolic syndrome.

Site-Specific Antioxidative Therapy for Prevention of Atherosclerosis and Cardiovascular Disease

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Hajime Otani

2013-01-01

Full Text Available Oxidative stress has been implicated in pathophysiology of aging and age-associated disease. Antioxidative medicine has become a practice for prevention of atherosclerosis. However, limited success in preventing cardiovascular disease (CVD in individuals with atherosclerosis using general antioxidants has prompted us to develop a novel antioxidative strategy to prevent atherosclerosis. Reducing visceral adipose tissue by calorie restriction (CR and regular endurance exercise represents a causative therapy for ameliorating oxidative stress. Some of the recently emerging drugs used for the treatment of CVD may be assigned as site-specific antioxidants. CR and exercise mimetic agents are the choice for individuals who are difficult to continue CR and exercise. Better understanding of molecular and cellular biology of redox signaling will pave the way for more effective antioxidative medicine for prevention of CVD and prolongation of healthy life span.

Gene targeting approaches to complex genetic diseases: atherosclerosis and essential hypertension.

OpenAIRE

Smithies, O; Maeda, N

1995-01-01

Gene targeting allows precise, predetermined changes to be made in a chosen gene in the mouse genome. To date, targeting has been used most often for generation of animals completely lacking the product of a gene of interest. The resulting "knockout" mice have confirmed some hypotheses, have upset others, but have rarely been uninformative. Models of several human genetic diseases have been produced by targeting--including Gaucher disease, cystic fibrosis, and the fragile X syndrome. These di...

The control of nuclear proliferation: future challenges. Swedish Institute of International Affairs, Stockholm, 23 April 1998

International Nuclear Information System (INIS)

ElBaradei, M.

1998-01-01

The document reproduces the text of the conference given by the Director General of the IAEA at the Swedish Institute of International Affairs in Stockholm on 23 April 1998. After a short presentation of the Agency's current verification activities, particularly in Iraq and Democratic People's Republic of Korea, the Director General focuses on the present and future role of the IAEA in the control of nuclear proliferation through its strengthened safeguards system, in the prevention of nuclear terrorism, and future challenges of controlling nuclear proliferation from both political and technical point of view

Factors associated with accelerated subclinical atherosclerosis in patients with spondyloarthritis without overt cardiovascular disease.

Science.gov (United States)

Giollo, Alessandro; Dalbeni, Andrea; Cioffi, Giovanni; Ognibeni, Federica; Gatti, Davide; Idolazzi, Luca; Orsolini, Giovanni; Minuz, Pietro; Rossini, Maurizio; Fava, Cristiano; Viapiana, Ombretta

2017-11-01

Data on the progression of atherosclerosis in spondyloarthritis (SpA) are scarce, despite a high burden of cardiovascular diseases (CVD). The aim of this study was to identify the predictors of an accelerated subclinical atherosclerosis in patients with SpA. Study participants were 66 patients free of CVD classified according to ASAS criteria. The patients were evaluated at baseline and after 13.5 ± 3.6 months. Ultrasound measurements of carotid intima-media thickness (cIMT) and distensibility coefficient (cDC) were used to assess the extent of subclinical atherosclerosis. cIMT progression rate was calculated dividing the cIMT change by the time between the scans. Accelerated atherosclerosis was defined as the top cIMT progression rate quartile. At baseline, the mean Framingham Risk Score was 14 ± 11%. At follow-up, cIMT increased in 39 patients (59%; mean difference 0.01 ± 0.10; p = 0.334). Mean cIMT progression rate was 0.01 mm/year (95% CI - 0.02 to 0.03). cDC was unchanged at follow-up. Patients with accelerated atherosclerosis (n = 16) had significantly higher serum creatinine and lower glomerular filtration rate (eGFR) at baseline. In multiple logistic regression, only eGFR and the presence of syndesmophytes were associated with an accelerated atherosclerosis, independent of traditional cardiovascular risk factors. In patients with SpA without overt CV disease, a decrease in renal function and radiographic damage are conditions associated with the development of subclinical accelerated atherosclerosis. Longitudinal assessment of cIMT could be useful to better evaluate the individual CV risk of these patients improving their prognostic stratification.

Contrasting effect of fish oil supplementation on the development of atherosclerosis in murine models

DEFF Research Database (Denmark)

Zampolli, Antonella; Bysted, Anette; Leth, Torben

2006-01-01

Objective: Increased fish oil intake is associated with protection against coronary heart disease and sudden death, while effects on atherosclerosis are controversial. We explored the effects of supplementing fish oil (rich in n-3 polyunsaturated fatty acids, PUFA) or corn oil (rich in n-6 PUFA......) in two different models of atherosclerosis. Methods and Results: Sixty-three low density lipoprotein receptor-deficient (LDLR-/-) mice and sixty-nine apolipoprotein E-deficient (apoE(-/-)) mice were fed diets without supplementations or supplemented with either 1% fish oil or 1% corn oil. In apo......E(-/-) mice, neither fish oil nor corn oil had any major impact on plasma lipids or atherosclerosis. In LDLR-/- mice, conversely, the fish oil and the corn oil group had lower levels of LDL-cholesterol and triglycerides and had lesser atherosclerosis in the aortic root and in the entire aorta (P

Torcetrapib does not reduce atherosclerosis beyond atorvastatin and induces more proinflammatory lesions than atorvastatin

NARCIS (Netherlands)

Haan, W. de; Vries-van der Weij, J. de; Hoorn, J.W.A. van der; Gautier, T.; Hoogt, C.C. van der; Westerterp, M.; Romijn, J.A.; Jukema, J.W.; Havekes, L.M.; Princen, H.M.G.; Rensen, P.C.N.

2008-01-01

BACKGROUND - Although cholesteryl ester transfer protein (CETP) inhibition is regarded as a promising strategy to reduce atherosclerosis by increasing high-density lipoprotein cholesterol, the CETP inhibitor torcetrapib given in addition to atorvastatin had no effect on atherosclerosis and even

Torcetrapib does not reduce atherosclerosis beyond atorvastatin and induces more proinflammatory lesions than atorvastatin

NARCIS (Netherlands)

de Haan, Willeke; de Vries-van der Weij, Jitske; van der Hoorn, Jose W. A.; Gautier, Thomas; van der Hoogt, Caroline C.; Westerterp, Marit; Romijn, Johannes A.; Jukema, J. Wouter; Havekes, Louis M.; Princen, Hans M. G.; Rensen, Patrick C. N.

2008-01-01

Background-Although cholesteryl ester transfer protein (CETP) inhibition is regarded as a promising strategy to reduce atherosclerosis by increasing high-density lipoprotein cholesterol, the CETP inhibitor torcetrapib given in addition to atorvastatin had no effect on atherosclerosis and even

Torcetrapib does not reduce atherosclerosis beyond atorvastatin and induces more proinflammatory lesions than atorvastatin

NARCIS (Netherlands)

de Haan, Willeke; de Vries-van der Weij, Jitske; van der Hoorn, José W. A.; Gautier, Thomas; van der Hoogt, Caroline C.; Westerterp, Marit; Romijn, Johannes A.; Jukema, J. Wouter; Havekes, Louis M.; Princen, Hans M. G.; Rensen, Patrick C. N.

2008-01-01

Although cholesteryl ester transfer protein (CETP) inhibition is regarded as a promising strategy to reduce atherosclerosis by increasing high-density lipoprotein cholesterol, the CETP inhibitor torcetrapib given in addition to atorvastatin had no effect on atherosclerosis and even increased

Age at immigration and crime in Stockholm using sibling comparisons.

Science.gov (United States)

Beckley, Amber L

2015-09-01

Past Swedish research has shown that immigrants arriving in the receiving country at an older age are less likely to commit crime than immigrants arriving at a younger age. Segmented assimilation theory argues that the family and neighborhood may be important factors affecting how age at immigration and crime are related to one another. This study used population-based register data on foreign-background males from Stockholm to test the effect of age at immigration on crime. Potential confounding from the family and neighborhood was addressed using variables and modeling strategies. Initial results, using variables to control for confounding, showed that people who immigrated around age 4 were the most likely to be suspected of a crime. When controlling for unmeasured family characteristics, it seemed that a later age at immigration was tied to a lower likelihood of crime, which does not corroborate past research findings. The effect of age at immigration, however, was not statistically significant. The results imply that future research on entire families may be a worthwhile endeavor. Copyright © 2015 Elsevier Inc. All rights reserved.

Proceedings from the Fissile Material Cut-off seminar in Stockholm

International Nuclear Information System (INIS)

Arbman, G.

1998-01-01

The Swedish Defence Research Establishment hosted an international expert seminar on the subject of verifying a prohibition of the production of fissile material for nuclear weapons purpose (cut-off) in Stockholm, June 3-5 1998. The objective of the seminar was to provide an opportunity for informal discussions among scientific and technical experts on various technical matters relating to the verification of a future Fissile Material Cut-off Treaty (FMCT). A stated aim of the seminar was to keep issues of scope to a minimum. Invited speakers and commentators were given an opportunity to present their views as written contributions. The present seminar proceedings are essentially the result of these views. In addition, short summaries of the discussions following each session are included. Although an attempt was made to be as complete and accurate as possible in reproducing these discussions, the editors apologise if some important points or statements have been omitted. If so, the main reason is that the documentation of the discussions were based on written notes, not taped recordings. Eight longer contributions have been separately indexed

Proceedings from the Fissile Material Cut-off seminar in Stockholm

Energy Technology Data Exchange (ETDEWEB)

Arbman, G. [ed.

1998-07-01

The Swedish Defence Research Establishment hosted an international expert seminar on the subject of verifying a prohibition of the production of fissile material for nuclear weapons purpose (cut-off) in Stockholm, June 3-5 1998. The objective of the seminar was to provide an opportunity for informal discussions among scientific and technical experts on various technical matters relating to the verification of a future Fissile Material Cut-off Treaty (FMCT). A stated aim of the seminar was to keep issues of scope to a minimum. Invited speakers and commentators were given an opportunity to present their views as written contributions. The present seminar proceedings are essentially the result of these views. In addition, short summaries of the discussions following each session are included. Although an attempt was made to be as complete and accurate as possible in reproducing these discussions, the editors apologise if some important points or statements have been omitted. If so, the main reason is that the documentation of the discussions were based on written notes, not taped recordings. Eight longer contributions have been separately indexed.

Fusobacterium nucleatum Alters Atherosclerosis Risk Factors and Enhances Inflammatory Markers with an Atheroprotective Immune Response in ApoE(null Mice.

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Irina M Velsko

Full Text Available The American Heart Association supports an association between periodontal disease (PD and atherosclerotic vascular disease (ASVD but does not as of yet support a causal relationship. Recently, we have shown that major periodontal pathogens Porphyromonas gingivalis and Treponema denticola are causally associated with acceleration of aortic atherosclerosis in ApoEnull hyperlipidemic mice. The aim of this study was to determine if oral infection with another significant periodontal pathogen Fusobacterium nucleatum can accelerate aortic inflammation and atherosclerosis in the aortic artery of ApoEnull mice. ApoEnull mice (n = 23 were orally infected with F. nucleatum ATCC 49256 and euthanized at 12 and 24 weeks. Periodontal disease assessments including F. nucleatum oral colonization, gingival inflammation, immune response, intrabony defects, and alveolar bone resorption were evaluated. Systemic organs were evaluated for infection, aortic sections were examined for atherosclerosis, and inflammatory markers were measured. Chronic oral infection established F. nucleatum colonization in the oral cavity, induced significant humoral IgG (P=0.0001 and IgM (P=0.001 antibody response (12 and 24 weeks, and resulted in significant (P=0.0001 alveolar bone resorption and intrabony defects. F. nucleatum genomic DNA was detected in systemic organs (heart, aorta, liver, kidney, lung indicating bacteremia. Aortic atherosclerotic plaque area was measured and showed a local inflammatory infiltrate revealed the presence of F4/80+ macrophages and CD3+ T cells. Vascular inflammation was detected by enhanced systemic cytokines (CD30L, IL-4, IL-12, oxidized LDL and serum amyloid A, as well as altered serum lipid profile (cholesterol, triglycerides, chylomicrons, VLDL, LDL, HDL, in infected mice and altered aortic gene expression in infected mice. Despite evidence for systemic infection in several organs and modulation of known atherosclerosis risk factors, aortic

Progression and regression of atherosclerosis in APOE3-Leiden transgenic mice : An immunohistochemical study

NARCIS (Netherlands)

Gijbels, M.J.J.; Cammen, M. van der; Laan, L.J.W. van der; Emeis, J.J.; Havekes, L.M.; Hofker, M.H.; Kraal, G.

1999-01-01

Apolipoprotein E3-Leiden (APOE3-Leiden) transgenic mice develop hyperlipidemia and are highly susceptible to diet-induced atherosclerosis. We have studied the progression and regression of atherosclerosis using immunohistochemistry. Female transgenic mice were fed a moderate fat diet to study

Age, gender and hypertension as major risk factors in development of subclinical atherosclerosis

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Ajla Rahimić Ćatić

2013-04-01

Full Text Available Introduction: Intima-media thickness (IMT measurement of the common carotid artery (CCA is considered as useful indicator of carotid atherosclerosis. Early detection of atherosclerosis and its associated risk factors is important to prevent stroke and heart diseases. The aim of the present study was to investigate which risk factors are better determinants of subclinical atherosclerosis, measured by common carotidartery intima media thickness (CCA-IMT.Methods: A total of 74 subjects were randomly selected in this cross – sectional study. Information on the patient’s medical history and laboratory fi ndings were obtained from their clinical records. Risk factors relevant to this study were age, gender, cigarette smoking status, diabetes, hypertension and dyslipidemia. Ultrasound scanning of carotid arteries was performed with a 7,5 MHz linear array transducer (GE Voluson730 pro. The highest value of six common carotid artery measurements was taken as the fi nal IMT. Increased CCA-IMT was defi ned when it was > 1 mm.Results: Our data demonstrated higher CCA-IMT values in male patients compared with female patients. Increased CCA-IMT was the most closely related to age (PConclusion: Age, gender and hypertension are the most important risk factors in development of carotid atherosclerosis. Early detection of atherosclerosis among high-risk populations is important in order to prevent stroke and heart diseases, which are leading causes of death worldwide.

Polyphenols and Oxidative Stress in Atherosclerosis-Related Ischemic Heart Disease and Stroke

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Yu-Chen Cheng

2017-01-01

Full Text Available Good nutrition could maintain health and life. Polyphenols are common nutrient mainly derived from fruits, vegetables, tea, coffee, cocoa, mushrooms, beverages, and traditional medicinal herbs. They are potential substances against oxidative-related diseases, for example, cardiovascular disease, specifically, atherosclerosis-related ischemic heart disease and stroke, which are health and economic problems recognized worldwide. In this study, we reviewed the risk factors for atherosclerosis, including hypertension, diabetes mellitus, hyperlipidemia, obesity, and cigarette smoking as well as the antioxidative activity of polyphenols, which could prevent the pathology of atherosclerosis, including endothelial dysfunction, low-density lipoprotein oxidation, vascular smooth muscle cell proliferation, inflammatory process by monocytes, macrophages or T lymphocytes, and platelet aggregation. The strong radical-scavenging properties of polyphenols would exhibit antioxidative and anti-inflammation effects. Polyphenols reduce ROS production by inhibiting oxidases, reducing the production of superoxide, inhibiting OxLDL formation, suppressing VSMC proliferation and migration, reducing platelet aggregation, and improving mitochondrial oxidative stress. Polyphenol consumption also inhibits the development of hypertension, diabetes mellitus, hyperlipidemia, and obesity. Despite the numerous in vivo and in vitro studies, more advanced clinical trials are necessary to confirm the efficacy of polyphenols in the treatment of atherosclerosis-related vascular diseases.

Effects of intra-abdominal sepsis on atherosclerosis in mice.

Science.gov (United States)

Kaynar, Ata Murat; Yende, Sachin; Zhu, Lin; Frederick, Daniel R; Chambers, Robin; Burton, Christine L; Carter, Melinda; Stolz, Donna Beer; Agostini, Brittani; Gregory, Alyssa D; Nagarajan, Shanmugam; Shapiro, Steven D; Angus, Derek C

2014-09-03

Sepsis and other infections are associated with late cardiovascular events. Although persistent inflammation is implicated, a causal relationship has not been established. We tested whether sepsis causes vascular inflammation and accelerates atherosclerosis. We performed prospective, randomized animal studies at a university research laboratory involving adult male ApoE-deficient (ApoE-/-) and young C57B/L6 wild-type (WT) mice. In the primary study conducted to determine whether sepsis accelerates atherosclerosis, we fed ApoE-/- mice (N = 46) an atherogenic diet for 4 months and then performed cecal ligation and puncture (CLP), followed by antibiotic therapy and fluid resuscitation or a sham operation. We followed mice for up to an additional 5 months and assessed atheroma in the descending aorta and root of the aorta. We also exposed 32 young WT mice to CLP or sham operation and followed them for 5 days to determine the effects of sepsis on vascular inflammation. ApoE-/- mice that underwent CLP had reduced activity during the first 14 days (38% reduction compared to sham; P < 0.001) and sustained weight loss compared to the sham-operated mice (-6% versus +9% change in weight after CLP or sham surgery to 5 months; P < 0.001). Despite their weight loss, CLP mice had increased atheroma (46% by 3 months and 41% increase in aortic surface area by 5 months; P = 0.03 and P = 0.004, respectively) with increased macrophage infiltration into atheroma as assessed by immunofluorescence microscopy (0.52 relative fluorescence units (rfu) versus 0.97 rfu; P = 0.04). At 5 months, peritoneal cultures were negative; however, CLP mice had elevated serum levels of interleukin 6 (IL-6) and IL-10 (each at P < 0.05). WT mice that underwent CLP had increased expression of intercellular adhesion molecule 1 in the aortic lumen versus sham at 24 hours (P = 0.01) that persisted at 120 hours (P = 0.006). Inflammatory and adhesion genes (tumor necrosis factor α, chemokine (C-C motif) ligand 2

Impact of Prediabetic Status on Coronary Atherosclerosis

Science.gov (United States)

Kurihara, Osamu; Takano, Masamichi; Yamamoto, Masanori; Shirakabe, Akihiro; Kimata, Nakahisa; Inami, Toru; Kobayashi, Nobuaki; Munakata, Ryo; Murakami, Daisuke; Inami, Shigenobu; Okamatsu, Kentaro; Ohba, Takayoshi; Ibuki, Chikao; Hata, Noritake; Seino, Yoshihiko; Mizuno, Kyoichi

2013-01-01

OBJECTIVE To determine if prediabetes is associated with atherosclerosis of coronary arteries, we evaluated the degree of coronary atherosclerosis in nondiabetic, prediabetic, and diabetic patients by using coronary angioscopy to identify plaque vulnerability based on yellow color intensity. RESEARCH DESIGN AND METHODS Sixty-seven patients with coronary artery disease (CAD) underwent angioscopic observation of multiple main-trunk coronary arteries. According to the American Diabetes Association guidelines, patients were divided into nondiabetic (n = 16), prediabetic (n = 28), and diabetic (n = 23) groups. Plaque color grade was defined as 1 (light yellow), 2 (yellow), or 3 (intense yellow) based on angioscopic findings. The number of yellow plaques (NYPs) per vessel and maximum yellow grade (MYG) were compared among the groups. RESULTS Mean NYP and MYG differed significantly between the groups (P = 0.01 and P = 0.047, respectively). These indexes were higher in prediabetic than in nondiabetic patients (P = 0.02 and P = 0.04, respectively), but similar in prediabetic and diabetic patients (P = 0.44 and P = 0.21, respectively). Diabetes and prediabetes were independent predictors of multiple yellow plaques (NYPs ≥2) in multivariate logistic regression analysis (odds ratio [OR] 10.8 [95% CI 2.09–55.6], P = 0.005; and OR 4.13 [95% CI 1.01–17.0], P = 0.049, respectively). CONCLUSIONS Coronary atherosclerosis and plaque vulnerability were more advanced in prediabetic than in nondiabetic patients and comparable between prediabetic and diabetic patients. Slight or mild disorders in glucose metabolism, such as prediabetes, could be a risk factor for CAD, as is diabetes itself. PMID:23223344

Association between diabetic retinopathy and subclinical atherosclerosis in China: Results from a community-based study.

Science.gov (United States)

Liu, Yu; Teng, Xiangyu; Zhang, Wei; Zhang, Ruifeng; Liu, Wei

2015-09-01

To evaluate the association of diabetic retinopathy with subclinical atherosclerosis in middle-aged and elderly Chinese with type 2 diabetes. A cross-sectional community-based study was performed among 1607 patients aged 40 years or older in Shanghai. Non-mydriatic digital fundus photography examination was used in diabetic retinopathy detection. Presence of elevated carotid intima-media thickness or carotid plaque was defined as subclinical atherosclerosis. The prevalence of diabetic retinopathy was 15.1% in total patients. Patients with diabetic retinopathy were more likely to have elevated carotid intima-media thickness, carotid plaque and subclinical atherosclerosis than those without diabetic retinopathy (37.9% vs 30.7%, 57.6% vs 49.6% and 64.6% vs 57.1%, respectively). The presence of diabetic retinopathy was significantly associated with increased odds of subclinical atherosclerosis (odds ratio = 1.93, 95% confidence interval = 1.03-3.60) after full adjustments. The presence of diabetic retinopathy was significantly associated with subclinical atherosclerosis in middle-aged and elderly patients with type 2 diabetics in China. © The Author(s) 2015.

Osteocalcin, Vascular Calcification, and Atherosclerosis: A Systematic Review and Meta-analysis

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Sophie A. Millar

2017-07-01

Full Text Available BackgroundOsteocalcin (OC is an intriguing hormone, concomitantly being the most abundant non-collagenous peptide found in the mineralized matrix of bone, and expanding the endocrine function of the skeleton with far-reaching extra-osseous effects. A new line of enquiry between OC and vascular calcification has emerged in response to observations that the mechanism of vascular calcification resembles that of bone mineralisation. To date, studies have reported mixed results. This systematic review and meta-analysis aimed to identify any association between OC and vascular calcification and atherosclerosis.Methods and resultsDatabases were searched for original, peer reviewed human studies. A total of 1,453 articles were retrieved, of which 46 met the eligibility criteria. Overall 26 positive, 17 negative, and 29 neutral relationships were reported for assessments between OC (either concentration in blood, presence of OC-positive cells, or histological staining for OC and extent of calcification or atherosclerosis. Studies that measured OC-positive cells or histological staining for OC reported positive relationships (11 studies. A higher percentage of Asian studies found a negative relationship (36% in contrast to European studies (6%. Studies examining carboxylated and undercarboxylated forms of OC in the blood failed to report consistent results. The meta-analysis found no significant difference between OC concentration in the blood between patients with “atherosclerosis” and control (p = 0.13, n = 1,197.ConclusionNo definitive association was determined between OC and vascular calcification or atherosclerosis; however, the presence of OC-positive cells and histological staining had a consistent positive correlation with calcification or atherosclerosis. The review highlighted several themes, which may influence OC within differing populations leading to inconclusive results. Large, longitudinal studies are required to further

Prevalence, Vascular Distribution, and Multiterritorial Extent of Subclinical Atherosclerosis in a Middle-Aged Cohort

DEFF Research Database (Denmark)

Fernández-Friera, Leticia; Peñalvo, José L; Fernández-Ortiz, Antonio

2015-01-01

age, 45.8 years; 63% male) to evaluate the systemic extent of atherosclerosis in the carotid, abdominal aortic, and iliofemoral territories by 2-/3-dimensional ultrasound and coronary artery calcification by computed tomography. The extent of subclinical atherosclerosis, defined as presence of plaque...

White Matter Lesions, Carotid and Coronary Atherosclerosis in Late-Onset Depression and Healthy Controls

DEFF Research Database (Denmark)

Devantier, Torben Albert; Nørgaard, Bjarne Linde; Poulsen, Mikael Kjær

2016-01-01

BACKGROUND: Cerebral white matter lesions (WMLs) are more common in individuals with late-onset or late-life depression. It has been proposed that carotid atherosclerosis may predispose to WMLs by inducing cerebral hypoperfusion. This hemodynamic effect of carotid atherosclerosis could be importa...

Inherited disorders of HDL metabolism and atherosclerosis

NARCIS (Netherlands)

Hovingh, G Kees; de Groot, E.P.; van der Steeg, Wim; Boekholdt, S Matthijs; Hutten, Barbara A; Kuivenhoven, J.A.; Kastelein, John J P

PURPOSE OF REVIEW: Genetic disorders of HDL metabolism are rare and, as a result, the assessment of atherosclerosis risk in individuals suffering from these disorders has been difficult. Ultrasound imaging of carotid arteries has provided a tool to assess the risk in hereditary hypo and

Inherited disorders of HDL metabolism and atherosclerosis

NARCIS (Netherlands)

Hovingh, G. Kees; de Groot, Eric; van der Steeg, Wim; Boekholdt, S. Matthijs; Hutten, Barbara A.; Kuivenhoven, Jan Albert; Kastelein, John J. P.

2005-01-01

Purpose of review Genetic disorders of HDL metabolism are rare and, as a result, the assessment of atherosclerosis risk in individuals suffering from these disorders has been difficult. Ultrasound imaging of carotid arteries has provided a tool to assess the risk in hereditary hypo and

Curcumin analog L3 alleviates diabetic atherosclerosis by multiple effects.

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Zheng, Bin; Yang, Liu; Wen, Caixia; Huang, Xiuwang; Xu, Chenxia; Lee, Kuan-Han; Xu, Jianhua

2016-03-15

L3, an analog of curcumin, is a compound isolated from a traditional Chinese medicine Turmeric. In this paper, we aims to explore the efficacy of L3 on diabetic atherosclerosis and the related mechanism. The effect of L3 was studied on glucose and lipid metabolism, antioxidant status, atherosclerosis-related indexes and pathological changes of main organs in the mice model of diabetes induced by streptozotocin and high-fat diet. The results showed that L3 treatment could meliorate dyslipidemia and hyperglycemia, reduce oxidative stress, enhance the activity of antioxidases, increase the nitric oxide level in plasma and aortic arch, decrease the production of reactive oxygen species in pancreas and lectin-like oxidized low-density lipoprotein receptor-1 expression in aortic arch, and meliorate the fatty and atherosclerotic degeneration in aortic arch, thereby preventing the development of diabetes and its complications. These results suggested that L3 can alleviate the diabetic atherosclerosis by multiple effects. This study provided scientific basis for the further research and clinical application of L3. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of ascorbic acid on prevention of hypercholesterolemia induced atherosclerosis.

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Das, S; Ray, R; Snehlata; Das, N; Srivastava, L M

2006-04-01

The notion that oxidation of lipids and propagation of free radicals may contribute to the pathogenesis of atherosclerosis is supported by a large body of evidence. To circumvent the damage caused by oxygen free radicals, antioxidants are needed which provide the much needed neutralization of free radical by allowing the pairing of electrons. In this study we have investigated the effect of ascorbic acid, a water soluble antioxidant on the development of hypercholesterolemia induced atherosclerosis in rabbits. Rabbits were made hypercholesterolemic and atherosclerotic by feeding 100 mg cholesterol/day. Different doses of ascorbic acid were administered to these rabbits. Low dose of ascorbic acid (0.5 mg/100 g body weight/day) did not have any significant effect on the percent of total area covered by atherosclerotic plaque. However, ascorbic acid when fed at a higher dose (15 mg/100 g body weight/day) was highly effective in reducing the atherogenecity. With this dose the percent of total surface area covered by atherosclerotic plaque was significantly less (p ascorbic acid may have great promise in the prevention of hypercholesterolemia induced atherosclerosis.

A rabbit model of atherosclerosis at carotid artery: MRI visualization and histopathological characterization

International Nuclear Information System (INIS)

Ma, Zhan-Long; Teng, Gao-Jun; Chen, Jun; Zhang, Hong-Ying; Cao, Ai-Hong; Ni, Yicheng

2008-01-01

To induce a rabbit model of atherosclerosis at carotid artery, to visualize the lesion evolution with magnetic resonance imaging (MRI), and to characterize the lesion types by histopathology. Atherosclerosis at the right common carotid artery (RCCA) was induced in 23 rabbits by high-lipid diet following balloon catheter injury to the endothelium. The rabbits were examined in vivo with a 1.5-T MRI and randomly divided into three groups of 6 weeks (n=6), 12 weeks (n=8) and 15 weeks (n=9) for postmortem histopathology. The lesions on both MRI and histology were categorized according to the American Heart Association (AHA) classifications of atherosclerosis. Type I and type II of atherosclerotic changes were detected at week 6, i.e., nearly normal signal intensity (SI) of the injured RCCA wall without stenosis on MRI, but with subendothelial inflammatory infiltration and proliferation of smooth muscle cells on histopathology. At week 12, 75.0% and 62.5% of type III changes were encountered on MRI and histopathology respectively with thicker injured RCCA wall of increased SI on T 1 -weighted and proton density (PD)-weighted MRI and microscopically a higher degree of plaque formation. At week 15, carotid atherosclerosis became more advanced, i.e., type IV and type V in 55.6% and 22.2% of the lesions with MRI and 55.6% and 33.3% of the lesions with histopathology, respectively. Statistical analysis revealed a significant agreement (p<0.05) between the MRI and histological findings for lesion classification (r=0.96). A rabbit model of carotid artery atherosclerosis has been successfully induced and noninvasively visualized. The atherosclerotic plaque formation evolved from type I to type V with time, which could be monitored with 1.5-T MRI and confirmed with histomorphology. This experimental setting can be applied in preclinical research on atherosclerosis. (orig.)

Functional blockage of EMMPRIN ameliorates atherosclerosis in apolipoprotein E-deficient mice.

Science.gov (United States)

Liu, Hong; Yang, Li-xia; Guo, Rui-wei; Zhu, Guo-Fu; Shi, Yan-Kun; Wang, Xian-mei; Qi, Feng; Guo, Chuan-ming; Ye, Jin-shan; Yang, Zhi-hua; Liang, Xing

2013-10-09

Extracellular matrix metalloproteinase inducer (EMMPRIN), a 58-kDa cell surface glycoprotein, has been identified as a key receptor for transmitting cellular signals mediating metalloproteinase activities, as well as inflammation and oxidative stress. Clinical evidence has revealed that EMMPRIN is expressed in human atherosclerotic plaque; however, the relationship between EMMPRIN and atherosclerosis is unclear. To evaluate the functional role of EMMPRIN in atherosclerosis, we treated apolipoprotein E-deficient (ApoE(-/-)) mice with an EMMPRIN function-blocking antibody. EMMPRIN was found to be up-regulated in ApoE(-/-) mice fed a 12-week high-fat diet in contrast to 12 weeks of normal diet. Administration of a function-blocking EMMPRIN antibody (100 μg, twice per week for 4 weeks) to ApoE(-/-) mice, starting after 12 weeks of high-fat diet feeding caused attenuated and more stable atherosclerotic lesions, less reactive oxygen stress generation on plaque, as well as down-regulation of circulating interleukin-6 and monocyte chemotactic protein-1 in ApoE(-/-) mice. The benefit of EMMPRIN functional blockage was associated with reduced metalloproteinases proteolytic activity, which delayed the circulating monocyte transmigrating into atherosclerotic lesions. EMMPRIN antibody intervention ameliorated atherosclerosis in ApoE(-/-) mice by the down-regulation of metalloproteinase activity, suggesting that EMMPRIN may be a viable therapeutic target in atherosclerosis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The role of oxidative stress and NADPH oxidase in the pathogenesis of atherosclerosis

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Dorota Bryk

2017-01-01

Full Text Available Reactive oxygen species (ROS play a key role in the pathogenesis of atherosclerosis. The main mechanisms which are involved are low-density lipoprotein oxidative modification, inactivation of nitric oxide and modulation of redox-sensitive signaling pathways. ROS contribute to several aspects of atherosclerosis including endothelial cell dysfunction, monocyte/macrophage recruitment and activation, stimulation of inflammation, and inducing smooth muscle cell migration and proliferation. NADPH oxidase is the main source of ROS in the vasculature. This enzyme consists of a membrane-bound heterodimer of gp91phox and p22phox, cytosolic regulatory subunits p47phox, p67phox and p40phox, and small GTP-binding proteins rac1 and rac 2. Seven distinct isoforms of this enzyme have been identified, of which four (NOX1, 2, 4 and 5 may have cardiovascular function. In this paper, we review the current state of knowledge concerning the role of oxidative stress and NOX enzymes in pathogenesis of atherosclerosis. Moreover, we analyze the experimental studies that explore the relationship between the NOX family and atherosclerosis.

Oxidized low-density lipoprotein-induced apoptotic dendritic cells as a novel therapy for atherosclerosis

NARCIS (Netherlands)

Frodermann, Vanessa; van Puijvelde, Gijs H M; Wierts, Laura; Lagraauw, H Maxime; Foks, Amanda C; van Santbrink, Peter J; Bot, Ilze; Kuiper, Johan; de Jager, Saskia C A

2015-01-01

Modulation of immune responses may form a powerful approach to treat atherosclerosis. It was shown that clearance of apoptotic cells results in tolerance induction to cleared Ags by dendritic cells (DCs); however, this seems impaired in atherosclerosis because Ag-specific tolerance is lacking. This

Platelets and their chemokines in atherosclerosis – clinical applications

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Philipp evon Hundelshausen

2014-08-01

Full Text Available The concept of platelets as important players in the process of atherogenesis has become increasingly accepted due to accumulating experimental and clinical evidence. Despite the progress in understanding the molecular details of atherosclerosis, particularly by using animal models, the inflammatory and thrombotic roles of activated platelet s especially in the human system remain difficult to dissect, as often only the complications of atherosclerosis i.e. stroke and myocardial infarction are definable but not the plaque burden.Platelet indices including platelet count and mean platelet volume and soluble mediators released by activated platelets are associated with atherosclerosis. The chemokine CXCL4 has multiple atherogenic activities e.g. altering the differentiation of T cells and macrophages by inhibiting neutrophil and monocyte apoptosis and by increasing the uptake of oxLDL and synergizing with CCL5. CCL5 is released and deposited on endothelium by activated platelets thereby triggering atherogenic monocyte recruitment, which can be attenuated by blocking the corresponding chemokine receptor CCR5. Atheroprotective and plaque stabilizing properties are attributed to CXCL12, which plays an important role in regenerative processes by attracting progenitor cells. Its release from luminal attached platelets accelerates endothelial healing after injury. Platelet surface molecules GPIIb/IIIa, GP1bα, P-selectin, JAM-A and the CD40/CD40L dyade are crucially involved in the interaction with endothelial cells, leukocytes and matrix molecules affecting atherogenesis. Beyond the effects on the arterial inflammatory infiltrate, platelets affect cholesterol metabolism by binding, modifying and endocytosing LDL particles via their scavenger receptors and contribute to the formation of lipid laden macrophages. Current medical therapies for the prevention of atherosclerotic therapies enable the elucidation of mechanisms linking platelets to inflammation

A Role of RIP3-Mediated Macrophage Necrosis in Atherosclerosis Development

OpenAIRE

Lin, Juan; Li, Hanjie; Yang, Min; Ren, Junming; Huang, Zhe; Han, Felicia; Huang, Jian; Ma, Jianhui; Zhang, Duanwu; Zhang, Zhirong; Wu, Jianfeng; Huang, Deli; Qiao, Muzhen; Jin, Guanghui; Wu, Qiao

2013-01-01

Necrotic death of macrophages has long been known to be present in atherosclerotic lesions but has not been studied. We examined the role of receptor interacting protein (RIP) 3, a mediator of necrotic cell death, in atherosclerosis and found that RIP3−/−;Ldlr−/− mice were no different from RIP3+/+;Ldlr−/− mice in early atherosclerosis but had significant reduction in advanced atherosclerotic lesions. Similar results were observed in Apoe−/− background mice. Bone marrow transplantation reveal...

The dynamics of social-ecological systems in urban landscapes: Stockholm and the National Urban Park, Sweden.

Science.gov (United States)

Elmqvist, T; Colding, J; Barthel, S; Borgstrom, S; Duit, A; Lundberg, J; Andersson, E; Ahrné, K; Ernstson, H; Folke, C; Bengtsson, J

2004-06-01

This study addresses social-ecological dynamics in the greater metropolitan area of Stockholm County, Sweden, with special focus on the National Urban Park (NUP). It is part of the Millennium Ecosystem Assessment (MA) and has the following specific objectives: (1) to provide scientific information on biodiversity patterns, ecosystem dynamics, and ecosystem services generated; (2) to map interplay between actors and institutions involved in management of ecosystem services; and (3) to identify strategies for strengthening social-ecological resilience. The green areas in Stockholm County deliver numerous ecosystem services, for example, air filtration, regulation of microclimate, noise reduction, surface water drainage, recreational and cultural values, nutrient retention, and pollination and seed dispersal. Recreation is among the most important services and NUP, for example, has more than 15 million visitors per year. More than 65 organizations representing 175,000 members are involved in management of ecosystem services. However, because of population increase and urban growth during the last three decades, the region displays a quite dramatic loss of green areas and biodiversity. An important future focus is how management may reduce increasing isolation of urban green areas and enhance connectivity. Comanagement should be considered where locally managed green space may function as buffer zones and for management of weak links that connect larger green areas; for example, there are three such areas around NUP identified. Preliminary results indicate that areas of informal management represent centers on which to base adaptive comanagement, with the potential to strengthen biodiversity management and resilience in the landscape.

[Psychosocial factors as predictors of atherosclerosis and cardiovascular events: contribution from animal models].

Science.gov (United States)

Alboni, Paolo; Alboni, Marco

2006-11-01

Conventional risk factors (abnormal lipids, hypertension, etc.) are independent predictors of atherosclerosis and cardiovascular events; however, these factors are not specific since about half patients with acute myocardial infarction paradoxically result at low cardiovascular risk. Recent prospective studies provide convincing evidence that some psychosocial factors are independent predictors of atherosclerosis and cardiovascular events, as well. Psychosocial factors that promote atherosclerosis can be divided into two general categories: chronic stressors, including social isolation/low social support and work stress (subordination without job control) and emotional factors, including affective disorders such as depression, severe anxiety and hostility/anger. The emotional factors, such as the chronic stressors, activate the biological mechanisms of chronic stress: increased activity of the hypothalamic-pituitary-adrenal axis, sympathetic system and inflammation processes, which have atherogenic effects, and an increase in blood coagulation. In spite of the amount of published data, psychosocial factors receive little attention in the medical setting. About 30 years ago, Kuller defined the criteria for a causal relation between a risk factor and atherosclerosis and cardiac events. The first of these criteria states that experimental research should demonstrate that any new factor would increase the extent of atherosclerosis or its complications in suitable animal models. We carried out a bibliographic research in order to investigate whether the results of the studies dealing with animal examination and experimentation support the psychosocial factors as predictors of atherosclerosis. Contributions related to some of the psychosocial factors such as social isolation, subordination and hostility/anger have been found. In these studies atherosclerotic extension has been evaluated at necroscopy; however, the incidence of cardiovascular events has not been

Disruption of Nrf2, a key inducer of antioxidant defenses, attenuates ApoE-mediated atherosclerosis in mice.

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Thomas E Sussan

Full Text Available BACKGROUND: Oxidative stress and inflammation are two critical factors that drive the formation of plaques in atherosclerosis. Nrf2 is a redox-sensitive transcription factor that upregulates a battery of antioxidative genes and cytoprotective enzymes that constitute the cellular response to oxidative stress. Our previous studies have shown that disruption of Nrf2 in mice (Nrf2(-/- causes increased susceptibility to pulmonary emphysema, asthma and sepsis due to increased oxidative stress and inflammation. Here we have tested the hypothesis that disruption of Nrf2 in mice causes increased atherosclerosis. PRINCIPAL FINDINGS: To investigate the role of Nrf2 in the development of atherosclerosis, we crossed Nrf2(-/- mice with apoliporotein E-deficient (ApoE(-/- mice. ApoE(-/- and ApoE(-/-Nrf2(-/- mice were fed an atherogenic diet for 20 weeks, and plaque area was assessed in the aortas. Surprisingly, ApoE(-/-Nrf2(-/- mice exhibited significantly smaller plaque area than ApoE(-/- controls (11.5% vs 29.5%. This decrease in plaque area observed in ApoE(-/-Nrf2(-/- mice was associated with a significant decrease in uptake of modified low density lipoproteins (AcLDL by isolated macrophages from ApoE(-/-Nrf2(-/- mice. Furthermore, atherosclerotic plaques and isolated macrophages from ApoE(-/-Nrf2(-/- mice exhibited decreased expression of the scavenger receptor CD36. CONCLUSIONS: Nrf2 is pro-atherogenic in mice, despite its antioxidative function. The net pro-atherogenic effect of Nrf2 may be mediated via positive regulation of CD36. Our data demonstrates that the potential effects of Nrf2-targeted therapies on cardiovascular disease need to be investigated.

EU Water Framework Directive and Stockholm Convention: can we reach the targets for priority substances and persistent organic pollutants?

Science.gov (United States)

Fuerhacker, Maria

2009-08-01

Water is a renewable resource and acceptable quality is important for human health, ecological and economic reasons, but human activity can cause great damage to the natural aquatic environment. Managing the water cycle in a sustainable way is the key to protect natural resources and human health. On a global level, the microbiological contamination of water sources is a major problem in connection with poverty and the United Nations Millennium Development Declaration is an important initiative to handle this problem. In terms of environmental health, persistent organic pollutants (POPs) circulate globally; as they travel long distances, they are found in remote areas far from their original source of application and can cause damage wherever they move to. On a global scale, United Nations Environmental Programme (UNEP) issued the Stockholm Convention to reduce POPs; in the European Union (EU), one intention of the Water Framework Directive (WFD) is to reach the good chemical status of waters; beside these regulations, there are other directives in support of these goals. The aim of this paper is to discuss whether the Stockholm Convention and the WFD allows meeting the targets of protection of human and environmental health, which are established in the different directives and how could we approach the targets. The aims and scopes of different directives are compiled and compared with the actual quality of water, different approaches of standard settings are compared and potential treatment options are discussed. Under the Stockholm Convention on POPs, which came into force in May 2004, governments are required to develop a National Implementation Plan (NIP) setting out how they will address their obligations under the convention and how they will take measures to eliminate or reduce the release of POPs into the environment by the use of best available techniques (BAT) and application of best environmental practices (BEP). On a European level, the WFD has been in

Study of association of CD40-CD154 gene polymorphisms with disease susceptibility and cardiovascular risk in Spanish rheumatoid arthritis patients.

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Mercedes García-Bermúdez

Full Text Available Rheumatoid arthritis (RA is a chronic inflammatory disease associated with increased cardiovascular (CV mortality. Since CD40-CD154 binding has direct consequences on inflammation process initiation, we aimed to replicate previous findings related to disease susceptibility in Spanish RA population. Furthermore, as the major complication in RA disease patients is the development of CV events due to accelerated atherosclerosis, and elevated levels of CD40L/CD154 are present in patients with acute myocardial infarction, we assessed the potential association of CD40 and CD154/CD40L gene variants with CV risk in Spanish RA patients.One thousand five hundred and seventy-five patients fulfilling the 1987 ACR classification criteria for RA and 1600 matched controls were genotyped for the CD40 rs1883832, rs4810485 and rs1535045 and CD154 rs3092952 and rs3092920 gene polymorphisms, using predesigned TaqMan single nucleotide polymorphism genotyping assays. Afterwards, we investigated the influence of CD40-CD154 gene variants in the development of CV events. Also, in a subgroup of 273 patients without history of CV events, we assessed the influence of these polymorphisms in the risk of subclinical atherosclerosis determined by carotid ultrasonography.Nominally significant differences in the allele frequencies for the rs1883832 CD40 gene polymorphism between RA patients and controls were found (p=0.038. Although we did not observe a significant association of CD40-CD154 gene variants with the development of CV events, an ANCOVA model adjusted for sex, age at the time of the ultrasonography assessment, follow-up time, traditional CV risk factors and anti-cyclic citrullinated peptide antibodies disclosed a significant association (p=0.0047 between CD40 rs1535045 polymorphism and carotid intima media thickness, a surrogate marker of atherosclerosis.Data from our pilot study indicate a potential association of rs1883832 CD40 gene polymorphism with susceptibility

Effects of apolipoprotein M in uremic atherosclerosis

DEFF Research Database (Denmark)

Bosteen, Markus Høybye; Madsen Svarrer, Eva Martha; Bisgaard, Line Stattau

2017-01-01

BACKGROUND AND AIMS: Chronic kidney disease is characterized by uremia and causes premature death, partly due to accelerated atherosclerosis. Apolipoprotein (apo) M is a plasma carrier protein for the lipid sphingosine-1-phosphate (S1P). The Apom-S1P complex associates with HDL, and may contribute...

[The impact of electronic cigarettes usage on the endothelial function and the progression of atherosclerosis].

Science.gov (United States)

Knura, Miłosz; Dragon, Jonasz; Łabuzek, Krzysztof; Okopień, Bogusław

2018-01-23

The exponetial growth in popularity of electronic cigarettes in the world markets intensifies the debate about their health effects. The smoking of traditional tabacoo products is a factor associated with the endothelium damage and progression of atherosclerosis. The elimination of the combustion process in electronic cigarettes allows to conclude that they are less harmful to a vascular endothelium than traditional tobacco products. E-cigarette aerosol contains many compounds that have an influence on initiation and progression of atherosclerosis. Nicotine protherogenic action is not fully explained. On one hand, nicotine modifies metabolic pathways leading to atherosclerosis, whereas epidemiological studies do not show an increased risk of cardiovascular disease in the population using nicotine replacement therapy or snuff. Acrolein, formaldehyde and the ultrafine particles generated during e-liquid heating have an impact on initiation and progression of atherosclerosis, but their level is lower than that of tobacco smoke. In order to assess accurately the longterm effects of e-cigarettes, it is necessary to conduct epidemiological studies measuring the effects of using e-cigarettes. It is claimed that the use of electronic cigarettes has a potential impact on the development of atherosclerosis, but is significantly lower than that of traditional cigarettes.

[Age-related macular degeneration as a local manifestation of atherosclerosis - a novel insight into pathogenesis].

Science.gov (United States)

Machalińska, Anna

2013-01-01

Age-related macular degeneration is the leading cause of irreversible visual impairment and disability among the elderly in developed countries. There is compelling evidence that atherosclerosis and age-related macular degeneration share a similar pathogenic process. The association between atherosclerosis and age-related macular degeneration has been inferred from histological, biochemical and epidemiological studies. Many published data indicate that drusen are similar in molecular composition to plaques in atherosclerosis. Furthermore, a great body of evidence has emerged over the past decade that implicates the chronic inflammatory processes in the pathogenesis and progression of both disorders. We speculate that vascular atherosclerosis and age-related macular degeneration may represent different manifestations of the same disease induced by a pathologic tissue response to the damage caused by oxidative stress and local ischemia. In this review, we characterise in detail a strong association between age-related macular degeneration and atherosclerosis development, and we postulate the hypothesis that age-related macular degeneration is a local manifestation of a systemic disease. This provides a new approach for understanding the aspects of pathogenesis and might improve the prevention and treatment of both diseases which both result from ageing of the human body.

The PATT 26 conference Stockholm, Sweden 26–30 June 2012 : Technology Education in the 21st Century

OpenAIRE

2012-01-01

PATT 26 will be held at the Royal Institute of Technology (KTH) in Stockholm, the beautiful capital of Sweden. The PATT 26 conference is part of a two-conference arrangement organized by the Royal Institute of Technology and the Centre for School Technology Education, CETIS, Linköping University, under the common heading Technology Education in the 21st Century. We hereby welcome international colleagues to this golden opportunity to share and learn more about the latest on-going and complete...

Risk factors of atherosclerosis and clinical and morphological comparisons in systemic vasculitides

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Leonid Aleksandrovich Strizhakov

2012-01-01

Full Text Available Objective: to study the incidence rates of angina, myocardial infarction (MI, stroke, and the frequency of endovascular interventions in patients with systemic vasculitides, and the incidence rate of atherosclerosis according to autopsy data. Subjects and methods. Three hundred and twenty-one patients with systemic vasculitides: Wegener's granulomatosis (n = 138, Takayasu's arteritis (n = 79, polyarteritis nodosum (n = 55, and Churg-Strauss syndrome (n = 49 were examined; 55 autopsies were analyzed in patients with the above diseases. Results. Fifty-one (15.6% of the 321 patients were diagnosed as having cardiovascular diseases (CVD: angina pectoris (7.1% and MI (3.1% and endovascular interventions (0.9%. The risk of cardiovascular events was found to be associated with traditional risk factors, such as male gender and age. Arterial hypertension, hypercholesterolaemia, and increased serum creatinine were more frequently detected in the CVD group that showed no significant differences from the non-CVD group. According to autopsy results, atherosclerosis was identified in the patients with Wegener's granulomatosis (52%, Takayasu's arteritis (50%, polyarteritis nodosum (52.6%, and Churg-Strauss syndrome (57.1%. Conclusion. CVD and atherosclerosis are common in systemic vasculitides, which requires the traditional risk factors of atherosclerosis to be actively corrected.

Effect of plasma homocysteine level and urinary monomethylarsonic acid on the risk of arsenic-associated carotid atherosclerosis

International Nuclear Information System (INIS)

Wu, M.-M.; Chiou, H.-Y.; Hsueh, Y.-M.; Hong, C.-T.; Su, C.-L.; Chang, S.-F.; Huang, W.-L.; Wang, H.-T.; Wang, Y.-H.; Hsieh, Y.-C.; Chen, C.-J.

2006-01-01

Arsenic-contaminated well water has been shown to increase the risk of atherosclerosis. Because of involving S-adenosylmethionine, homocysteine may modify the risk by interfering with the biomethylation of ingested arsenic. In this study, we assessed the effect of plasma homocysteine level and urinary monomethylarsonic acid (MMA V ) on the risk of atherosclerosis associated with arsenic. In total, 163 patients with carotid atherosclerosis and 163 controls were studied. Lifetime cumulative arsenic exposure from well water for study subjects was measured as index of arsenic exposure. Homocysteine level was determined by high-performance liquid chromatography (HPLC). Proportion of MMA V (MMA%) was calculated by dividing with total arsenic species in urine, including arsenite, arsenate, MMA V , and dimethylarsinic acid (DMA V ). Results of multiple linear regression analysis show a positive correlation of plasma homocysteine levels to the cumulative arsenic exposure after controlling for atherosclerosis status and nutritional factors (P < 0.05). This correlation, however, did not change substantially the effect of arsenic exposure on the risk of atherosclerosis as analyzed in a subsequent logistic regression model. Logistic regression analyses also show that elevated plasma homocysteine levels did not confer an independent risk for developing atherosclerosis in the study population. However, the risk of having atherosclerosis was increased to 5.4-fold (95% CI, 2.0-15.0) for the study subjects with high MMA% (≥16.5%) and high homocysteine levels (≥12.7 μmol/l) as compared to those with low MMA% (<9.9%) and low homocysteine levels (<12.7 μmol/l). Elevated homocysteinemia may exacerbate the formation of atherosclerosis related to arsenic exposure in individuals with high levels of MMA% in urine

Proinflammatory Status, Genetics and Atherosclerosis

Czech Academy of Sciences Publication Activity Database

Poledne, R.; Lorenzová, A.; Stávek, P.; Valenta, Zdeněk; Hubáček, J.; Suchánek, R.; Piťha, J.

2009-01-01

Roč. 58, Suppl. 2 (2009), S111-S118 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M06014 Grant - others:GA MŠk(CZ) 1M0510 Program:1M Institutional research plan: CEZ:AV0Z10300504 Keywords : atherosclerosis * inflammation * C-reactive protein * genetics Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.430, year: 2009 http://www.biomed.cas.cz/physiolres/pdf/58%20Suppl%202/58_S111.pdf

[Evolution of pathogenesis of atherosclerosis in phylogenesis].

Science.gov (United States)

Titov, V N

2014-01-01

The first atherosclerosis pandemics developed in phylogenesis when animals went out of the ocean, the second coincided with mutations of proteins that transferred zero-cholesterol esters, the third (present-day pandemics) results from disturbed biological function of trophology, abnormally high content of saturated fatty acids and their trans-forms in food, and blockade of bioavailability of polyenic FA (PNFA) for cells. The blood pool of ligand-free lipoproteins, phylogenetically early macrophages are only partly utilized in intima giving rise to atheromatosis. When active absorption of w-3 and w-6 PNFA is blocked, the cells synthesize by way of compensation non-physiological w-9 eicosanoids which creates the basis of pathogenesis of atherosclerosis, pathology ofautocrine regulation, and paracrine humoral regulation of cell communities and the body. A rise in the frequency of non-infectious diseases above 5-7% is regarded as pathology of biological functions and reactions. Non-physiological environmental effects should be neutralized by normalization of tropholgy function, exotrophic biological reaction. Metabolic pandemics may have two outcomes. First: (a) effective reduction to a minimum of infavourable environmental effects, i.e. normalization of the nutritive function, (b) matching it with possibilities of lipoproteins, (c) reduction of morbidity and mortality from atherosclerosis. Second: man continues to develop as in phylogenesis and adapts himself to nonphysiological nutrition. Mortality from infarction and stroke will remain high during the next 40-50 thousand years. Increased content of w-3 PNFA in food without reduction of NAF with blockade of bioavailability will further facilitate atheromatosis. Man should rely on physiological nutrition, there is no reason to rely on hypolipidemic agents. Otherwise, the second outcome awaits the mankind. Tertium non datum.

Asymmetrical distribution of atherosclerosis in the carotid artery: identical patterns across age, race, and gender

NARCIS (Netherlands)

Tajik, Parvin; Meijer, Rudy; Duivenvoorden, Raphaël; Peters, Sanne A. E.; Kastelein, John J.; Visseren, Frank J.; Crouse, John R.; Palmer, Mike K.; Raichlen, Joel S.; Grobbee, Diederick E.; Bots, Michiel L.

2012-01-01

Background: Small autopsy studies and clinical practice indicated that carotid atherosclerosis develops in an asymmetrical helical pattern coinciding with regions of low shear stress. We investigated the distribution of carotid atherosclerosis as determined by maximum carotid intima-media thickness

Aterosclerose experimental em coelhos Experimental atherosclerosis in rabbits

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Waleska C. Dornas

2010-08-01

Full Text Available Numerosas pesquisas têm sido realizadas utilizando modelos experimentais para estudar o desenvolvimento da aterosclerose com dieta induzindo hiperlipidemia. Devido ao fato de que coelhos são muito sensíveis a dietas ricas em colesterol e acumulam grandes quantidades no plasma, a utilização destes animais como modelo experimental para avaliar o desenvolvimento de aterosclerose é de grande relevância, trazendo informação sobre fatores que contribuem para progressão e regressão aplicadas a situações humanas. Sendo assim, nessa revisão a função aterogênica do colesterol é mostrada em trabalhos que incluem o coelho como modelo experimental, uma vez que este animal tornou-se o mais popular modelo experimental de aterosclerose.Many researches have been conducted in experimental models in order to study the development of atherosclerosis from hyperlipidemia-inducing diets. Since rabbits are very sensitive to cholesterol-rich diets and accumulate large amounts of cholesterol in their plasma, their use as experimental models to evaluate the development of atherosclerosis is highly relevant and brings information on factors that contribute to the progression and regression of this condition that can be applied to humans. As such, this review includes studies on the atherogenic function of cholesterol based on rabbits as the experimental model, since they have become the most largely used experimental model of atherosclerosis.

Vascular endothelial genes that are responsive to tumor necrosis factor-alpha in vitro are expressed in atherosclerotic lesions, including inhibitor of apoptosis protein-1, stannin, and two novel genes

NARCIS (Netherlands)

Horrevoets, A. J.; Fontijn, R. D.; van Zonneveld, A. J.; de Vries, C. J.; ten Cate, J. W.; Pannekoek, H.

1999-01-01

Activation and dysfunction of endothelial cells play a prominent role in patho-physiological processes such as atherosclerosis. We describe the identification by differential display of 106 cytokine-responsive gene fragments from endothelial cells, activated by monocyte conditioned medium or tumor

Endothelium Protective Function of Statins in Men and Women with Coronary Atherosclerosis

OpenAIRE

M. V. Klimushina; N. G. Gumanova; A. Ju. Gorshkov; N. E. Gavrilova; V. A. Metel'skaja; S. A. Boytsov

2016-01-01

Aim. To study the relationship between serum endothelin levels and lipid-lowering therapy in patients with confirmed coronary atherosclerosis.Material and methods. Patients (n=447; 320 men and 127 women; mean age 62.7±8.8 years) with coronary atherosclerosis, confirmed by coronary angiography, were included into the study. Serum endothelin levels were assessed by enzyme immunoassay (ELISA).Results. Negative correlation between the statins receiving and serum endothelin level was found in men ...

PDGF-DD, a novel mediator of smooth muscle cell phenotypic modulation, is upregulated in endothelial cells exposed to atherosclerosis-prone flow patterns.

Science.gov (United States)

Thomas, James A; Deaton, Rebecca A; Hastings, Nicole E; Shang, Yueting; Moehle, Christopher W; Eriksson, Ulf; Topouzis, Stavros; Wamhoff, Brian R; Blackman, Brett R; Owens, Gary K

2009-02-01

Platelet-derived growth factor (PDGF)-BB is a well-known smooth muscle (SM) cell (SMC) phenotypic modulator that signals by binding to PDGF alphaalpha-, alphabeta-, and betabeta-membrane receptors. PDGF-DD is a recently identified PDGF family member, and its role in SMC phenotypic modulation is unknown. Here we demonstrate that PDGF-DD inhibited expression of multiple SMC genes, including SM alpha-actin and SM myosin heavy chain, and upregulated expression of the potent SMC differentiation repressor gene Kruppel-like factor-4 at the mRNA and protein levels. On the basis of the results of promoter-reporter assays, changes in SMC gene expression were mediated, at least in part, at the level of transcription. Attenuation of the SMC phenotypic modulatory activity of PDGF-DD by pharmacological inhibitors of ERK phosphorylation and by a small interfering RNA to Kruppel-like factor-4 highlight the role of these two pathways in this process. PDGF-DD failed to repress SM alpha-actin and SM myosin heavy chain in mouse SMCs lacking a functional PDGF beta-receptor. Importantly, PDGF-DD expression was increased in neointimal lesions in the aortic arch region of apolipoprotein C-deficient (ApoE(-/-)) mice. Furthermore, human endothelial cells exposed to an atherosclerosis-prone flow pattern, as in vascular regions susceptible to the development of atherosclerosis, exhibited a significant increase in PDGF-DD expression. These findings demonstrate a novel activity for PDGF-DD in SMC biology and highlight the potential contribution of this molecule to SMC phenotypic modulation in the setting of disturbed blood flow.

Follicular B Cells Promote Atherosclerosis via T Cell-Mediated Differentiation Into Plasma Cells and Secreting Pathogenic Immunoglobulin G.

Science.gov (United States)

Tay, Christopher; Liu, Yu-Han; Kanellakis, Peter; Kallies, Axel; Li, Yi; Cao, Anh; Hosseini, Hamid; Tipping, Peter; Toh, Ban-Hock; Bobik, Alex; Kyaw, Tin

2018-05-01

B cells promote or protect development of atherosclerosis. In this study, we examined the role of MHCII (major histocompatibility II), CD40 (cluster of differentiation 40), and Blimp-1 (B-lymphocyte-induced maturation protein) expression by follicular B (FO B) cells in development of atherosclerosis together with the effects of IgG purified from atherosclerotic mice. Using mixed chimeric Ldlr -/- mice whose B cells are deficient in MHCII or CD40, we demonstrate that these molecules are critical for the proatherogenic actions of FO B cells. During development of atherosclerosis, these deficiencies affected T-B cell interactions, germinal center B cells, plasma cells, and IgG. As FO B cells differentiating into plasma cells require Blimp-1, we also assessed its role in the development of atherosclerosis. Blimp-1-deficient B cells greatly attenuated atherosclerosis and immunoglobulin-including IgG production, preventing IgG accumulation in atherosclerotic lesions; Blimp-1 deletion also attenuated lesion proinflammatory cytokines, apoptotic cell numbers, and necrotic core. To determine the importance of IgG for atherosclerosis, we purified IgG from atherosclerotic mice. Their transfer but not IgG from nonatherosclerotic mice into Ldlr -/- mice whose B cells are Blimp-1-deficient increased atherosclerosis; transfer was associated with IgG accumulating in atherosclerotic lesions, increased lesion inflammatory cytokines, apoptotic cell numbers, and necrotic core size. The mechanism by which FO B cells promote atherosclerosis is highly dependent on their expression of MHCII, CD40, and Blimp-1. FO B cell differentiation into IgG-producing plasma cells also is critical for their proatherogenic actions. Targeting B-T cell interactions and pathogenic IgG may provide novel therapeutic strategies to prevent atherosclerosis and its adverse cardiovascular complications. © 2018 American Heart Association, Inc.

Accelerated atherosclerosis in patients with systemic autoimmune diseases

NARCIS (Netherlands)

De Leeuw, K.; Kallenberg, Cees; Bijl, Marc; Shoenfeld, Y.; Gershwin, M.E.; Shoenfeld, Y; Gershwin, ME

2005-01-01

Systemic autoimmune diseases such as systemic lupus erythematosus and Wegener's granulomatosis are associated with a significantly increased prevalence of cardiovascular disease (CVD) compared with age- and sex-matched controls. Many risk factors are involved in the pathogenesis of atherosclerosis,

Clinical evaluation of atherosclerosis and mechanical properties of the thoracic aorta

International Nuclear Information System (INIS)

Saiki, Atsushi

1991-01-01

To evaluate the aortic wall atherosclerosis, X-ray CT and ECG gated radionuclide angiography were performed in 25 subjects. They were classified into 17 normotensive group (N) and 8 hypertensive group (HT). The time-activity curve was generated using radionuclide angiography in the portion of the thoracic aorta. The aortic wall distensibility was expressed as 100ΔV/V 0 / PP, where ΔV was difference between maximum and minimum (V 0 ) counts of the aorta, and PP was pulse pressure. The degree of the aortic wall atherosclerosis was evaluated by X-ray CT. The aortic wall CT-score was calculated from the CT-scores measured whithin the region of interest of the other margin of the aorta and of the background by X-ray CT. There was a significant correlation between aortic wall CT-score and systolic blood pressure (r=0.59, p<0.01) or aortic wall distensibility (r=-0.74, p<0.01)), but no correlation existed between aortic wall CT-score and diastolic blood pressure (r=0.11, p:NS). The aortic wall distensibility was higher and the aortic wall CT-score was lower in N-group than in HT-group, whereas there was no difference of the radius of the aorta between both groups. These results suggest that the aortic wall atherosclerosis advanced progressively in hypertensive patients and systolic blood pressure was a good predictor of the degree of the aortic atherosclerosis. (author)

Agent Based Modeling of Atherosclerosis: A Concrete Help in Personalized Treatments

Science.gov (United States)

Pappalardo, Francesco; Cincotti, Alessandro; Motta, Alfredo; Pennisi, Marzio

Atherosclerosis, a pathology affecting arterial blood vessels, is one of most common diseases of the developed countries. We present studies on the increased atherosclerosis risk using an agent based model of atherogenesis that has been previously validated using clinical data. It is well known that the major risk in atherosclerosis is the persistent high level of low density lipoprotein (LDL) concentration. However, it is not known if short period of high LDL concentration can cause irreversible damage and if reduction of the LDL concentration (either by life style or drug) can drastically or partially reduce the already acquired risk. We simulated four different clinical situations in a large set of virtual patients (200 per clinical scenario). In the first one the patients lifestyle maintains the concentration of LDL in a no risk range. This is the control case simulation. The second case is represented by patients having high level of LDL with a delay to apply appropriate treatments; The third scenario is characterized by patients with high LDL levels treated with specific drugs like statins. Finally we simulated patients that are characterized by several oxidative events (smoke, sedentary life style, assumption of alcoholic drinks and so on so forth) that effective increase the risk of LDL oxidation. Those preliminary results obviously need to be clinically investigated. It is clear, however, that SimAthero has the power to concretely help medical doctors and clinicians in choosing personalized treatments for the prevention of the atherosclerosis damages.

Endothelial GPR124 Exaggerates the Pathogenesis of Atherosclerosis by Activating Inflammation

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Dong-Mei Gong

2018-01-01

Full Text Available Background/Aims: Endothelial cell dysfunction is the principal pathological process underlying atherosclerotic cardiovascular disease. G protein-coupled receptor 124 (GPR124, an orphan receptor in the adhesion GPCR subfamily, promotes angiogenesis in the brain. In the present study, we explored the role of endothelial GPR124 in the development and progression of atherosclerosis in adult mice. Methods: Using tetracycline-inducible transgenic systems, we generated mice expressing GPR124 specifically under control of the Tie-2 promoter. The animal model of atherosclerosis was constructed by intravenously injecting AAV-PCSK9DY into tetracycline-regulated mice and feeding the mice a high-fat diet for 16 consecutive weeks. Biochemical analysis and immunohistochemistry methods were used to address the role and mechanism of GPR124 in the pathological process of atherosclerosis. Results: Higher TC (total cholesterol and LDL-C (low density lipoprotein cholesterol levels in serum and greater lipid deposition in the aortic sinus were found in atherosclerotic mice with GPR124 overexpression, coincident with the elevated proliferation of smooth muscle cells. We observed an elevation of ONOO- in the aortic sinus in this model by using immunofluorescence, and the experiments showed that the specific overexpression of GPR124 in the endothelium induced the up-regulation of CD68, NLRP3 and caspase-1 levels in the aortic sinus. Conclusion: The above results indicate that manipulating GPR124 in the endothelium may contribute to delayed pathological progression of atherosclerosis.

Prevalence and long-term clinical significance of intracranial atherosclerosis after ischaemic stroke or transient ischaemic attack

DEFF Research Database (Denmark)

Ovesen, Christian; Abild, Annemette; Christensen, Anders Fogh

2013-01-01

We investigated the prevalence and long-term risk associated with intracranial atherosclerosis identified during routine evaluation.......We investigated the prevalence and long-term risk associated with intracranial atherosclerosis identified during routine evaluation....

Magnetic Nanoparticles Conjugated with Peptides Derived from Monocyte Chemoattractant Protein-1 as a Tool for Targeting Atherosclerosis

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Chung-Wei Kao

2018-05-01

Full Text Available Atherosclerosis is a multifactorial inflammatory disease that may progress silently for long period, and it is also widely accepted as the main cause of cardiovascular diseases. To prevent atherosclerotic plaques from generating, imaging early molecular markers and quantifying the extent of disease progression are desired. During inflammation, circulating monocytes leave the bloodstream and migrate into incipient lipid accumulation in the artery wall, following conditioning by local growth factors and proinflammatory cytokines; therefore, monocyte accumulation in the arterial wall can be observed in fatty streaks, rupture-prone plaques, and experimental atherosclerosis. In this work, we synthesized monocyte-targeting iron oxide magnetic nanoparticles (MNPs, which were incorporated with the peptides derived from the chemokine receptor C-C chemokine receptor type 2 (CCR2-binding motif of monocytes chemoattractant protein-1 (MCP-1 as a diagnostic tool for potential atherosclerosis. MCP-1-motif MNPs co-localized with monocytes in in vitro fluorescence imaging. In addition, with MNPs injection in ApoE knockout mice (ApoE KO mice, the well-characterized animal model of atherosclerosis, MNPs were found in specific organs or regions which had monocytes accumulation, especially the aorta of atherosclerosis model mice, through in vivo imaging system (IVIS imaging and magnetic resonance imaging (MRI. We also performed Oil Red O staining and Prussian Blue staining to confirm the co-localization of MCP-1-motif MNPs and atherosclerosis. The results showed the promising potential of MCP-1-motif MNPs as a diagnostic agent of atherosclerosis.

Early Onset Intrauterine Growth Restriction in a Mouse Model of Gestational Hypercholesterolemia and Atherosclerosis

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Busso, Dolores; Mascareño, Lilian; Salas, Francisca; Berkowitz, Loni; Santander, Nicolás; Quiroz, Alonso; Amigo, Ludwig; Valdés, Gloria; Rigotti, Attilio

2014-01-01

The susceptibility to develop atherosclerosis is increased by intrauterine growth restriction and prenatal exposure to maternal hypercholesterolemia. Here, we studied whether mouse gestational hypercholesterolemia and atherosclerosis affected fetal development and growth at different stages of gestation. Female LDLR KO mice fed a proatherogenic, high cholesterol (HC) diet for 3 weeks before conception and during pregnancy exhibited a significant increase in non-HDL cholesterol and developed atherosclerosis. At embryonic days 12.5 (E12.5), E15.5, and E18.5, maternal gestational hypercholesterolemia and atherosclerosis were associated to a 22–24% reduction in male and female fetal weight without alterations in fetal number/litter or morphology nor placental weight or structure. Feeding the HC diet exclusively at the periconceptional period did not alter fetal growth, suggesting that maternal hypercholesterolemia affected fetal weight only after implantation. Vitamin E supplementation (1,000 UI of α-tocopherol/kg) of HC-fed females did not change the mean weight of E18.5 fetuses but reduced the percentage of fetuses exhibiting body weights below the 10th percentile of weight (HC: 90% vs. HC/VitE: 68%). In conclusion, our results showed that maternal gestational hypercholesterolemia and atherosclerosis in mice were associated to early onset fetal growth restriction and that dietary vitamin E supplementation had a beneficial impact on this condition. PMID:25295255

Non-alcoholic fatty liver disease and subclinical atherosclerosis: A comparison of metabolically- versus genetically-driven excess fat hepatic storage.

Science.gov (United States)

Di Costanzo, Alessia; D'Erasmo, Laura; Polimeni, Licia; Baratta, Francesco; Coletta, Paola; Di Martino, Michele; Loffredo, Lorenzo; Perri, Ludovica; Ceci, Fabrizio; Montali, Anna; Girelli, Gabriella; De Masi, Bruna; Angeloni, Antonio; Catalano, Carlo; Maranghi, Marianna; Del Ben, Maria; Angelico, Francesco; Arca, Marcello

2017-02-01

Non-alcoholic fatty liver disease (NAFLD) is frequently associated with atherosclerosis. However, it is unclear whether this association is related to excess fat liver storage per se or to metabolic abnormalities that typically accompany NAFLD. To investigate this, we compared individuals with hepatic steatosis driven by metabolic disturbances to those with hepatic steatosis associated with the rs738409 GG genotype in the patatin-like phospholipase domain-containing 3 gene (PNPLA3). Carotid intima-media thickness (CIMT), as a surrogate marker of subclinical atherosclerosis, was measured in 83 blood donors with the mutant GG genotype (group G), 100 patients with features of metabolic syndrome (MetS) but the wildtype CC genotype (group M), and 74 blood donors with the wildtype CC genotype (controls). Fatty liver was evaluated by ultrasonography and hepatic fat fraction (HFF) was measured using magnetic resonance (MRS/MRI) in 157 subjects. Compared with group G and controls, group M subjects were older and had increased adiposity indices, dyslipidemia, insulin resistance and elevated transaminase levels (all p hepatic steatosis), the median CIMT in group M (0.84 [0.70-0.95] mm) was significantly greater than that in group G (0.66 [0.55-0.74] mm; p < 0.001), which was similar to that in controls (0.70 [0.64-0.81] mm). Results were similar in the subgroup evaluated using MRS/MRI. Excess liver fat accumulation appeared to increase the burden of subclinical atherosclerosis only when it is associated with metabolic abnormalities. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Non-proinflammatory and responsive nanoplatforms for targeted treatment of atherosclerosis.

Science.gov (United States)

Dou, Yin; Chen, Yue; Zhang, Xiangjun; Xu, Xiaoqiu; Chen, Yidan; Guo, Jiawei; Zhang, Dinglin; Wang, Ruibing; Li, Xiaohui; Zhang, Jianxiang

2017-10-01

Atherosclerosis is the leading cause of many fatal cardiovascular and cerebrovascular diseases. Whereas nanomedicines are promising for targeted therapy of atherosclerosis, great challenges remain in development of effective, safe, and translational nanotherapies for its treatment. Herein we hypothesize that non-proinflammatory nanomaterials sensitive to low pH or high reactive oxygen species (ROS) may serve as effective platforms for triggerable delivery of anti-atherosclerotic therapeutics in cellular and tissue microenvironments of inflammation. To demonstrate this hypothesis, an acid-labile material of acetalated β-cyclodextrin (β-CD) (Ac-bCD) and a ROS-sensitive β-CD material (Ox-bCD) were separately synthesized by chemical modification of β-CD, which were formed into responsive nanoparticles (NPs). Ac-bCD NP was rapidly hydrolyzed in mildly acidic buffers, while hydrolysis of Ox-bCD NP was selectively accelerated by H 2 O 2 . Using an anti-atherosclerotic drug rapamycin (RAP), we found stimuli-responsive release of therapeutic molecules from Ac-bCD and Ox-bCD nanotherapies. Compared with non-responsive poly(lactide-co-glycolide) (PLGA)-based NP, Ac-bCD and Ox-bCD NPs showed negligible inflammatory responses in vitro and in vivo. By endocytosis in cells and intracellularly releasing cargo molecules in macrophages, responsive nanotherapies effectively inhibited macrophage proliferation and suppressed foam cell formation. After intraperitoneal (i.p.) delivery in apolipoprotein E-deficient (ApoE -/- ) mice, fluorescence imaging showed accumulation of NPs in atherosclerotic plaques. Flow cytometry analysis indicated that the lymphatic translocation mediated by neutrophils and monocytes/macrophages may contribute to atherosclerosis targeting of i.p. administered NPs, in addition to targeting via the leaky blood vessels. Correspondingly, i.p. treatment with different nanotherapies afforded desirable efficacies. Particularly, both pH and ROS

Normal LDL-Cholesterol Levels Are Associated With Subclinical Atherosclerosis in the Absence of Risk Factors.

Science.gov (United States)

Fernández-Friera, Leticia; Fuster, Valentín; López-Melgar, Beatriz; Oliva, Belén; García-Ruiz, José M; Mendiguren, José; Bueno, Héctor; Pocock, Stuart; Ibáñez, Borja; Fernández-Ortiz, Antonio; Sanz, Javier

2017-12-19

Absence of cardiovascular risk factors (CVRFs) is traditionally considered low risk for atherosclerosis; however, individuals without CVRFs, as currently defined, still have events. This study sought to identify predictors of subclinical atherosclerosis in CVRF-free individuals. Participants from the PESA (Progression of Early Subclinical Atherosclerosis) study (n = 4,184) without conventional CVRFs were evaluated (n = 1,779; 45.0 ± 4.1 years, 50.3% women). CVRF freedom was defined as no current smoking and untreated blood pressure cholesterol cholesterol (LDL-C) cholesterol ≥40 mg/dl. A subgroup with optimal CVRFs (n = 740) was also defined as having blood pressure cholesterol LDL-C was independently associated with atherosclerosis presence and extent, in both the CVRF-free and CVRF-optimal groups (odds ratio [×10 mg/dl]: 1.14 to 1.18; p LDL-C, even at levels currently considered normal, is independently associated with the presence and extent of early systemic atherosclerosis in the absence of major CVRFs. These findings support more effective LDL-C lowering for primordial prevention, even in individuals conventionally considered at optimal risk. (Progression of Early Subclinical Atherosclerosis [PESA] Study; NCT01410318). Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Metabonomics-based omics study and atherosclerosis

OpenAIRE

Wu, Duo-jiao; Zhu, Bi-jun; Wang, Xiang-dong

2011-01-01

Atherosclerosis results from dyslipidemia and systemic inflammation, associated with the strong metabolism and interaction between diet and disease. Strategies based on the global profiling of metabolism would be important to define the mechanisms involved in pathological alterations. Metabonomics is the quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modification. Metabonomics has been used in combination w...

CD8{sup +}CD25{sup +} T cells reduce atherosclerosis in apoE(−/−) mice

Energy Technology Data Exchange (ETDEWEB)

Zhou, Jianchang; Dimayuga, Paul C.; Zhao, Xiaoning; Yano, Juliana; Lio, Wai Man; Trinidad, Portia; Honjo, Tomoyuki; Cercek, Bojan; Shah, Prediman K.; Chyu, Kuang-Yuh, E-mail: Chyuk@cshs.org

2014-01-17

Highlights: •The role of a sub-population of CD8{sup +} T cells with suppressor functions was investigated in atherosclerosis. •CD8{sup +}CD25{sup +} T cells from adult apoE(−/−) mice had phenotype characteristics of T suppressor cells. •These CD8{sup +}CD25{sup +} T cells reduced CD4{sup +} T cell proliferation and CD8{sup +} cytotoxic activity in vitro. •Adoptive transfer of CD8{sup +}CD25{sup +} T cells significantly reduced atherosclerosis. •CD8{sup +}CD25{sup +} T cells have a suppressive function in atherosclerosis. -- Abstract: Background: It is increasingly evident that CD8{sup +} T cells are involved in atherosclerosis but the specific subtypes have yet to be defined. CD8{sup +}CD25{sup +} T cells exert suppressive effects on immune signaling and modulate experimental autoimmune disorders but their role in atherosclerosis remains to be determined. The phenotype and functional role of CD8{sup +}CD25{sup +} T cells in experimental atherosclerosis were investigated in this study. Methods and results: CD8{sup +}CD25{sup +} T cells were observed in atherosclerotic plaques of apoE(−/−) mice fed hypercholesterolemic diet. Characterization by flow cytometric analysis and functional evaluation using a CFSE-based proliferation assays revealed a suppressive phenotype and function of splenic CD8{sup +}CD25{sup +} T cells from apoE(−/−) mice. Depletion of CD8{sup +}CD25{sup +} from total CD8{sup +} T cells rendered higher cytolytic activity of the remaining CD8{sup +}CD25{sup −} T cells. Adoptive transfer of CD8{sup +}CD25{sup +} T cells into apoE(−/−) mice suppressed the proliferation of splenic CD4{sup +} T cells and significantly reduced atherosclerosis in recipient mice. Conclusions: Our study has identified an athero-protective role for CD8{sup +}CD25{sup +} T cells in experimental atherosclerosis.

Potential role of proteasome on c-jun related signaling in hypercholesterolemia induced atherosclerosis

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Erdi Sozen

2014-01-01

Full Text Available Atherosclerosis and its complications are major causes of death all over the world. One of the major risks of atherosclerosis is hypercholesterolemia. During atherosclerosis, oxidized low density lipoprotein (oxLDL regulates CD36-mediated activation of c-jun amino terminal kinase-1 (JNK1 and modulates matrix metalloproteinase (MMP induction which stimulates inflammation with an invasion of monocytes. Additionally, inhibition of proteasome leads to an accumulation of c-jun and phosphorylated c-jun and activation of activator protein-1 (AP-1 related increase of MMP expression. We have previously reported a significant increase in cluster of differentiation 36 (CD36 mRNA levels in hypercholesterolemic rabbits and shown that vitamin E treatment prevented the cholesterol induced increase in CD36 mRNA expression. In the present study, our aim is to identify the signaling molecules/transcription factors involved in the progression of atherosclerosis following CD36 activation in an in vivo model of hypercholesterolemic (induced by 2% cholesterol containing diet rabbits. In this direction, proteasomal activities by fluorometry and c-jun, phospo c-jun, JNK1, MMP-9 expressions by quantitative RT-PCR and immunoblotting were tested in aortic tissues. The effects of vitamin E on these changes were also investigated in this model. As a result, c-jun was phosphorylated following decreased proteasomal degradation in hypercholesterolemic group. MMP-9 expression was also increased in cholesterol group rabbits contributing to the development of atherosclerosis. In addition, vitamin E showed its effect by decreasing MMP-9 levels and phosphorylation of c-jun.

Age, gender and hypertension as major risk factors in development of subclinical atherosclerosis

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Ajla Rahimić Ćatić

2013-04-01

Full Text Available Introduction: Intima-media thickness (IMT measurement of the common carotid artery (CCA is considered as useful indicator of carotid atherosclerosis. Early detection of atherosclerosis and its associated risk factors is important to prevent stroke and heart diseases. The aim of the present study was to investigate which risk factors are better determinants of subclinical atherosclerosis, measured by common carotidartery intima media thickness (CCA-IMT.Methods: A total of 74 subjects were randomly selected in this cross – sectional study. Information on the patient’s medical history and laboratory fi ndings were obtained from their clinical records. Risk factors relevant to this study were age, gender, cigarette smoking status, diabetes, hypertension and dyslipidemia. Ultrasound scanning of carotid arteries was performed with a 7,5 MHz linear array transducer (GE Voluson730 pro. The highest value of six common carotid artery measurements was taken as the fi nal IMT. Increased CCA-IMT was defi ned when it was > 1 mm.Results: Our data demonstrated higher CCA-IMT values in male patients compared with female patients. Increased CCA-IMT was the most closely related to age (P<0.001, followed by systolic blood pressure (P=0.001, diastolic blood pressure (P=0.003 and glucose blood level (P=0.048.Conclusion: Age, gender and hypertension are the most important risk factors in development of carotid atherosclerosis. Early detection of atherosclerosis among high-risk populations is important in order to prevent stroke and heart diseases, which are leading causes of death worldwide.

Effects of Antisense Oligonucleotides against C-Reactive Protein on the Development of Atherosclerosis in WHHL Rabbits

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Qi Yu

2014-01-01

Full Text Available Increased plasma levels of C-reactive protein (CRP are closely associated with cardiovascular diseases, but whether CRP is directly involved in the pathogenesis of atherosclerosis is still under debate. Many controversial and contradictory results using transgenic mice and rabbits have been published but it is also unclear whether CRP lowering can be used for the treatment of atherosclerosis. In the current study, we examined the effects of the rabbit CRP antisense oligonucleotides (ASO on the development of atherosclerosis in WHHL rabbits. CRP ASO treatment led to a significant reduction of plasma CRP levels; however, both aortic and coronary atherosclerotic lesions were not significantly changed compared to those of control WHHL rabbits. These results suggest that inhibition of plasma CRP does not affect the development of atherosclerosis in WHHL rabbits.

Detection of subclinical atherosclerosis in asymptomatic subjects using ultrasound radiofrequency-tracking technology.

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Lili Niu

Full Text Available Atherosclerosis is a chronic and systemic disease and its developmental process involves the synergism of multiple risk factors such as hypertension, dyslipidemia, diabetes, obesity and smoking. The diagnosis of subclinical atherosclerosis is essential for strategic guidance towards suitable treatments and efficient prevention against acute cardiovascular events. This study employed ultrasound radiofrequency (RF tracking technology to characterize human carotid arteries in vivo in terms of intima-media thickness (IMT and artery stiffness, and evaluated the statistical correlation between carotid IMT and stiffness, and the number of risk factors for atherosclerosis.A total of 160 asymptomatic subjects were enrolled. Ultrasound RF-tracking technology was employed to acquire carotid IMT and stiffness parameters: maximum IMT ((MAXIMT, RF Quality IMT ((RFQIMT, distensibility coefficient (DC, compliance coefficient (CC, αindex, β index and local pulse wave velocity (PWVβ. The subjects were categorized in four groups in terms of the number of risk factors: 'zero', 'single', 'double', and 'multiple', and statistical analyses of carotid IMT and stiffness parameters were performed between these different groups.The subjects (n = 145 with (MAXIMT smaller than 1.0 mm matched the IMT criteria for non-atherosclerosis and were named as NA-subjects. Spearman's rho correlation analysis of the whole group and the NA-subjects both showed that (MAXIMT correlated positively with (RFQIMT, α, β, and PWVβ, and negatively with DC and CC (p<0.01. The analysis of covariance of NA-subjects showed significant differences between subjects with and without risk factors, and also showed significant differences between the 'zero', 'single', 'double', and 'multiple' groups.The carotid IMT and stiffness parameters obtained by the ultrasound RF-tracking technology were demonstrated to possess significant statistical correlation with the number of risk factors from 160

Vascular smooth muscle cell apoptosis is an early trigger for hypothyroid atherosclerosis.

Science.gov (United States)

Wang, Pei; Xu, Tian-Ying; Guan, Yun-Feng; Zhao, Yan; Li, Zhi-Yong; Lan, Xiao-Hong; Wang, Xia; Yang, Peng-Yuan; Kang, Zhi-Min; Vanhoutte, Paul M; Miao, Chao-Yu

2014-06-01

Endothelial dysfunction is an initial and vascular smooth muscle cell (VSMC) apoptosis, a later step of atherosclerosis. Hypothyroidism accelerates atherosclerosis. However, the early events responsible for this pro-atherosclerotic effect are unclear. Rats were resistant to induction of atherosclerosis by high cholesterol diet alone, but became susceptible in hypothyroid state achieved by administration of propylthiouracil (PTU) for 6 weeks. VSMC dysfunction and apoptosis were obvious within 1 week after PTU treatment, without signs of endothelial dysfunction. This early VSMC damage was caused by hypothyroidism but not the high cholesterol diet. In ApoE knockout mice, PTU-induced hypothyroidism triggered early VSMC apoptosis, increased oxidative stress, and accelerated atherosclerosis development. Thyroid hormone supplementation (T4, 10, or 50 μg/kg) prevented atherogenic phenotypes in hypothyroid rats and mice. In rats, thyroidectomy caused severe hypothyroidism 5 days after operation, which also led to rapid VSMC dysfunction and apoptosis. In vitro studies did not show a direct toxic effect of PTU on VSMCs. In contrast, thyroid hormone (T3, 0.75 μg/L plus T4, 50 nmol/L) exerted a direct protection against VSMC apoptosis, which was reduced by knockdown of TRα1, rather than TRβ1 and TRβ2 receptors. TRα1-mediated inhibition of apoptotic signalling of JNKs and caspase-3 contributed to the anti-apoptotic action of thyroid hormone. These findings provide an in vivo example for VSMC apoptosis as an early trigger of hypothyroidism-associated atherosclerosis, and reveal activation of TRα1 receptors to prevent VSMC apoptosis as a therapeutic strategy in this disease. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Intracranial atherosclerosis is associated with progression of neurological deficit in subcortical stroke.

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Hallevi, Hen; Chernyshev, Oleg Y; El Khoury, Ramy; Soileau, Michael J; Walker, Kyle C; Grotta, James C; Savitz, Sean I

2012-01-01

Progression of neurological deficit (PND) is a frequent complication of acute subcortical ischemic stroke (SCS). The role of intracranial atherosclerosis (IAS) in PND is controversial. Our goal was to evaluate IAS on admission, as predictor of PND in SCS patients. SCS patients were identified from our prospective database from 2004 to 2008. Clinical and laboratory data were collected from charts, and radiographic data from original radiographs. The proximal intracranial arteries were graded as patent, irregular, stenotic, or occlusion. IAS was defined as irregularity or stenosis. PND was defined as a change in the National Institutes of Health Stroke Scale >1 point. Two hundred and two SCS patients were identified. In 14%, PND occurred at a median of 2 days from onset. Univariate analysis by infarct location showed the following to be associated with PND: for anterior circulation infarcts (centrum semiovale/basal ganglia), M1 atherosclerosis (p = 0.042); for posterior circulation infarcts, vertebral artery atherosclerosis (p = 0.018). For both groups, we found a non-significant association with age (p = 0.2) and HbA1c levels (p = 0.095). No association was found with admission glucose levels. Multivariate analysis showed the following association with PND: for anterior circulation infarcts, M1 atherosclerosis (OR 4.7; 95% CI 1.2-18.8; p = 0.03); for pontine infarcts, vertebral artery atherosclerosis (OR 5.8; 95% CI 1.1-29.4; p = 0.033). There was an increase in PND likelihood with an increasing number of atherosclerotic vessels. In our cohort of SCS patients, PND was associated with IAS of the responsible vessels. These results suggest a role for IAS in the pathogenesis of PNF in SCS patients. Copyright © 2011 S. Karger AG, Basel.

Toll-like receptor-2 mediates diet and/or pathogen associated atherosclerosis: proteomic findings.

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Madan, Monika; Amar, Salomon

2008-09-12

Accumulating evidence implicates a fundamental link between the immune system and atherosclerosis. Toll-like receptors are principal sensors of the innate immune system. Here we report an assessment of the role of the TLR2 pathway in atherosclerosis associated with a high-fat diet and/or bacteria in ApoE(+/-) mice. To explore the role of TLR2 in inflammation- and infection-associated atherosclerosis, 10 week-old ApoE(+/-)-TLR2(+/+), ApoE(+/-)-TLR2(+/-) and ApoE(+/-)-TLR2(-/-) mice were fed either a high fat diet or a regular chow diet. All mice were inoculated intravenously, once per week for 24 consecutive weeks, with 50 microl live Porphyromonas gingivalis (P.g) (10(7) CFU) or vehicle (normal saline). Animals were euthanized 24 weeks after the first inoculation. ApoE(+/-)-TLR2(+/+) mice showed a significant increase in atheromatous lesions in proximal aorta and aortic tree compared to ApoE(+/-)-TLR2(+/-) and ApoE(+/-)-TLR2(-/-) mice for all diet conditions. They also displayed profound changes in plaque composition, as evidenced by increased macrophage infiltration and apoptosis, increased lipid content, and decreased smooth muscle cell mass, all reflecting an unstable plaque phenotype. SAA levels from ApoE(+/-)-TLR2(+/+) mice were significantly higher than from ApoE(+/-)-TLR2(+/-) and ApoE(+/-)-TLR2(-/-) mice. Serum cytokine analysis revealed increased levels of pro-inflammatory cytokines in ApoE(+/-)-TLR2(+/+) mice compared to ApoE(+/-)-TLR2(+/-) and TLR2(-/-) mice, irrespective of diet or bacterial challenge. ApoE(+/-)-TLR2(+/+) mice injected weekly for 24 weeks with FSL-1 (a TLR2 agonist) also demonstrated significant increases in atherosclerotic lesions, SAA and serum cytokine levels compared to ApoE(+/-)-TLR2(-/-) mice under same treatment condition. Finally, mass-spectrometry (MALDI-TOF-MS) of aortic samples analyzed by 2-dimensional gel electrophoresis differential display, identified 6 proteins upregulated greater than 2-fold in ApoE(+/-)-TLR2(+/+) mice

Toll-like receptor-2 mediates diet and/or pathogen associated atherosclerosis: proteomic findings.

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Monika Madan

2008-09-01

Full Text Available Accumulating evidence implicates a fundamental link between the immune system and atherosclerosis. Toll-like receptors are principal sensors of the innate immune system. Here we report an assessment of the role of the TLR2 pathway in atherosclerosis associated with a high-fat diet and/or bacteria in ApoE(+/- mice.To explore the role of TLR2 in inflammation- and infection-associated atherosclerosis, 10 week-old ApoE(+/--TLR2(+/+, ApoE(+/--TLR2(+/- and ApoE(+/--TLR2(-/- mice were fed either a high fat diet or a regular chow diet. All mice were inoculated intravenously, once per week for 24 consecutive weeks, with 50 microl live Porphyromonas gingivalis (P.g (10(7 CFU or vehicle (normal saline. Animals were euthanized 24 weeks after the first inoculation. ApoE(+/--TLR2(+/+ mice showed a significant increase in atheromatous lesions in proximal aorta and aortic tree compared to ApoE(+/--TLR2(+/- and ApoE(+/--TLR2(-/- mice for all diet conditions. They also displayed profound changes in plaque composition, as evidenced by increased macrophage infiltration and apoptosis, increased lipid content, and decreased smooth muscle cell mass, all reflecting an unstable plaque phenotype. SAA levels from ApoE(+/--TLR2(+/+ mice were significantly higher than from ApoE(+/--TLR2(+/- and ApoE(+/--TLR2(-/- mice. Serum cytokine analysis revealed increased levels of pro-inflammatory cytokines in ApoE(+/--TLR2(+/+ mice compared to ApoE(+/--TLR2(+/- and TLR2(-/- mice, irrespective of diet or bacterial challenge. ApoE(+/--TLR2(+/+ mice injected weekly for 24 weeks with FSL-1 (a TLR2 agonist also demonstrated significant increases in atherosclerotic lesions, SAA and serum cytokine levels compared to ApoE(+/--TLR2(-/- mice under same treatment condition. Finally, mass-spectrometry (MALDI-TOF-MS of aortic samples analyzed by 2-dimensional gel electrophoresis differential display, identified 6 proteins upregulated greater than 2-fold in ApoE(+/--TLR2(+/+ mice fed the high fat

Addition of Aspirin to a Fish Oil Rich Diet Decreases Inflammation and Atherosclerosis in ApoE-Null Mice

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Sorokin, Alexander V.; Yang, Zhi-Hong; Vaisman, Boris L.; Thacker, Seth; Yu, Zu-Xi; Sampson, Maureen; Serhan, Charles N.; Remaley, Alan T.

2016-01-01

Aspirin (ASA) is known to alter the production of potent inflammatory lipid mediators, but whether it interacts with omega-3 fatty acids (FA) from fish oil to affect atherosclerosis has not been determined. The goal was to investigate the impact of a fish oil enriched diet alone and in combination with ASA on the production of lipid mediators and atherosclerosis. ApoE−/− female mice were fed for 13 weeks one of the four following diets: Omega-3 FA deficient (OD), Omega-3 FA Rich (OR) (1.8 g Omega-3 FAs/kg • diet per day), Omega-3 FA Rich plus ASA (ORA) (0.1 g ASA/kg • diet per day), or an Omega-3 FA deficient plus ASA (ODA) with supplement levels equivalent to human doses. Plasma lipids, atherosclerosis, markers of inflammation, hepatic gene expression and aortic lipid mediators were determined. Hepatic omega-3 FAs were markedly higher in OR (9.9-fold) and ORA (7-fold) groups. Mice in both OR and ORA groups had 40% less plasma cholesterol in VLDL and LDL fractions, but aortic plaque area formation was only significantly lower in the ORA group (5.5%) compared to the OD group (2.5%). Plasma PCSK9 protein levels were approximately 70% lower in the OR and ORA groups. Pro-inflammatory aortic lipid mediators were 50–70% lower in the ODA group than in the OD group and more than 50% lower in the ORA group. In summary, less aortic plaque lesions and aortic pro-inflammatory lipid mediators were observed in mice on the fish oil diet plus ASA versus just the fish oil diet. PMID:27394692

The Sirt1 activator SRT1720 attenuates angiotensin II-induced atherosclerosis in apoE{sup −/−} mice through inhibiting vascular inflammatory response

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Chen, Yi xi; Zhang, Man; Cai, Yuehua; Zhao, Qihui; Dai, Wenjian, E-mail: wjdai@126.com

2015-10-02

Activation of the silent mating type information regulation 2 homolog 1 (SIRT1) has been shown consistent antiinflammatory function. However, little information is available on the function of SIRT1 during Angiotensin II (AngII)-induced atherosclerosis. Here we report atheroprotective effects of sirt1 activation in a model of AngII-accelerated atherosclerosis, characterized by suppression pro-inflammatory transcription factors Nuclear transcription factor (NF)-κB and Signal Transducers and Activators of Transcription. (STAT) signaling pathway, and atherosclerotic lesion macrophage content. In this model, administration of the SIRT1 agonist SRT1720 substantially attenuated AngII-accelerated atherosclerosis with decreasing blood pressure and inhibited NF-κB and STAT3 activation, which was associated with suppression of inflammatory factor and atherogenic gene expression in the artery. In vitro studies demonstrated similar changes in AngII-treated VSMCs and macrophages: SIRT1 activation inhibited the expression levels of proinflammatory factor. These studies uncover crucial proinflammatory mechanisms of AngII and highlight actions of SIRT1 activation to inhibit AngII signaling, which is atheroprotective. - Highlights: • SRT1720 reduced atherosclerotic lesion size in aortic arches and atherosclerotic lesion macrophage content. • SRT1720 could inhibit the phosphorylation of STAT3 and p65 phosphorylation and translocation. • SRT1720 could inhibit the expression of proinflammatory factor.

Rationale and protocol of a trial for prevention of diabetic atherosclerosis by using antiplatelet drugs: study of Diabetic Atherosclerosis Prevention by Cilostazol (DAPC study

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Kawamori Ryuzo

2006-08-01

Full Text Available Abstract Background Secondary treatment of arteriosclerosis may be applicable for the primary prevention of atherosclerosis in diabetic patients. This prospective, 2-year follow-up study was designed to determine the efficacy and safety of antiplatelet therapy in the prevention of atherosclerosis of diabetic subjects. Methods Patients with type 2 diabetes and arteriosclerosis obliterans from the Eastern Asian countries were registered online and randomly assigned either to the aspirin group (81–100 mg/day or the cilostazol group (100–200 mg/day in this international, 2-year, prospective follow-up interventional study. Results The primary study endpoint was changes in right and left maximum intima-media thickness of the common carotid artery. Secondary endpoints include changes in right and left maximum intima-media thickness of the internal carotid artery; semiquantitative evaluation of cerebral infarction by magnetic resonance imaging; cardiovascular events including sudden death, stroke, transient cerebral ischemic attacks, acute myocardial infarction, angina, and progression of arteriosclerosis obliterans; overall death; withdrawal; and change in ankle-brachial pressure index. Conclusion This is the first study to use an online system that was developed in Asian countries for pooling data from an international clinical trial. These findings are expected to help in the prevention of diabetic atherosclerosis and subsequent cardiovascular and cerebrovascular disease.

Oxidative stress and triglycerides as predictors of subclinical atherosclerosis in prediabetes.

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Al-Aubaidy, Hayder A; Jelinek, Herbert F

2014-03-01

The role of triglycerides in early preclinical atherosclerosis is controversial. Antioxidant markers may be associated with triglyceride levels in early preclinical atherosclerosis especially when fasting plasma glucose is raised. This cross-sectional study included 127 participants attending the Diabetes Screening Clinic, Charles Sturt University, Australia. Serum 8-hydroxy-2-deoxy-guanosine (8-OHdG) was significantly greater in the impaired fasting glucose (IFG) group compared with the control group (536.7 pg/ml ± 249.8 versus 171.4 pg/ml ± 96.9, respectively). The increase in 8-OHdG was associated with a mildly non-significant elevation in low-density lipoprotein level (3.2 ± 1.1 mmol/l) and a poor level of high-density lipoprotein (1.31 ± 0.3 mmol/l) in the IFG group. However, a significant increase in triglycerides (1.6 ± 0.97 mmol/l; P triglycerides in the absence of significant changes in reduced GSH and normal levels of cholesterol in the IFG cohort, suggesting that oxidative stress may be present and indicative of subclinical atherosclerosis.

Death by streaming or vinyl revival? Exploring the spatial dynamics and value-creating strategies of independent record shops in Stockholm

OpenAIRE

Hracs, Brian; Jansson, Johan

2017-01-01

The contemporary retail landscape is in flux and there is a growing perception that shopping at bricks and mortar stores is more expensive and time-consuming than shopping online. For music, illegal downloading and streaming have restructured the retail landscape and put thousands of record shops out of business. Yet, some retailers remain attractive consumption spaces. Drawing on a qualitative case study of independent record shops in Stockholm, this paper considers three value-creating stra...

The Prebiotic Inulin Aggravates Accelerated Atherosclerosis in Hypercholesterolemic APOE*3-Leiden Mice

OpenAIRE

Lisa R. Hoving; Margreet R. de Vries; Rob C. M. de Jong; Saeed Katiraei; Amanda Pronk; Paul H. A. Quax; Vanessa van Harmelen; Ko Willems van Dijk

2018-01-01

The prebiotic inulin has proven effective at lowering inflammation and plasma lipid levels. As atherosclerosis is provoked by both inflammation and hyperlipidemia, we aimed to determine the effect of inulin supplementation on atherosclerosis development in hypercholesterolemic APOE*3-Leiden (E3L) mice. Male E3L mice were fed a high-cholesterol (1%) diet, supplemented with or without 10% inulin for 5 weeks. At week 3, a non-constrictive cuff was placed around the right femoral artery to induce...

Impact of Hydroxychloroquine on Atherosclerosis and Vascular Stiffness in the Presence of Chronic Kidney Disease.

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Ashutosh M Shukla

Full Text Available Cardiovascular disease is the largest cause of morbidity and mortality among patients with chronic kidney disease (CKD and end-stage kidney disease, with nearly half of all deaths attributed to cardiovascular disease. Hydroxychloroquine (HCQ, an anti-inflammatory drug, has been shown to have multiple pleiotropic actions relevant to atherosclerosis. We conducted a proof-of-efficacy study to evaluate the effects of hydroxychloroquine in an animal model of atherosclerosis in ApoE knockout mice with and without chronic kidney disease. Forty male, 6-week-old mice were divided into four groups in a 2 x 2 design: sham placebo group; sham treatment group; CKD placebo group; and CKD treatment group. CKD was induced by a two-step surgical procedure. All mice received a high-fat diet through the study duration and were sacrificed after 16 weeks of therapy. Mice were monitored with ante-mortem ultrasonic echography (AUE for atherosclerosis and vascular stiffness and with post-mortem histology studies for atherosclerosis. Therapy with HCQ significantly reduced the severity of atherosclerosis in CKD mice and sham treated mice. HCQ reduced the area of aortic atherosclerosis on en face examination by approximately 60% in HCQ treated groups compared to the non-treated groups. Additionally, therapy with HCQ resulted in significant reduction in vascular endothelial dysfunction with improvement in vascular elasticity and flow patterns and better-preserved vascular wall thickness across multiple vascular beds. More importantly, we found that presence of CKD had no mitigating effect on HCQ's anti-atherosclerotic and vasculoprotective effects. These beneficial effects were not due to any significant effect of HCQ on inflammation, renal function, or lipid profile at the end of 16 weeks of therapy. This study, which demonstrates structural and functional protection against atherosclerosis by HCQ, provides a rationale to evaluate its use in CKD patients. Further studies

Oxidation of LDL and extent of peripheral atherosclerosis

NARCIS (Netherlands)

Vijver, L.P.L. van de; Kardinaal, A.F.M.; Duyvenvoorde, W. van; Kruijssen, D.A.C.M.; Grobbee, D.E.; Poppel, G. van; Princen, H.M.G.

1999-01-01

Evidence has accumulated for oxidative modification of low-density lipoproteins (LDL) to play an important role in the atherogenic process. Therefore, we investigated the relation between susceptibility of LDL to oxidation and risk of peripheral atherosclerosis among 249 men between 45 and 80 years

Intra‑operative grading of coronary artery atherosclerosis associated ...

African Journals Online (AJOL)

Background: Atherosclerosis is one of the common causes of morbidity and mortality, in postmenopausal women. Homocysteine, a sulfur‑containing amino acid product of methionine metabolism, may play an important role in the development of cardiovascular diseases. This study was designed to evaluate the relationship ...

Atherosclerosis and Nutrition with Special Reference to Populations ...

African Journals Online (AJOL)

Severe atherosclerosis and its sequelae-coronary heart disease, cerebral ... the different population groups in various stages of tran- sition. ... 'These data show how emotional challenges may produce conspicuous .... and coronary arteries of White men. ... evidence of left ventricular hypertrophy, and glucose in- tolerance ...

Relationship between Chlamydia pneumonia and helicobacter pylori with atherosclerosis

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ali Pooria

2009-01-01

Full Text Available Pooria A1, Maasoomi M2, Rafiee E3, Rezaee M4, Sabzi F5, Hossain Zadegan H6, Salehi M7, Mozaffari P8 1. Assistant Professor, Department of Surgery, Faculty of Medicine, Lorestan University of Medical Sciences 2. Professor, Department of Surgery, Faculty of Medicine, Kermanshah University of Medical Sciences, 3. Assistant Professor, Faculty of Medicine, Lorestan University of Medical Sciences, Department of Pathology 4. Associate Professor, Department of Surgery, Faculty of Medicine, Kermanshah University of Medical Sciences 5. Assistant Professor, Department of Statistics, Faculty of Health, Kermanshah University of Medical Sciences 6. Assistant Professor, Department of Microbiology, Faculty of Medicine, Lorestan University of Medical Sciences 7. Bsc in Nursing, Kermanshah University of Medical Sciences 8. Instructor, Department of Nursing, Faculty of Nursing and midwifery, Kermanshah University of Medical Sciences Abstract Background: Atherosclerosis is the most common cause of deaths in the developed countries and causes one million mortalities per year in the USA. Smoking, hypertension, diabetes, obesity, hyperlipidemia, stress, and low activity are known to be the causes of atherosclerosis. The objective of this study is to confirm the relationship between chlamydia pneumonia (Cpn, as well as helicobacter pylori (Hp and atherosclerosis. Materials and methods: In this analytical case-control study two groups of patients were studied. The first group including 30 patients over 30 years old with coronary artery disease were operated using coronary artery bypass graft. The control group included 30 persons assessed with angiography and having normal coronary arteries. The data were collected and analyzed using statistical methods. Results: The two groups were similar in terms of IgA and IgG anti-Cpn, and IgG anti- Hp but they were statistically different concerning IgA anti-Hp which had more positive cases in the case group in comparison with the

MicroRNAs as Potential Mediators for Cigarette Smoking Induced Atherosclerosis

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Yuka Yokoyama

2018-04-01

Full Text Available Smoking increases the risk of atherosclerosis-related events, such as myocardial infarction and ischemic stroke. Recent studies have examined the expression levels of altered microRNAs (miRNAs in various diseases. The profiles of tissue miRNAs can be potentially used in diagnosis or prognosis. However, there are limited studies on miRNAs following exposure to cigarette smoke (CS. The present study was designed to dissect the effects and cellular/molecular mechanisms of CS-induced atherosclerogenesis. Apolipoprotein E knockout (ApoE KO mice were exposed to CS for five days a week for two months at low (two puffs/min for 40 min/day or high dose (two puffs/min for 120 min/day. We measured the area of atherosclerotic plaques in the aorta, representing the expression of miRNAs after the exposure period. Two-month exposure to the high dose of CS significantly increased the plaque area in aortic arch, and significantly upregulated the expression of atherosclerotic markers (VCAM-1, ICAM-1, MCP1, p22phox, and gp91phox. Exposure to the high dose of CS also significantly upregulated the miRNA-155 level in the aortic tissues of ApoE KO mice. Moreover, the expression level of miR-126 tended to be downregulated and that of miR-21 tended to be upregulated in ApoE KO mice exposed to the high dose of CS, albeit statistically insignificant. The results suggest that CS induces atherosclerosis through increased vascular inflammation and NADPH oxidase expression and also emphasize the importance of miRNAs in the pathogenesis of CS-induced atherosclerosis. Our findings provide evidence for miRNAs as potential mediators of inflammation and atherosclerosis induced by CS.

Melanocortin 1 Receptor Deficiency Promotes Atherosclerosis in Apolipoprotein E-/- Mice.

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Rinne, Petteri; Kadiri, James J; Velasco-Delgado, Mauricio; Nuutinen, Salla; Viitala, Miro; Hollmén, Maija; Rami, Martina; Savontaus, Eriika; Steffens, Sabine

2018-02-01

The MC1-R (melanocortin 1 receptor) is expressed by monocytes and macrophages where it mediates anti-inflammatory actions. MC1-R also protects against macrophage foam cell formation primarily by promoting cholesterol efflux through the ABCA1 (ATP-binding cassette transporter subfamily A member 1) and ABCG1 (ATP-binding cassette transporter subfamily G member 1). In this study, we aimed to investigate whether global deficiency in MC1-R signaling affects the development of atherosclerosis. Apoe -/- (apolipoprotein E deficient) mice were crossed with recessive yellow (Mc1r e/e ) mice carrying dysfunctional MC1-R and fed a high-fat diet to induce atherosclerosis. Apoe -/- Mc1r e/e mice developed significantly larger atherosclerotic lesions in the aortic sinus and in the whole aorta compared with Apoe -/- controls. In terms of plaque composition, MC1-R deficiency was associated with less collagen and smooth muscle cells and increased necrotic core, indicative of more vulnerable lesions. These changes were accompanied by reduced Abca1 and Abcg1 expression in the aorta. Furthermore, Apoe -/- Mc1r e/e mice showed a defect in bile acid metabolism that aggravated high-fat diet-induced hypercholesterolemia and hepatic lipid accumulation. Flow cytometric analysis of leukocyte profile revealed that dysfunctional MC1-R enhanced arterial accumulation of classical Ly6C high monocytes and macrophages, effects that were evident in mice fed a normal chow diet but not under high-fat diet conditions. In support of enhanced arterial recruitment of Ly6C high monocytes, these cells had increased expression of L-selectin and P-selectin glycoprotein ligand 1. The present study highlights the importance of MC1-R in the development of atherosclerosis. Deficiency in MC1-R signaling exacerbates atherosclerosis by disturbing cholesterol handling and by increasing arterial monocyte accumulation. © 2017 The Authors.

Atorvastatin Improves Inflammatory Response in Atherosclerosis by Upregulating the Expression of GARP

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Zhao, Xiaoqi; Liu, Yuzhou; Zhong, Yucheng; Liu, Bo; Yu, Kunwu; Shi, Huairui; Zhu, Ruirui; Meng, Kai; Zhang, Wei; Wu, Bangwei

2015-01-01

Regulatory T cells play an important role in the progression of atherosclerosis. GARP is a newly biological membrane molecule existed on activated Tregs, which is related to the release of TGF-β. The antiatherosclerosis effects of statins partly depend on their multiple immune modulatory potencies. In this paper, we present that atorvastatin could upregulate the expression of GARP and TGF-β in CD4+ T cells and increase the numbers of CD4+LAP+ and CD4+Foxp3+ regulatory T cells in ApoE−/− mice. Also, we indicate that atorvastatin promotes the aggregation of GARP+ and Foxp3+ cells and secretory of the TGF-β1 in atherosclerotic plaques. Furthermore, we prove that atorvastatin could delay the procession of atherosclerosis and improve the stability of atherosclerotic plaques. Interestingly, we report that inhibition of GARP distinctly inhibits the anti-inflammatory effects of atorvastatin. We conclude that atorvastatin improves the inflammatory response in atherosclerosis partly by upregulating the expression of GARP on regulatory T cells. PMID:26063978

Polymicrobial Oral Infection with Four Periodontal Bacteria Orchestrates a Distinct Inflammatory Response and Atherosclerosis in ApoE null Mice.

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Chukkapalli, Sasanka S; Velsko, Irina M; Rivera-Kweh, Mercedes F; Zheng, Donghang; Lucas, Alexandra R; Kesavalu, Lakshmyya

2015-01-01

Periodontal disease (PD) develops from a synergy of complex subgingival oral microbiome, and is linked to systemic inflammatory atherosclerotic vascular disease (ASVD). To investigate how a polybacterial microbiome infection influences atherosclerotic plaque progression, we infected the oral cavity of ApoE null mice with a polybacterial consortium of 4 well-characterized periodontal pathogens, Porphyromonas gingivalis, Treponema denticola, Tannerealla forsythia and Fusobacterium nucleatum, that have been identified in human atherosclerotic plaque by DNA screening. We assessed periodontal disease characteristics, hematogenous dissemination of bacteria, peripheral T cell response, serum inflammatory cytokines, atherosclerosis risk factors, atherosclerotic plaque development, and alteration of aortic gene expression. Polybacterial infections have established gingival colonization in ApoE null hyperlipidemic mice and displayed invasive characteristics with hematogenous dissemination into cardiovascular tissues such as the heart and aorta. Polybacterial infection induced significantly higher levels of serum risk factors oxidized LDL (p Periodontal microbiome infection is associated with significant decreases in Apoa1, Apob, Birc3, Fga, FgB genes that are associated with atherosclerosis. Periodontal infection for 12 weeks had modified levels of inflammatory molecules, with decreased Fas ligand, IL-13, SDF-1 and increased chemokine RANTES. In contrast, 24 weeks of infection induced new changes in other inflammatory molecules with reduced KC, MCSF, enhancing GM-CSF, IFNγ, IL-1β, IL-13, IL-4, IL-13, lymphotactin, RANTES, and also an increase in select inflammatory molecules. This study demonstrates unique differences in the host immune response to a polybacterial periodontal infection with atherosclerotic lesion progression in a mouse model.

Deficiency of ATP-binding cassette transporters A1 and G1 in macrophages increases inflammation and accelerates atherosclerosis in mice.

Science.gov (United States)

Westerterp, Marit; Murphy, Andrew J; Wang, Mi; Pagler, Tamara A; Vengrenyuk, Yuliya; Kappus, Mojdeh S; Gorman, Darren J; Nagareddy, Prabhakara R; Zhu, Xuewei; Abramowicz, Sandra; Parks, John S; Welch, Carrie; Fisher, Edward A; Wang, Nan; Yvan-Charvet, Laurent; Tall, Alan R

2013-05-24

Plasma high-density lipoprotein levels are inversely correlated with atherosclerosis. Although it is widely assumed that this is attributable to the ability of high-density lipoprotein to promote cholesterol efflux from macrophage foam cells, direct experimental support for this hypothesis is lacking. To assess the role of macrophage cholesterol efflux pathways in atherogenesis. We developed mice with efficient deletion of the ATP-binding cassette transporters A1 and G1 (ABCA1 and ABCG1) in macrophages (MAC-ABC(DKO) mice) but not in hematopoietic stem or progenitor populations. MAC-ABC(DKO) bone marrow (BM) was transplanted into Ldlr(-/-) recipients. On the chow diet, these mice had similar plasma cholesterol and blood monocyte levels but increased atherosclerosis compared with controls. On the Western-type diet, MAC-ABC(DKO) BM-transplanted Ldlr(-/-) mice had disproportionate atherosclerosis, considering they also had lower very low-density lipoprotein/low-density lipoprotein cholesterol levels than controls. ABCA1/G1-deficient macrophages in lesions showed increased inflammatory gene expression. Unexpectedly, Western-type diet-fed MAC-ABC(DKO) BM-transplanted Ldlr(-/-) mice displayed monocytosis and neutrophilia in the absence of hematopoietic stem and multipotential progenitor cells proliferation. Mechanistic studies revealed increased expressions of machrophage colony stimulating factor and granulocyte colony stimulating factor in splenic macrophage foam cells, driving BM monocyte and neutrophil production. These studies show that macrophage deficiency of ABCA1/G1 is proatherogenic likely by promoting plaque inflammation and uncover a novel positive feedback loop in which cholesterol-laden splenic macrophages signal BM progenitors to produce monocytes, with suppression by macrophage cholesterol efflux pathways.

Long Term Follow Up of Celiac Disease—Is Atherosclerosis a Problem?

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Anna Rybak

2014-07-01

Full Text Available Celiac disease (CD is a lifelong condition and it often involves impaired nutrition, wide spectrum of symptoms and it requires constant dietetic treatment. The impact of the gluten-free diet on patients’ nutritional status and on the other biochemical parameters is being widely investigated. In this article we looked into particular risk factors that might lead to increased prevalence of atherosclerosis in CD patients, including nutritional status, gluten-free diet, lipids profile and concomitant disease—type 1 diabetes mellitus. Here, we present the current data and research on these risk factors of atherosclerosis with respect to celiac disease.

Short-term changes in arterial inflammation predict long-term changes in atherosclerosis progression

Energy Technology Data Exchange (ETDEWEB)

Joseph, Philip [Massachusetts General Hospital and Harvard Medical School, Cardiology Division and Cardiac MR PET CT Program, Boston, MA (United States); McMaster University, Population Health Research Institute, Department of Medicine, and Department of Radiology, Hamilton, ON (Canada); Ishai, Amorina; Tawakol, Ahmed [Massachusetts General Hospital and Harvard Medical School, Cardiology Division and Cardiac MR PET CT Program, Boston, MA (United States); Mani, Venkatesh [Icahn School of Medicine at Mount Sinai School of Medicine, Translational and Molecular Imaging Institute and Department of Radiology, New York, NY (United States); Kallend, David [The Medicines Company, Parsippany, NJ (United States); Rudd, James H.F. [University of Cambridge, Division of Cardiovascular Medicine, Cambridge (United Kingdom); Fayad, Zahi A. [Icahn School of Medicine at Mount Sinai School of Medicine, Translational and Molecular Imaging Institute and Department of Radiology, New York, NY (United States); Icahn School of Medicine at Mount Sinai School of Medicine, Hess CSM Building Floor TMII, Rm S1-104, Translational and Molecular Imaging Institute and Department of Radiology, New York, NY (United States)

2017-01-15

It remains unclear whether changes in arterial wall inflammation are associated with subsequent changes in the rate of structural progression of atherosclerosis. In this sub-study of the dal-PLAQUE clinical trial, multi-modal imaging was performed using 18-fludeoxyglucose (FDG) positron emission tomography (PET, at 0 and 6 months) and magnetic resonance imaging (MRI, at 0 and 24 months). The primary objective was to determine whether increasing FDG uptake at 6 months predicted atherosclerosis progression on MRI at 2 years. Arterial inflammation was measured by the carotid FDG target-to-background ratio (TBR), and atherosclerotic plaque progression was defined as the percentage change in carotid mean wall area (MWA) and mean wall thickness (MWT) on MRI between baseline and 24 months. A total of 42 participants were included in this sub-study. The mean age of the population was 62.5 years, and 12 (28.6 %) were women. In participants with (vs. without) any increase in arterial inflammation over 6 months, the long-term changes in both MWT (% change MWT: 17.49 % vs. 1.74 %, p = 0.038) and MWA (% change MWA: 25.50 % vs. 3.59 %, p = 0.027) were significantly greater. Results remained significant after adjusting for clinical and biochemical covariates. Individuals with no increase in arterial inflammation over 6 months had no significant structural progression of atherosclerosis over 24 months as measured by MWT (p = 0.616) or MWA (p = 0.373). Short-term changes in arterial inflammation are associated with long-term structural atherosclerosis progression. These data support the concept that therapies that reduce arterial inflammation may attenuate or halt progression of atherosclerosis. (orig.)

Short-term changes in arterial inflammation predict long-term changes in atherosclerosis progression

International Nuclear Information System (INIS)

Joseph, Philip; Ishai, Amorina; Tawakol, Ahmed; Mani, Venkatesh; Kallend, David; Rudd, James H.F.; Fayad, Zahi A.

2017-01-01

It remains unclear whether changes in arterial wall inflammation are associated with subsequent changes in the rate of structural progression of atherosclerosis. In this sub-study of the dal-PLAQUE clinical trial, multi-modal imaging was performed using 18-fludeoxyglucose (FDG) positron emission tomography (PET, at 0 and 6 months) and magnetic resonance imaging (MRI, at 0 and 24 months). The primary objective was to determine whether increasing FDG uptake at 6 months predicted atherosclerosis progression on MRI at 2 years. Arterial inflammation was measured by the carotid FDG target-to-background ratio (TBR), and atherosclerotic plaque progression was defined as the percentage change in carotid mean wall area (MWA) and mean wall thickness (MWT) on MRI between baseline and 24 months. A total of 42 participants were included in this sub-study. The mean age of the population was 62.5 years, and 12 (28.6 %) were women. In participants with (vs. without) any increase in arterial inflammation over 6 months, the long-term changes in both MWT (% change MWT: 17.49 % vs. 1.74 %, p = 0.038) and MWA (% change MWA: 25.50 % vs. 3.59 %, p = 0.027) were significantly greater. Results remained significant after adjusting for clinical and biochemical covariates. Individuals with no increase in arterial inflammation over 6 months had no significant structural progression of atherosclerosis over 24 months as measured by MWT (p = 0.616) or MWA (p = 0.373). Short-term changes in arterial inflammation are associated with long-term structural atherosclerosis progression. These data support the concept that therapies that reduce arterial inflammation may attenuate or halt progression of atherosclerosis. (orig.)

Atherosclerosis and liver inflammation induced by increased dietary cholesterol intake: A combined transcriptomics and metabolomics analysis

NARCIS (Netherlands)

Kleemann, R.; Verschuren, L.; Erk, M.J. van; Nikolsky, Y.; Cnubben, N.H.P.; Verheij, E.R.; Smilde, A.K.; Hendriks, H.F.J.; Zadelaar, A.S.M.; Smith, G.J.; Kaznacheev, V.; Nikolskaya, T.; Melnikov, A.; Hurt-Camejo, E.; Greef, J. van der; Ommen, B. van; Kooistra, T.

2007-01-01

Background: Increased dietary cholesterol intake is associated with atherosclerosis. Atherosclerosis development requires a lipid and an inflammatory component. It is unclear where and how the inflammatory component develops. To assess the role of the liver in the evolution of inflammation, we

Efficacy of bioactive compounds from extra virgin olive oil to modulate atherosclerosis development.

Science.gov (United States)

Lou-Bonafonte, José M; Arnal, Carmen; Navarro, María A; Osada, Jesús

2012-07-01

As olive oil is the main source of calories in the Mediterranean diet, a great deal of research has been devoted to characterizing its role in atherosclerosis. Virgin olive oil is an oily matrix that contains hydrocarbons, mainly squalene; triterpenes such as uvaol, erythrodiol, oleanolic, and maslinic acid; phytosterols; and a wide range of phenolic compounds comprising simple phenols, flavonoids, secoiridoids, and lignans. In this review, we analyze the studies dealing with atherosclerosis and olive oil in several species. A protective role of virgin olive oil against atherosclerosis has been shown in ApoE-deficient mice and hamsters. In the former animal, sex, dose, and dietary cholesterol are modulators of the outcome. Contradictory findings have been reported for rabbits, a circumstance that could be due to the profusion of experimental designs, differing in terms of doses and animal strains, as well as sources of olive oils. This role has yet to be fully validated in humans. Minor components of olive oil have been shown to be involved in atherosclerosis protection. Nevertheless, evidence of the potential of isolated compounds or the right combination of them to achieve the antiatherosclerotic effect of virgin olive oil is inconclusive and will undoubtedly require further experimental support. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Atherosclerosis risk factors in pigeon squabs

International Nuclear Information System (INIS)

Klumpp, S.A.; Clarkson, T.B.

1986-01-01

The basis for atherosclerosis susceptibility of White Carneau (WC) and resistance of Show Racer (SR) pigeons is not known. Body weight (BW), total serum cholesterol (TSC), growth of the aorta and replication of endothelial cells of the distal thoracic aorta (lesion prone site) of 1, 2 and 4 week old squabs were studied. Aortic measurements were determined morphometrically, and endothelial cell replication was quantitated by 24-hour 3 H-thymidine labeling and whole-mount SEM autoradiography. From hatching to 4 weeks, BW increased more in WC than SR (22 to 473 gm in WC vs 19 to 416 gm in SR, p 2 ) in WC and 44% (101, 140 and 146 mm 2 ) in SR. Aortic surface area was significantly larger (0 = 0.002) in the 4 week WC than 4 week SR. 3 H-thymidine labeled endothelial cells at 1, 2 and 4 weeks were 783, 387 and 53 in WC and 674, 283 and 27 cells/mm 2 in SR. Endothelial replication in the 4 week WC was twice that of the SR and significantly different between breeds at 2 and 4 weeks (p = 0.04; p = 0.02, respectively). Higher TSC, endothelial cell replication and larger aortic surface area in the WC may be contributing factors to increased atherosclerosis susceptibility

Histomorphological features of atherosclerosis in the left anterior ...

African Journals Online (AJOL)

The pattern of coronary artery atherosclerosis is valuable in informing mitigation strategies for coronary heart disease. Histomorphological data on this disease among Africans living in Sub Saharan Africa are, however, scarce. The left anterior descending is one of the most commonly afflicted arteries. This study, therefore ...

Atherosclerosis and Nutrition with Special Reference to Populations ...

African Journals Online (AJOL)

Severe atherosclerosis and its sequelae-coronary heart disease, cerebral vascular disease, and peripheral vascular disease-share major responsibility for half the mortality rate in affluent Western populations. In Africa, particularly South Africa, a study of the extent and severity of lesions is particularly interesting because of ...

Gene-based testing of interactions in association studies of quantitative traits.

Directory of Open Access Journals (Sweden)

Li Ma

Full Text Available Various methods have been developed for identifying gene-gene interactions in genome-wide association studies (GWAS. However, most methods focus on individual markers as the testing unit, and the large number of such tests drastically erodes statistical power. In this study, we propose novel interaction tests of quantitative traits that are gene-based and that confer advantage in both statistical power and biological interpretation. The framework of gene-based gene-gene interaction (GGG tests combine marker-based interaction tests between all pairs of markers in two genes to produce a gene-level test for interaction between the two. The tests are based on an analytical formula we derive for the correlation between marker-based interaction tests due to linkage disequilibrium. We propose four GGG tests that extend the following P value combining methods: minimum P value, extended Simes procedure, truncated tail strength, and truncated P value product. Extensive simulations point to correct type I error rates of all tests and show that the two truncated tests are more powerful than the other tests in cases of markers involved in the underlying interaction not being directly genotyped and in cases of multiple underlying interactions. We applied our tests to pairs of genes that exhibit a protein-protein interaction to test for gene-level interactions underlying lipid levels using genotype data from the Atherosclerosis Risk in Communities study. We identified five novel interactions that are not evident from marker-based interaction testing and successfully replicated one of these interactions, between SMAD3 and NEDD9, in an independent sample from the Multi-Ethnic Study of Atherosclerosis. We conclude that our GGG tests show improved power to identify gene-level interactions in existing, as well as emerging, association studies.

Hypercholesterolemia Tunes Hematopoietic Stem/Progenitor Cells for Inflammation and Atherosclerosis.

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Ma, Xiaojuan; Feng, Yingmei

2016-07-19

As the pathological basis of cardiovascular disease (CVD), atherosclerosis is featured as a chronic inflammation. Hypercholesterolemia is an independent risk factor for CVD. Accumulated studies have shown that hypercholesterolemia is associated with myeloid cell expansion, which stimulates innate and adaptive immune responses, strengthens inflammation, and accelerates atherosclerosis progression. Hematopoietic stem/progenitor cells (HSPC) in bone marrow (BM) expresses a panel of lipoprotein receptors to control cholesterol homeostasis. Deficiency of these receptors abrogates cellular cholesterol efflux, resulting in HSPC proliferation and differentiation in hypercholesterolemic mice. Reduction of the cholesterol level in the lipid rafts by infusion of reconstituted high-density lipoprotein (HDL) or its major apolipoprotein, apoA-I, reverses hypercholesterolemia-induced HSPC expansion. Apart from impaired cholesterol metabolism, inhibition of reactive oxygen species production suppresses HSPC activation and leukocytosis. These data indicate that the mechanisms underlying the effects of hypercholesterolemia on HSPC proliferation and differentiation could be multifaceted. Furthermore, dyslipidemia also regulates HSPC-neighboring cells, resulting in HSPC mobilization. In the article, we review how hypercholesterolemia evokes HSPC activation and mobilization directly or via its modification of BM microenvironment. We hope this review will bring light to finding key molecules to control HSPC expansion, inflammation, and atherosclerosis for the treatment of CVD.

Prediabetes is not a risk factor for subclinical coronary atherosclerosis.

Science.gov (United States)

Park, Gyung-Min; Cho, Young-Rak; Lee, Seung-Whan; Yun, Sung-Cheol; Won, Ki-Bum; Ann, Soe Hee; Kim, Yong-Giun; Kim, Shin-Jae; Roh, Jae-Hyung; Kim, Young-Hak; Yang, Dong Hyun; Kang, Joon-Won; Lim, Tae-Hwan; Jung, Chang Hee; Koh, Eun Hee; Lee, Woo Je; Kim, Min-Seon; Lee, Ki-Up; Park, Joong-Yeol; Kim, Hong-Kyu; Choe, Jaewon; Lee, Sang-Gon

2017-09-15

There are limited data regarding the influence of glycemic status on the risk of subclinical coronary atherosclerosis on coronary computed tomographic angiography (CCTA) in asymptomatic individuals. We analyzed 6434 asymptomatic individuals who underwent CCTA. The degree and extent of subclinical coronary atherosclerosis were assessed by CCTA, and ≥50% diameter stenosis was defined as significant. Of study participants, 2197 (34.1%), 3122 (48.5%), and 1115 (17.3%) were categorized as normal, prediabetic and diabetic individuals, respectively. Compared with normal individuals, there were no statistically differences in the adjusted odds ratios of prediabetic individuals for significant coronary artery stenosis (0.98, 95% confidence interval [CI] 0.80-1.22, p=0.888), any plaque (0.96, 95% CI 0.86-1.07, p=0.483), calcified plaque (0.90, 95% CI 0.79-1.01, p=0.080), non-calcified plaque (1.02, 95% CI 0.88-1.17, p=0.803), and mixed plaque (1.00, 95% CI 0.82-1.22, p=0.983). However, adjusted odds ratios for significant coronary artery stenosis (1.71, 95% CI 1.34-2.19, pprediabetic individuals were not associated with an increased risk of subclinical coronary atherosclerosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Aligning the systems of environmental accounting: From EU to Stockholm and vice versa

Energy Technology Data Exchange (ETDEWEB)

Burstroem, F.; Frostell, B. [Royal Inst. of Technology, Stockholm (Sweden). Dept. of Environmental Technology and Work Science

2001-07-01

During the last decade, authorities in local and regional communities, nations and international governance organisations, like the European Union (EU), have developed several systems for environmental accounting. An important issue in this development is the collection and collation of data. Except for the question of what data to collect, there is also a question of how to collect data. Focusing in particular on developments of physical environmental accounting systems in Sweden, a member nation of the EU, and drawing from experiences from work with materials accounting in the City of Stockholm, this paper discusses the need to align environmental accounting systems of different societal levels. It is argued that the systems of collecting 'environmental' data have to be better aligned with the objectives and strategies of environmental management and policy making, taking into account all aspects of utilisation of the basic data to be collected. If not, the result will be a conservation of the fragmented point solutions of environmental accounting systems we face today, resulting in inconsistency of data, duplication of data collection and processing efforts, and inflexibility to deal with changes. From this, it is also argued that the collection of data for physical environmental accounting (i.e. data on flows and stocks of materials and substances in society and the environment), would preferably be performed by a local/regional authority, but co-ordinated by national authorities and a national statistical office, under supervision of international authorities and statistical offices. Finally, the paper presents a structural framework for regional materials accounting, which combines a product-oriented strand with a substance-oriented strand of materials accounting, and allows for accounting and analysis on different levels of aggregation. This framework, which has been developed in co-operation with the City of Stockholm, should mainly be considered

Regional development via high-speed rail : A study of the Stockholm-Mälaren region and possibilities for Melbourne-regional Victoria

OpenAIRE

Bayley, Michael

2012-01-01

The purpose of this thesis is to examine, based on a study of the regional high-speed corridors in the Stockholm-Mälaren Region, the possibilities for regional high-speed rail in Melbourne-regional Victoria (Australia) to improve accessibility, and achieve regional development and balanced growth between the capital and its surrounding regions. It deals with the concept of 'regional' high-speed rail, a variant of classic high-speed rail that serves centres along regional corridors stemming fr...

Discussing compliance. Summary report from discussions with Robert Bernero and Chris Whipple regarding compliance with the Swedish HLW Regulations from meetings in Stockholm May 3 and 4, 1999

Energy Technology Data Exchange (ETDEWEB)

Jensen, Mikael

1999-06-01

Summary report from discussions with Robert Bernero and Chris Whipple regarding compliance with the Swedish HLW Regulations from meetings in Stockholm. The report also contains bibliographical information and preliminary observations made by Robert Bernero and Chris Whipple.

Discussing compliance. Summary report from discussions with Robert Bernero and Chris Whipple regarding compliance with the Swedish HLW Regulations from meetings in Stockholm May 3 and 4, 1999

International Nuclear Information System (INIS)

Jensen, Mikael

1999-06-01

Summary report from discussions with Robert Bernero and Chris Whipple regarding compliance with the Swedish HLW Regulations from meetings in Stockholm. The report also contains bibliographical information and preliminary observations made by Robert Bernero and Chris Whipple

Baldness and myocardial infarction in men: the atherosclerosis risk in communities study.

Science.gov (United States)

Shahar, Eyal; Heiss, Gerardo; Rosamond, Wayne D; Szklo, Moyses

2008-03-15

Because hair loss may be a surrogate measure of androgenic activity-possibly a determinant of coronary atherosclerosis-several studies have explored the presence and magnitude of an association between male pattern baldness and myocardial infarction (MI). In particular, vertex baldness, but not frontal baldness alone, was strongly associated with incident MI in a large, hospital-based, case-control study. The authors examined these associations in a cross-sectional sample of 5,056 men aged 52-75 years, of whom 767 had a history of MI. The sample was derived from the Atherosclerosis Risk in Communities (ARIC) Study (1987-1998). As compared with a baldness-free reference group, the estimated odds ratios for prevalent MI from a multivariable model were 1.28 (frontal baldness), 1.02 (mild vertex baldness), 1.40 (moderate vertex baldness), and 1.18 (severe vertex baldness). Other regression models have yielded similar results, including the absence of a monotonic "dose-response relation" between the extent of vertex baldness and prevalent MI. The authors also examined the relation of baldness pattern to carotid intimal-medial thickness, a measure of atherosclerosis, among those who were free of clinical cardiovascular disease. The estimated mean differences in carotid intimal-medial thickness between groups of men with various types of baldness and their baldness-free counterparts were all close to zero. The results of this study suggest that male pattern baldness is not a surrogate measure of an important risk factor for myocardial infarction or asymptomatic atherosclerosis.

Citrullus lanatus `Sentinel' (Watermelon) Extract Reduces Atherosclerosis in LDL Receptor Deficient Mice

Science.gov (United States)

Poduri, Aruna; Rateri, Debra L.; Saha, Shubin K.; Saha, Sibu; Daugherty, Alan

2012-01-01

Watermelon (Citrullus lanatus or C. lanatus) has many potentially bioactive compounds including citrulline, which may influence atherosclerosis. In this study, we determined the effects of C. lanatus, provided as an extract of the cultivar `sentinel', on hypercholesterolemia-induced atherosclerosis in mice. Male LDL receptor deficient mice at 8 weeks old were given either C. lanatus `sentinel' extract (2% vol/vol; n=10) or a mixture of matching carbohydrates (2% vol/vol; n=8) as the control in drinking water, while fed a saturated fat-enriched diet for 12 weeks ad libitum. Mice consuming C. lanatus `sentinel' extract had significantly increased plasma citrulline concentrations. Systolic blood pressure was comparable between the two groups. Consumption of C. lanatus `sentinel' extract led to lower body weight and fat mass without influencing lean mass. There were no differences in food and water intake, and urine output between the two groups. C. lanatus `sentinel' extract administration decreased plasma cholesterol concentrations that were attributed to reductions of intermediate/low density lipoprotein cholesterol. Plasma concentrations of MCP-1 and IFN-γ were decreased and IL-10 increased in mice consuming C. lanatus `sentinel' extract. Intake of C. lanatus `sentinel' extract resulted in reductions of atherosclerosis in both aortic arch and thoracic regions. In conclusion, consumption of C. lanatus `sentinel' extract led to reduced body weight gain, decreased plasma cholesterol concentrations, improved homeostasis of pro- and anti-inflammatory cytokines, and attenuated development of atherosclerosis without affecting systolic blood pressure in hypercholesterolemic mice. PMID:22902326

Enhanced susceptibility of low-density lipoproteins to oxidation in coronary bypass patients with progression of atherosclerosis

NARCIS (Netherlands)

Rijke, Y.B. de; Verwey, H.F.; Vogelezang, C.J.M.; Velde, E.A. van der; Princen, H.M.G.; Laarse, A. van der; Bruschke, A.V.G.; Berkel, T.J.C. van

1995-01-01

Oxidation of low-density lipoprotein (LDL) may play a causal role in atherosclerosis. In this study we analyzed whether the severity of progression of coronary atherosclerosis is related to the susceptibility of LDL to oxidative modification. On the basis of repeated coronary angiography, 28

The Biology of Atherosclerosis: General Paradigms and Distinct Pathogenic Mechanisms Among HIV-Infected Patients

OpenAIRE

Lo, Janet; Plutzky, Jorge

2012-01-01

Complications of atherosclerosis, including myocardial infarction and stroke, are the leading cause of death and disability worldwide. Recent data strongly implicate cardiovascular death as a contributor to mortality among patients with human immunodeficiency virus (HIV) infection, with evidence suggesting increased incidence of atherosclerosis among these patients. Therefore, greater understanding of atherosclerotic mechanisms and how these responses may be similar or distinct in HIV-infecte...

An alternative method for quantifying coronary artery calcification: the multi-ethnic study of atherosclerosis (MESA).

Science.gov (United States)

Liang, C Jason; Budoff, Matthew J; Kaufman, Joel D; Kronmal, Richard A; Brown, Elizabeth R

2012-07-02

Extent of atherosclerosis measured by amount of coronary artery calcium (CAC) in computed tomography (CT) has been traditionally assessed using thresholded scoring methods, such as the Agatston score (AS). These thresholded scores have value in clinical prediction, but important information might exist below the threshold, which would have important advantages for understanding genetic, environmental, and other risk factors in atherosclerosis. We developed a semi-automated threshold-free scoring method, the spatially weighted calcium score (SWCS) for CAC in the Multi-Ethnic Study of Atherosclerosis (MESA). Chest CT scans were obtained from 6814 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). The SWCS and the AS were calculated for each of the scans. Cox proportional hazards models and linear regression models were used to evaluate the associations of the scores with CHD events and CHD risk factors. CHD risk factors were summarized using a linear predictor. Among all participants and participants with AS > 0, the SWCS and AS both showed similar strongly significant associations with CHD events (hazard ratios, 1.23 and 1.19 per doubling of SWCS and AS; 95% CI, 1.16 to 1.30 and 1.14 to 1.26) and CHD risk factors (slopes, 0.178 and 0.164; 95% CI, 0.162 to 0.195 and 0.149 to 0.179). Even among participants with AS = 0, an increase in the SWCS was still significantly associated with established CHD risk factors (slope, 0.181; 95% CI, 0.138 to 0.224). The SWCS appeared to be predictive of CHD events even in participants with AS = 0, though those events were rare as expected. The SWCS provides a valid, continuous measure of CAC suitable for quantifying the extent of atherosclerosis without a threshold, which will be useful for examining novel genetic and environmental risk factors for atherosclerosis.

An alternative method for quantifying coronary artery calcification: the multi-ethnic study of atherosclerosis (MESA

Directory of Open Access Journals (Sweden)

Liang C

2012-07-01

Full Text Available Abstract Background Extent of atherosclerosis measured by amount of coronary artery calcium (CAC in computed tomography (CT has been traditionally assessed using thresholded scoring methods, such as the Agatston score (AS. These thresholded scores have value in clinical prediction, but important information might exist below the threshold, which would have important advantages for understanding genetic, environmental, and other risk factors in atherosclerosis. We developed a semi-automated threshold-free scoring method, the spatially weighted calcium score (SWCS for CAC in the Multi-Ethnic Study of Atherosclerosis (MESA. Methods Chest CT scans were obtained from 6814 participants in the Multi-Ethnic Study of Atherosclerosis (MESA. The SWCS and the AS were calculated for each of the scans. Cox proportional hazards models and linear regression models were used to evaluate the associations of the scores with CHD events and CHD risk factors. CHD risk factors were summarized using a linear predictor. Results Among all participants and participants with AS > 0, the SWCS and AS both showed similar strongly significant associations with CHD events (hazard ratios, 1.23 and 1.19 per doubling of SWCS and AS; 95% CI, 1.16 to 1.30 and 1.14 to 1.26 and CHD risk factors (slopes, 0.178 and 0.164; 95% CI, 0.162 to 0.195 and 0.149 to 0.179. Even among participants with AS = 0, an increase in the SWCS was still significantly associated with established CHD risk factors (slope, 0.181; 95% CI, 0.138 to 0.224. The SWCS appeared to be predictive of CHD events even in participants with AS = 0, though those events were rare as expected. Conclusions The SWCS provides a valid, continuous measure of CAC suitable for quantifying the extent of atherosclerosis without a threshold, which will be useful for examining novel genetic and environmental risk factors for atherosclerosis.

Is the Use of Fullerene in Photodynamic Therapy Effective for Atherosclerosis?

International Nuclear Information System (INIS)

Nitta, Norihisa; Seko, Ayumi; Sonoda, Akinaga; Ohta, Shinichi; Tanaka, Toyohiko; Takahashi, Masashi; Murata, Kiyoshi; Takemura, Shizuki; Sakamoto, Tsutomu; Tabata, Yasuhiko

2008-01-01

The purpose of this study was to evaluate Fullerene as a therapeutic photosensitizer in the treatment of atherosclerosis. An atherosclerotic experimental rabbit model was prepared by causing intimal injury to bilateral external iliac arteries using balloon expansion. In four atherosclerotic rabbits and one normal rabbit, polyethylene glycol-modified Fullerene (Fullerene-PEG) was infused into the left external iliac artery and illuminated by light emitting diode (LED), while the right external iliac artery was only illuminated by LED. Two weeks later, the histological findings for each iliac artery were evaluated quantitatively and comparisons were made among atherosclerotic Fullerene+LED artery (n = 4), atherosclerotic light artery (n = 4), normal Fullerene+LED artery (n = 1), and normal light artery (n = 1). An additional two atherosclerotic rabbits were studied by fluorescence microscopy, after Fullerene-PEG-Cy5 complex infusion into the left external iliac artery, for evaluation of Fullerene-PEG incorporated within the atherosclerotic lesions. The degree of atherosclerosis in the atherosclerotic Fullerene+LED artery was significantly (p < 0.05) more severe than that in the atherosclerotic LED artery. No pathological change was observed in normal Fullerene+LED and LED arteries. In addition, strong accumulation of Fullerene-PEG-Cy5 complex within the plaque of the left iliac artery of the two rabbits was demonstrated, in contrast to no accumulation in the right iliac artery. We conclude that infusion of a high concentration of Fullerene-PEG followed by photo-illumination resulted not in a suppression of atherosclerosis but in a progression of atherosclerosis in experimental rabbit models. However, this intervention showed no adverse effects on the normal iliac artery

Activation of Liver X Receptor Decreases Atherosclerosis in Ldlr−/− mice in the Absence of ABCA1 and ABCG1 in Myeloid Cells

Science.gov (United States)

Kappus, Mojdeh S.; Murphy, Andrew J.; Abramowicz, Sandra; Ntonga, Vusisizwe; Welch, Carrie L.; Tall, Alan R.; Westerterp, Marit

2014-01-01

Objective Liver X Receptor (LXR) activators decrease atherosclerosis in mice. LXR activators (1) directly up-regulate genes involved in reverse cholesterol transport (RCT) and (2) exert anti-inflammatory effects mediated by transrepression of NFκB target genes. We investigated whether myeloid cell deficiency of ATP-binding cassette transporters A1 and G1 (ABCA1/G1), principal targets of LXR that promote macrophage cholesterol efflux and initiate RCT, would abolish the beneficial effects of LXR activation on atherosclerosis. Approach and Results LXR activator T0901317 (T0) substantially reduced inflammatory gene expression in macrophages lacking ABCA1/G1. Ldlr−/− mice were transplanted with Abca1−/−Abcg1−/− or wild-type bone marrow (BM) and fed a Western-type diet (WTD) for 6 weeks with or without T0 supplementation. Abca1/g1 BM deficiency increased atherosclerotic lesion complexity and inflammatory cell infiltration into the adventitia and myocardium. T0 markedly decreased lesion area, complexity and inflammatory cell infiltration in the Abca1−/−Abcg1−/− BM transplanted mice. To investigate whether this was due to macrophage Abca1/g1 deficiency, Ldlr−/− mice were transplanted with LysmCreAbca1fl/flAbcg1fl/fl or Abca1fl/flAbcg1fl/fl BM and fed WTD with or without the more specific LXR agonist GW3965 for 12 weeks. GW3965 decreased lesion size in both groups and the decrease was more prominent in the LysmCreAbca1fl/flAbcg1fl/fl group. Conclusions The results suggest that anti-inflammatory effects of LXR activators are of key importance to their anti-atherosclerotic effects in vivo independent of cholesterol efflux pathways mediated by macrophage ABCA1/G1. This has implications for the development of LXR activators that lack adverse effects on lipogenic genes while maintaining the ability to trans-repress inflammatory genes. PMID:24311381

[Potential protective role of nitric oxide and Hsp70 linked to functional foods in the atherosclerosis].

Science.gov (United States)

Camargo, Alejandra B; Manucha, Walter

Atherosclerosis, one of the main pathologic entities considered epidemic and a worldwide public health problem, is currently under constant review as regards its basic determining mechanisms and therapeutic possibilities. In this regard, all patients afflicted with the disease exhibit mitochondrial dysfunction, oxidative stress and inflammation. Interestingly, nitric oxide - a known vasoactive messenger gas - has been closely related to the inflammatory, oxidative and mitochondrial dysfunctional process that characterizes atherosclerosis. In addition, it has recently been demonstrated that alterations in the bioavailability of nitric oxide would induce the expression of heat shock proteins. This agrees with the use of functional foods as a strategy to prevent both vascular aging and the development of atherosclerosis. Finally, a greater knowledge regarding the mechanisms implied in the development of atherosclerosis will enable proposing new and possible hygiene, health and therapeutic interventions. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

IGF-1 Has Plaque-Stabilizing Effects in Atherosclerosis by Altering Vascular Smooth Muscle Cell Phenotype

Science.gov (United States)

von der Thüsen, Jan H.; Borensztajn, Keren S.; Moimas, Silvia; van Heiningen, Sandra; Teeling, Peter; van Berkel, Theo J.C.; Biessen, Erik A.L.

2011-01-01

Insulin-like growth factor-1 (IGF-1) signaling is important for the maintenance of plaque stability in atherosclerosis due to its effects on vascular smooth muscle cell (vSMC) phenotype. To investigate this hypothesis, we studied the effects of the highly inflammatory milieu of the atherosclerotic plaque on IGF-1 signaling and stability-related phenotypic parameters of murine vSMCs in vitro, and the effects of IGF-1 supplementation on plaque phenotype in an atherosclerotic mouse model. M1-polarized, macrophage-conditioned medium inhibited IGF-1 signaling by ablating IGF-1 and increasing IGF-binding protein 3, increased vSMC apoptosis, and decreased proliferation. Expression of α-actin and col3a1 genes was strongly attenuated by macrophage-conditioned medium, whereas expression of matrix-degrading enzymes was increased. Importantly, all of these effects could be corrected by supplementation with IGF-1. In vivo, treatment with the stable IGF-1 analog Long R3 IGF-1 in apolipoprotein E knockout mice reduced stenosis and core size, and doubled cap/core ratio in early atherosclerosis. In advanced plaques, Long R3 IGF-1 increased the vSMC content of the plaque by more than twofold and significantly reduced the rate of intraplaque hemorrhage. We believe that IGF-1 in atherosclerotic plaques may have a role in preventing plaque instability, not only by modulating smooth muscle cell turnover, but also by altering smooth muscle cell phenotype. PMID:21281823

Lactobacillus reuteri prevents diet-induced obesity, but not atherosclerosis, in a strain dependent fashion in Apoe-/- mice.

Directory of Open Access Journals (Sweden)

Frida Fåk

Full Text Available OBJECTIVE: To investigate whether the specific strains of Lactobacillus reuteri modulates the metabolic syndrome in Apoe-/- mice. METHODS: 8 week-old Apoe-/- mice were subdivided into four groups who received either L. reuteri ATCC PTA 4659 (ATCC, DSM 17938 (DSM, L6798, or no bacterial supplement in the drinking water for 12 weeks. The mice were fed a high-fat Western diet with 0.2% cholesterol and body weights were monitored weekly. At the end of the study, oral glucose and insulin tolerance tests were conducted. In addition, adipose and liver weights were recorded along with analyses of mRNA expression of ileal Angiopoietin-like protein 4 (Angptl4, the macrophage marker F4/80 encoded by the gene Emr1 and liver Acetyl-CoA carboxylase 1 (Acc1, Fatty acid synthase (Fas and Carnitine palmitoyltransferase 1a (Cpt1a. Atherosclerosis was assessed in the aortic root region of the heart. RESULTS AND CONCLUSIONS: Mice receiving L. reuteri ATCC gained significantly less body weight than the control mice, whereas the L6798 mice gained significantly more. Adipose and liver weights were also reduced in the ATCC group. Serum insulin levels were lower in the ATCC group, but no significant effects were observed in the glucose or insulin tolerance tests. Lipogenic genes in the liver were not altered by any of the bacterial treatments, however, increased expression of Cpt1a was found in the ATCC group, indicating increased β-oxidation. Correspondingly, the liver trended towards having lower fat content. There were no effects on inflammatory markers, blood cholesterol or atherosclerosis. In conclusion, the probiotic L. reuteri strain ATCC PTA 4659 partly prevented diet-induced obesity, possibly via a previously unknown mechanism of inducing liver expression of Cpt1a.

Inflammatory markers and extent and progression of early atherosclerosis

DEFF Research Database (Denmark)

Willeit, Peter; Thompson, Simon G; Agewall, Stefan

2016-01-01

BACKGROUND: Large-scale epidemiological evidence on the role of inflammation in early atherosclerosis, assessed by carotid ultrasound, is lacking. We aimed to quantify cross-sectional and longitudinal associations of inflammatory markers with common-carotid-artery intima-media thickness (CCA-IMT)...

Periodontitis as a Risk Factor of Atherosclerosis

Directory of Open Access Journals (Sweden)

Jirina Bartova

2014-01-01

Full Text Available Over the last two decades, the amount of evidence corroborating an association between dental plaque bacteria and coronary diseases that develop as a result of atherosclerosis has increased. These findings have brought a new aspect to the etiology of the disease. There are several mechanisms by which dental plaque bacteria may initiate or worsen atherosclerotic processes: activation of innate immunity, bacteremia related to dental treatment, and direct involvement of mediators activated by dental plaque and involvement of cytokines and heat shock proteins from dental plaque bacteria. There are common predisposing factors which influence both periodontitis and atherosclerosis. Both diseases can be initiated in early childhood, although the first symptoms may not appear until adulthood. The formation of lipid stripes has been reported in 10-year-old children and the increased prevalence of obesity in children and adolescents is a risk factor contributing to lipid stripes development. Endothelium damage caused by the formation of lipid stripes in early childhood may lead to bacteria penetrating into blood circulation after oral cavity procedures for children as well as for patients with aggressive and chronic periodontitis.

A semantically-aided architecture for a web-based monitoring system for carotid atherosclerosis.

Science.gov (United States)

Kolias, Vassileios D; Stamou, Giorgos; Golemati, Spyretta; Stoitsis, Giannis; Gkekas, Christos D; Liapis, Christos D; Nikita, Konstantina S

2015-08-01

Carotid atherosclerosis is a multifactorial disease and its clinical diagnosis depends on the evaluation of heterogeneous clinical data, such as imaging exams, biochemical tests and the patient's clinical history. The lack of interoperability between Health Information Systems (HIS) does not allow the physicians to acquire all the necessary data for the diagnostic process. In this paper, a semantically-aided architecture is proposed for a web-based monitoring system for carotid atherosclerosis that is able to gather and unify heterogeneous data with the use of an ontology and to create a common interface for data access enhancing the interoperability of HIS. The architecture is based on an application ontology of carotid atherosclerosis that is used to (a) integrate heterogeneous data sources on the basis of semantic representation and ontological reasoning and (b) access the critical information using SPARQL query rewriting and ontology-based data access services. The architecture was tested over a carotid atherosclerosis dataset consisting of the imaging exams and the clinical profile of 233 patients, using a set of complex queries, constructed by the physicians. The proposed architecture was evaluated with respect to the complexity of the queries that the physicians could make and the retrieval speed. The proposed architecture gave promising results in terms of interoperability, data integration of heterogeneous sources with an ontological way and expanded capabilities of query and retrieval in HIS.

Incidence, aetiology and injury characteristics of traumatic spinal cord injury in Stockholm, Sweden: A prospective, population-based update.

Science.gov (United States)

Joseph, Conran; Andersson, Nina; Bjelak, Sapko; Giesecke, Kajsa; Hultling, Claes; Nilsson Wikmar, Lena; Phillips, Julie; Seiger, Åke; Stenimahitis, Vasilios; Trok, Katarzyna; Åkesson, Elisabet; Wahman, Kerstin

2017-05-16

To update the incidence rate, aetiology and injury characteristics of acutely-injured adults with traumatic spinal cord injury in Stockholm, Sweden, using international standards of reporting. Prospective, (regional) population-based observation. Forty-nine consecutively enrolled individuals. A surveillance system of newly-injured adults with traumatic spinal cord injury was implemented for an 18-month period. The International Spinal Cord Injury Core Data Set was used to collect data on those who survived the first 7 days post-injury. After an 18-month period, 49 incident cases were registered, of whom 45 were included in this study. The crude incidence rate was 19.0 per million, consisting mainly of men (60%), and the mean age of the cohort was 55 years (median 58). Causes of injury were almost exclusively limited to falls and transport-related events, accounting for 58% and 40% of cases, respectively. The incidence has remained stable when compared with the previous study; however, significant differences exist for injury aetiology (p = 0.004) and impairment level (p = 0.01) in that more fall- and transport-related spinal cord injury occurred, and a larger proportion of persons was left with resultant tetraplegia, in the current study, compared with more sport-related injuries and those left with paraplegia in the previous study. The incidence rate appeared to remain stable in Stockholm, Sweden. However, significant changes in injury aetiology and impairment-level post injury were found, compared with the previous study. There remains a need for developing fall-related prevention strategies in rehabilitation settings as well as in population-based programmes.

A Study of Carotid Intimomedial Thickness as a Primary Marker of Atherosclerosis in Patients with Rheumatoid Arthritis.

Directory of Open Access Journals (Sweden)

Shivani Patel

2016-01-01

RA is a chronic disease associatedd with chronic subclinical inflammation. In view of the consequentr high risk of atherosclerosis seen in these patients CIMT may serve as an early surrogate marker of atherosclerosis. We can identify these high risk subgroups of patients with a simple, reliable, inexpensive, and non-invasive bedside carotid Doppler sonogram even in resource poor countries such as India. In our view physicians should be vigilant to identify and screen regularly for atherosclerosis with CIMT in RA patients, so that prompt early management can prevent the cardiovascular complications.

Molecular imaging of inflammation in the ApoE -/- mouse model of atherosclerosis with IodoDPA

International Nuclear Information System (INIS)

Foss, Catherine A.; Bedja, Djahida; Mease, Ronnie C.; Wang, Haofan; Kass, David A.; Chatterjee, Subroto; Pomper, Martin G.

2015-01-01

Background: Atherosclerosis is a common and serious vascular disease predisposing individuals to myocardial infarction and stroke. Intravascular plaques, the pathologic lesions of atherosclerosis, are largely composed of cholesterol-laden luminal macrophage-rich infiltrates within a fibrous cap. The ability to detect those macrophages non-invasively within the aorta, carotid artery and other vessels would allow physicians to determine plaque burden, aiding management of patients with atherosclerosis. Methods and results: We previously developed a low-molecular-weight imaging agent, [ 125 I]iodo-DPA-713 (iodoDPA), which selectively targets macrophages. Here we use it to detect both intravascular macrophages and macrophage infiltrates within the myocardium in the ApoE -/- mouse model of atherosclerosis using single photon emission computed tomography (SPECT). SPECT data were confirmed by echocardiography, near-infrared fluorescence imaging and histology. SPECT images showed focal uptake of radiotracer at the aortic root in all ApoE -/- mice, while the age-matched controls were nearly devoid of radiotracer uptake. Focal radiotracer uptake along the descending aorta and within the myocardium was also observed in affected animals. Conclusions: IodoDPA is a promising new imaging agent for atherosclerosis, with specificity for the macrophage component of the lesions involved. - Highlights: • [ 125 I]iodoDPA SPECT detects atherosclerotic plaques in ApoE -/- mice with high contrast. • Plaques are detected in ApoE -/- mice regardless of diet with iodoDPA. • iodoDPA has very low uptake in healthy tissue including healthy TSPO + tissues at 24 h

Changes of lysosomes in the earliest stages of the development of atherosclerosis.

Science.gov (United States)

Bobryshev, Yuri V; Shchelkunova, Tatyana A; Morozov, Ivan A; Rubtsov, Petr M; Sobenin, Igor A; Orekhov, Alexander N; Smirnov, Alexander N

2013-05-01

One of hypotheses of atherosclerosis is based on a presumption that the zones prone to the development of atherosclerosis contain lysosomes which are characterized by enzyme deficiency and thus, are unable to dispose of lipoproteins. The present study was undertaken to investigate the characteristics and changes of lysosomes in the earliest stages of the development of atherosclerosis. Electron microscopic immunocytochemistry revealed that there were certain changes in the distribution of CD68 antigen in lysosomes along the 'normal intima-initial lesion-fatty streak' sequence. There were no significant changes found in the key mRNAs encoding for the components of endosome/lysosome compartment in initial atherosclerotic lesions, but in fatty streaks, the contents of EEA1 and Rab5a mRNAs were found to be diminished while the contents of CD68 and p62 mRNAs were increased, compared with the intact tissue. The study reinforces a view that changes occurring in lysosomes play a role in atherogenesis from the very earlier stages of the disease. © 2013 The Authors. Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Markers of insulin resistance and carotid atherosclerosis. A comparison of the homeostasis model assessment and triglyceride glucose index.

Science.gov (United States)

Irace, C; Carallo, C; Scavelli, F B; De Franceschi, M S; Esposito, T; Tripolino, C; Gnasso, A

2013-07-01

The present investigation was designed to test the association between carotid atherosclerosis and two simple markers of insulin resistance, i.e. HOMA-Index and TyG-Index. The study was performed in two different cohorts. In the first cohort, 330 individuals were enrolled. Blood pressure, lipids, glucose, waist and cigarette smoking were evaluated. HOMA-IR and TyG-Index were calculated as markers of prevalent hepatic and muscular insulin resistance respectively. Carotid atherosclerosis was assessed by Doppler ultrasonography. The association between cardiovascular risk factors, markers of insulin resistance and carotid atherosclerosis was assessed by multiple logistic regression analyses. In the second cohort, limited to the evaluation of TyG-Index, 1432 subjects were studied. In the first cohort, TyG-Index was significantly associated with carotid atherosclerosis in a model including age, sex, diabetes, cigarette smoking and LDL cholesterol, while HOMA-IR was not. When components of metabolic syndrome were added to the model as dichotomous variables (absent/present), TyG-Index retained its predictive power. The same result was obtained when the metabolic syndrome was added to the model (absence/presence). The association between TyG-Index and carotid atherosclerosis was confirmed in the second cohort. The present findings suggest that TyG-Index is better associated with carotid atherosclerosis than HOMA-IR. © 2013 John Wiley & Sons Ltd.

Activation of liver X receptor decreases atherosclerosis in Ldlr⁻/⁻ mice in the absence of ATP-binding cassette transporters A1 and G1 in myeloid cells.

Science.gov (United States)

Kappus, Mojdeh S; Murphy, Andrew J; Abramowicz, Sandra; Ntonga, Vusisizwe; Welch, Carrie L; Tall, Alan R; Westerterp, Marit

2014-02-01

Liver X receptor (LXR) activators decrease atherosclerosis in mice. LXR activators (1) directly upregulate genes involved in reverse cholesterol transport and (2) exert anti-inflammatory effects mediated by transrepression of nuclear factor-κB target genes. We investigated whether myeloid cell deficiency of ATP-binding cassette transporters A1 and G1 (ABCA1/G1), principal targets of LXR that promote macrophage cholesterol efflux and initiate reverse cholesterol transport, would abolish the beneficial effects of LXR activation on atherosclerosis. LXR activator T0901317 substantially reduced inflammatory gene expression in macrophages lacking ABCA1/G1. Ldlr(-/-) mice were transplanted with Abca1(-/-)Abcg1(-/-) or wild-type bone marrow (BM) and fed a Western-type diet for 6 weeks with or without T0901317 supplementation. Abca1/g1 BM deficiency increased atherosclerotic lesion complexity and inflammatory cell infiltration into the adventitia and myocardium. T0901317 markedly decreased lesion area, complexity, and inflammatory cell infiltration in the Abca1(-/-)Abcg1(-/-) BM-transplanted mice. To investigate whether this was because of macrophage Abca1/g1 deficiency, Ldlr(-/-) mice were transplanted with LysmCreAbca1(fl/fl)Abcg1(fl/fl) or Abca1(fl/fl)Abcg1(fl/fl) BM and fed Western-type diet with or without the more specific LXR agonist GW3965 for 12 weeks. GW3965 decreased lesion size in both groups, and the decrease was more prominent in the LysmCreAbca1(fl/fl)Abcg1(fl/fl) group. The results suggest that anti-inflammatory effects of LXR activators are of key importance to their antiatherosclerotic effects in vivo independent of cholesterol efflux pathways mediated by macrophage ABCA1/G1. This has implications for the development of LXR activators that lack adverse effects on lipogenic genes while maintaining the ability to transrepress inflammatory genes.

Radiofrequency radiation at Stockholm Central Railway Station in Sweden and some medical aspects on public exposure to RF fields

OpenAIRE

Hardell, Lennart; Koppel, Tarmo; Carlberg, Michael; Ahonen, Mikko; Hedendahl, Lena

2016-01-01

The Stockholm Central Railway Station in Sweden was investigated for public radiofrequency (RF) radiation exposure. The exposimeter EME Spy 200 was used to collect the RF exposure data across the railway station. The exposimeter covers 20 different radiofrequency bands from 88 to 5,850 MHz. In total 1,669 data points were recorded. The median value for total exposure was 921 ?W/m2 (or 0.092 ?W/cm2; 1 ?W/m2=0.0001 ?W/cm2) with some outliers over 95,544 ?W/m2 (6 V/m, upper detection limit). The...

Protective role for properdin in progression of experimental murine atherosclerosis.

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Tanja Steiner

Full Text Available Genetic, dietary and immune factors contribute to the pathogenesis of atherosclerosis in humans and mice. Complement activation is an integral part of the innate immune defence but also shapes cellular responses and influences directly triglyceride synthesis. Deficiency of Factor B of the alternative pathway (AP of complement is beneficial in LDLR(-/- mice fed a high fat diet. The serum glycoprotein properdin is a key positive regulator of the AP but has not been studied in experimental atherosclerosis. Atherosclerosis was assessed after feeding low fat (LFD or high fat (HFD Western type diets to newly generated LDLR(-/- Properdin(KO (LDLR(-/-P(KO and LDLR-/-PWT mice. Lipids, lymphocytes and monocytes were similar among genotypes, genders and diets. Complement C3, but not C3adesarg, levels were enhanced in LDLR(-/-P(KO mice regardless of diet type or gender. Non-esterified fatty acids (NEFA were decreased in male LDLR(-/-P(KO fed a HFD compared with controls. All mice showed significant atherosclerotic burden in aortae and at aortic roots but male LDLR(-/- mice fed a LFD were affected to the greatest extent by the absence of properdin. The protective effect of properdin expression was overwhelmed in both genders of LDLR(-/-mice when fed a HFD. We conclude that properdin plays an unexpectedly beneficial role in the development and progression of early atherosclerotic lesions.

Subclinical coronary atherosclerosis and neighbourhood deprivation in an urban region

International Nuclear Information System (INIS)

Dragano, Nico; Hoffmann, Barbara; Stang, Andreas; Moebus, Susanne; Verde, Pablo E.; Weyers, Simone; Moehlenkamp, Stefan; Schmermund, Axel; Mann, Klaus; Joeckel, Karl-Heinz; Erbel, Raimund; Siegrist, Johannes

2009-01-01

Inhabitants of deprived neighbourhoods are at higher risk of coronary heart disease. In this study we investigate the hypothesis that social inequalities at neighbourhood level become already manifest in subclinical coronary atherosclerosis, as defined by electron-beam computed tomography derived measures. Coronary artery calcification was assessed as a marker of atherosclerosis in a population based sample of 4301 men and women (45-75 years) without a history of coronary heart disease. Participants lived in three adjacent cities in Germany and were examined between 2000 and 2003 as part of the Heinz Nixdorf Recall Study. Individual level data was combined with neighbourhood level information about unemployment, welfare and living space per inhabitant. This dataset was analysed with descriptive and multilevel regression methods. An association between neighbourhood deprivation and subclinical coronary calcification was observed. After adjustment for age and individual socioeconomic status male inhabitants of high unemployment neighbourhoods had an odds ratio of 1.45 (1.11, 1.96) of exhibiting a high calcification score (>75th percentile) compared to men living in low unemployment areas. The respective odds for women was 1.29 (0.97, 1.70). Additional explorative analyses suggest that clustering of unhealthy lifestyles in deprived neighbourhoods contributes to the observed association. In conclusion, findings suggest that certain neighbourhood characteristics promote the emergence of coronary atherosclerosis. This might point to a pathway from neighbourhood deprivation to manifest coronary heart disease

Outbreak of enterovirus D68 of the new B3 lineage in Stockholm, Sweden, August to September 2016.

Science.gov (United States)

Dyrdak, Robert; Grabbe, Malin; Hammas, Berit; Ekwall, Jonas; Hansson, Karin E; Luthander, Joachim; Naucler, Pontus; Reinius, Henrik; Rotzén-Östlund, Maria; Albert, Jan

2016-11-17

We report an enterovirus D68 (EV-D68) outbreak in Stockholm Sweden in 2016. Between 22 August and 25 September EV-D68 was detected in 74/495 respiratory samples analysed at the Karolinska University Hospital. During the peak week, 30/91 (33%) samples were EV-D68 positive. Viral protein (VP)P4/VP2 sequencing revealed that cases were caused by B3 lineage strains. Forty-four (59%) EV-D68-positive patients were children aged ≤ 5 years. Ten patients had severe respiratory or neurological symptoms and one died. This article is copyright of The Authors, 2016.

Insulin resistance and atherosclerosis : the role of visceral fat

NARCIS (Netherlands)

Gast, K.B.

2016-01-01

The main objective of this thesis was to unravel relationships between obesity, insulin resistance, hyperglycemia, and atherosclerosis. It is well-established that patients with type 2 diabetes have a 2- to 3-fold increased risk of cardiovascular disease. We investigated whether insulin resistance

Control of Atherosclerosis Regression by PRMT2 in Diabetes

Science.gov (United States)

2017-08-01

Macrophage Dysfunction in Obesity , Diabetes and Atherosclerosis Time Commitment: 3.0 Cal Months Supporting Agency: NHLBI Grants Officer: John Diggs...Project Goals: This sub-project focuses on the kinetics of the macrophage population in atherosclerotic plaques in a mouse model of psychological

Human Low Density Lipoprotein as a Vehicle of Atherosclerosis ...

African Journals Online (AJOL)

Low-density lipoproteins have been sufficiently established as an important precursor of atherosclerosis. The actual mechanism is still unclear, and the current technique of using radioisotopes has clinical limitation. However, the current study techniques or methods excellently elucidate the functional aspects of ...

Changes in expression of proteasome in rats at different stages of atherosclerosis.

Science.gov (United States)

Ismawati; Oenzil, Fadil; Yanwirasti; Yerizel, Eti

2016-06-01

It has been suggested that proteasome system has a role in initiation, progression, and complication stages of atherosclerosis. Although there is still controversy, there has been no research that compares the expression of proteasome in tissue and serum at each of these stages. This study aimed to investigated the expression of proteasome at different stages of atherosclerosis using rat model. We measured the expression of aortic proteasome by immunohistochemical analyses and were then analyzed using ImageJ software for percentage of area and integrated density. We used Photoshop version 3.0 to analyze aortic proteasome expression as a comparison. We measured serum proteasome expression by enzyme linked immunosorbents assays. Kruskal-Wallis test was used to compare mean value of percentage of area and serum proteasome. Analysis of variance test was used to compare mean value of integrated density. Correlation test between vascular proteasome expression and serum proteasome expression was made using Spearman test. A P-value of 0.05 was considered statistically significant. Compared with normal, percentage of area was higher in initiation, progression, and complication. Compared with normal, integrated density was higher in initiation and further higher in progression and complication. Data from Image J is similar with data from Photoshop. Serum proteasome expression was higher in initiation compared with normal, and further higher in progression and complication. It was concluded that there were different vascular proteasome expression and serum proteasome expression at the stages of atherosclerosis. These results may be used in research into new marker and therapeutic target in atherosclerosis.

Citrullus lanatus 'sentinel' (watermelon) extract reduces atherosclerosis in LDL receptor-deficient mice.

Science.gov (United States)

Poduri, Aruna; Rateri, Debra L; Saha, Shubin K; Saha, Sibu; Daugherty, Alan

2013-05-01

Watermelon (Citrullus lanatus or C. lanatus) has many potentially bioactive compounds including citrulline, which may influence atherosclerosis. In this study, we determined the effects of C. lanatus, provided as an extract of the cultivar 'sentinel,' on hypercholesterolemia-induced atherosclerosis in mice. Male low-density lipoprotein receptor-deficient mice at 8 weeks old were given either C. lanatus 'sentinel' extract (2% vol/vol; n=10) or a mixture of matching carbohydrates (2% vol/vol; n=8) as the control in drinking water while being fed a saturated fat-enriched diet for 12 weeks ad libitum. Mice consuming C. lanatus 'sentinel' extract had significantly increased plasma citrulline concentrations. Systolic blood pressure was comparable between the two groups. Consumption of C. lanatus 'sentinel' extract led to lower body weight and fat mass without influencing lean mass. There were no differences in food and water intake and in urine output between the two groups. C. lanatus 'sentinel' extract administration decreased plasma cholesterol concentrations that were attributed to reductions of intermediate-/low-density lipoprotein cholesterol. Plasma concentrations of monocyte chemoattractant protein-1 and interferon-gamma were decreased and those of interleukin-10 were increased in mice consuming C. lanatus 'sentinel' extract. Intake of C. lanatus 'sentinel' extract resulted in reductions of atherosclerosis in both aortic arch and thoracic regions. In conclusion, consumption of C. lanatus 'sentinel' extract led to reduced body weight gain, decreased plasma cholesterol concentrations, improved homeostasis of pro- and anti-inflammatory cytokines, and attenuated development of atherosclerosis without affecting systolic blood pressure in hypercholesterolemic mice. Copyright © 2013 Elsevier Inc. All rights reserved.

Feasibility study on RI biochip Application to detection of risk factors of atherosclerosis

International Nuclear Information System (INIS)

Ko, Kyong Cheol; Choi, Mi Hee; Park, Sang Hyun; Cho, Kyung Hyun; Lee, Ki Teak

2009-01-01

Microarrays can be used to screen thousands of binding events in a parallel and high throughput fashion and are of major importance in discase diagnosis and drug discovery. The use of radioisotope is conventionally regarded as one of the most sensitive detection methods. Atherosclerosis is a common disorder affecting arterial blood vessels. It happens when fat, cholesterol, and other substances made in the arterial blood vessels form a hard substances called plaque. Lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ), a phospholipase A 2 enzyme, is used as a marker for cardiac disease. The detection of Lp-PLA 2 was accomplished by using radioactive [ 3 H-acetyl] PAF as a substrate and a feasibility study on RI biochip application to detection of Lp-PLA 2 , a risk factors of atherosclerosis was performed. Inhibitive activity of a native plant extract was also determined by using the RI biochip. It was found to be applicable to a high-throughput screening of inhibitors for developing atherosclerosis therapeutic agents

Adeno-associated virus LPL(S447X) gene therapy in LDL receptor knockout mice

NARCIS (Netherlands)

Rip, Jaap; Sierts, Jeroen A.; Vaessen, Stefan F. C.; Kastelein, John J. P.; Twisk, Jaap; Kuivenhoven, Jan Albert

2007-01-01

BACKGROUND: Overexpression of lipoprotein lipase (LPL) protects against atherosclerosis in genetically engineered mice. We tested whether a gene therapy vector that delivers human (h) LPL(S447X) cDNA to skeletal muscle could induce similar effects. METHODS: LDL receptor knockout (LDLr-/-) mice were

Reverse association of omega-3/omega-6 polyunsaturated fatty acids ratios with carotid atherosclerosis in patients on hemodialysis.

Science.gov (United States)

Umemoto, Norio; Ishii, Hideki; Kamoi, Daisuke; Aoyama, Toru; Sakakibara, Takashi; Takahashi, Hiroshi; Tanaka, Akihito; Yasuda, Yoshinari; Suzuki, Susumu; Matsubara, Tatsuaki; Murohara, Toyoaki

2016-06-01

Omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are widely recognized to have beneficial effects against cardiovascular disease. We investigated the association of n-3 PUFAs levels with carotid atherosclerosis in patients on hemodialysis (HD), who are at high risk for cardiovascular events. Carotid ultra-sound was performed in a total of 461 patients on HD (male 67%, age 67 ± 12years, diabetes rate 46%). Intima-media thickness (IMT) and the plaque score (PS) in carotid arteries were measured. Carotid atherosclerosis was defined as IMT >1.2 mm and/or PS > 5.0. The levels of n-6 PUFAs [dihomo-gamma-linolenic acid (DHLA) and arachidonic acid (AA)] and n-3 PUFAs [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] were also measured prior to carotid ultra-sound. Carotid atherosclerosis was observed in 94 patients (20.4%). Individual PUFAs levels were comparable between patients with and without carotid atherosclerosis. However, the ratio of EPA/AA and that of n-3/n-6 PUFAs were significantly lower in patients with carotid atherosclerosis compared to those without (median 0.36 vs. 0.41, p = 0.031 and 0.85 vs. 0.93, p = 0.041, respectively]. After adjustment for other confounders, the ratio of EPA/AA (OR 0.30, 95% CI 0.12-0.70, p = 0.0055) and the ratio of n-3/n-6 PUFAs (OR 0.45, 95% CI 0.25-0.80, p = 0.0066) showed an independent reverse association with carotid atherosclerosis. In addition, the area under receiver-operating characteristic curves for carotid atherosclerosis was significantly greater in an established risk model with EPA/AA and n-3/n-6 ratios than in the established risk model alone. These data suggest that low ratios of both EPA/AA ratio and n-3/n-6 PUFAs were closely associated with carotid atherosclerosis in patients on HD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Raman spectroscopy imaging reveals interplay between atherosclerosis and medial calcification in the human aorta

Science.gov (United States)

You, Amanda Y. F.; Bergholt, Mads S.; St-Pierre, Jean-Philippe; Kit-Anan, Worrapong; Pence, Isaac J.; Chester, Adrian H.; Yacoub, Magdi H.; Bertazzo, Sergio; Stevens, Molly M.

2017-01-01

Medial calcification in the human aorta accumulates during aging and is known to be aggravated in several diseases. Atherosclerosis, another major cause of cardiovascular calcification, shares some common aggravators. However, the mechanisms of cardiovascular calcification remain poorly understood. To elucidate the relationship between medial aortic calcification and atherosclerosis, we characterized the cross-sectional distributions of the predominant minerals in aortic tissue, apatite and whitlockite, and the associated extracellular matrix. We also compared the cellular changes between atherosclerotic and nonatherosclerotic human aortic tissues. This was achieved through the development of Raman spectroscopy imaging methods that adapted algorithms to distinguish between the major biomolecules present within these tissues. We present a relationship between apatite, cholesterol, and triglyceride in atherosclerosis, with the relative amount of all molecules concurrently increased in the atherosclerotic plaque. Further, the increase in apatite was disproportionately large in relation to whitlockite in the aortic media directly underlying a plaque, indicating that apatite is more pathologically significant in atherosclerosis-aggravated medial calcification. We also discovered a reduction of β-carotene in the whole aortic intima, including a plaque in atherosclerotic aortic tissues compared to nonatherosclerotic tissues. This unprecedented biomolecular characterization of the aortic tissue furthers our understanding of pathological and physiological cardiovascular calcification events in humans. PMID:29226241

Transendothelial exchange of low-density lipoprotein is unaffected by the presence of severe atherosclerosis

DEFF Research Database (Denmark)

Kornerup, Karen; Nordestgaard, Børge Grønne; Jensen, Trine Krogsgaard

2004-01-01

intravenously (i.v.), and the 1-h fractional escape rates (FER(LDL) and FER(alb)) were taken as indices of transendothelial exchange. RESULTS: Patients with coronary or peripheral atherosclerosis had FER(LDL) similar to that of controls [4.3 (3.5-5.1) and 3.2 (2.3-4.1) versus 4.2 (3.7-4.7)%/h; P>0.05], even...... after adjustment for LDL distribution volume (DV(LDL)). In contrast, diabetes patients had significantly higher FER(LDL) than controls [5.2 (4.6-5.7) versus 4.2 (3.7-4.7)%/h; P..., FER(alb) was not elevated in patients with coronary atherosclerosis, possibly elevated in patients with peripheral atherosclerosis, but was elevated in diabetes patients. There was a tight positive correlation between FER(LDL) and FER(alb) in all groups of patients and controls. CONCLUSION...

IL-25 inhibits atherosclerosis development in apolipoprotein E deficient mice.

Directory of Open Access Journals (Sweden)

Polyxeni T Mantani

Full Text Available IL-25 has been implicated in the initiation of type 2 immunity and in the protection against autoimmune inflammatory diseases. Recent studies have identified the novel innate lymphoid type 2 cells (ILC2s as an IL-25 target cell population. The purpose of this study was to evaluate if IL-25 has any influence on atherosclerosis development in mice.Administration of 1 μg IL-25 per day for one week to atherosclerosis-prone apolipoprotein (apoE deficient mice, had limited effect on the frequency of T cell populations, but resulted in a large expansion of ILC2s in the spleen. The expansion was accompanied by increased levels of anti-phosphorylcholine (PC natural IgM antibodies in plasma and elevated levels of IL-5 in plasma and spleen. Transfer of ILC2s to apoE deficient mice elevated the natural antibody-producing B1a cell population in the spleen. Treatment of apoE/Rag-1 deficient mice with IL-25 was also associated with extensive expansion of splenic ILC2s and increased plasma IL-5, suggesting ILC2s to be the source of IL-5. Administration of IL-25 in IL-5 deficient mice resulted in an expanded ILC2 population, but did not stimulate generation of anti-PC IgM, indicating that IL-5 is not required for ILC2 expansion but for the downstream production of natural antibodies. Additionally, administration of 1 μg IL-25 per day for 4 weeks in apoE deficient mice reduced atherosclerosis in the aorta both during initiation and progression of the disease.The present findings demonstrate that IL-25 has a protective role in atherosclerosis mediated by innate responses, including ILC2 expansion, increased IL-5 secretion, B1a expansion and natural anti-PC IgM generation, rather than adaptive Th2 responses.

Data in support of dyslipidemia-associated alterations in B cell subpopulations frequency and phenotype during experimental atherosclerosis

Directory of Open Access Journals (Sweden)

Héctor Rincón-Arévalo

2016-06-01

Full Text Available Cardiovascular diseases are the most common cause of death in the world, atherosclerosis being its main underlying disease. Information about the role of B cells during atherosclerotic process is scarce, but both proatherogenic and atheroprotective properties have been described in the immunopathology of this disease. Frequency and phenotype of B cell subpopulations were studied in wild type and apolipoprotein-E-deficient (apoE−/− mice fed or not with high-fat diet (HFD, by flow cytometry. Here, we provide the information about the materials, methods, analysis and additional information related to our study published in Atherosclerosis (DOI: 10.1016/j.atherosclerosis.2015.12.022, article reference: ATH14410 [1]. The data contained in this article shows and supports that mice with advanced atherosclerosis have a variety of alterations in frequency and phenotype of B cell subsets, most of which associated with dyslipidemia.

Data in support of dyslipidemia-associated alterations in B cell subpopulations frequency and phenotype during experimental atherosclerosis

Science.gov (United States)

Rincón-Arévalo, Héctor; Castaño, Diana; Villa-Pulgarín, Janny; Rojas, Mauricio; Vásquez, Gloria; Correa, Luis A.; Ramírez-Pineda, José R.; Yassin, Lina M.

2016-01-01

Cardiovascular diseases are the most common cause of death in the world, atherosclerosis being its main underlying disease. Information about the role of B cells during atherosclerotic process is scarce, but both proatherogenic and atheroprotective properties have been described in the immunopathology of this disease. Frequency and phenotype of B cell subpopulations were studied in wild type and apolipoprotein-E-deficient (apoE−/−) mice fed or not with high-fat diet (HFD), by flow cytometry. Here, we provide the information about the materials, methods, analysis and additional information related to our study published in Atherosclerosis (DOI: 10.1016/j.atherosclerosis.2015.12.022, article reference: ATH14410) [1]. The data contained in this article shows and supports that mice with advanced atherosclerosis have a variety of alterations in frequency and phenotype of B cell subsets, most of which associated with dyslipidemia. PMID:27081674

Pleiotropic role of growth arrest-specific gene 6 in atherosclerosis

NARCIS (Netherlands)

Tjwa, Marc; Moons, Lieve; Lutgens, Esther

2009-01-01

Growth arrest-specific gene 6 (Gas6) belongs to the family of vitamin K-dependent coagulation proteins, but in contrast to its other members, has only a limited role in hemostasis. Instead, Gas6 plays a prominent role in conditions of injury, inflammation and repair. Gas6 amplifies the activation of

Effect of tocotrienol on aortic atherosclerosis in diabetic mice

International Nuclear Information System (INIS)

Kiani, M.R.B.; Butt, S.A.; Ahmed, T.

2015-01-01

Effect of tocotrienol on aortic atherosclerosis in diabetic mice To study the histomorphological effect of tocotrienol on aortic atherosclerosis in diabetic mice having high fat diet. Study Design: Lab based randomized controlled trial. Place and Duration of Study: Army Medical College, Rawalpindi and National Institute of Health, Islamabad from November 2009 to June 2010. Material and Methods: Forty five female BALB/c mice were randomly divided into three groups. The diabetic mice model was established by intraperitoneal injection of streptozotocin (STZ) 40 mg/kg body weight. Group A was given normal laboratory diet, group B high fat diet and group C was given tocotrienol along with high fat diet for 32 weeks. At the end of experiment the mice were sacrificed. The hearts of animals were dissected out and ascending aortae were taken out. The specimen was fixed in 10% formol calcium and processed for paraffin embedding. Five micrometer thick sections were made for haematoxylin and eosin, and Verhoeff's staining. After staining, histomorphologic changes in slides were noted. Results: In contrast to group A, atheroscelrosis developed in groups B and C. Statistically significant atherosclerotic changes were found in the aortae of diabetic mice in group B when compared to group A. On comparison of group A to C, atherosclerotic changes were statistically insignificant. However when group B was compared with group C, the aortic atherosclerotic changes decreased significantly in group C. Conclusion: In diabetics with high fat diet intake, there is an increase in development of atherosclerosis in aorta which can be reduced by tocotrienol. (author)

A CD1d-dependent lipid antagonist to NKT cells ameliorates atherosclerosis in ApoE-/- mice by reducing lesion necrosis and inflammation.

Science.gov (United States)

Li, Yi; Kanellakis, Peter; Hosseini, Hamid; Cao, Anh; Deswaerte, Virginie; Tipping, Peter; Toh, Ban-Hock; Bobik, Alex; Kyaw, Tin

2016-02-01

Atherosclerosis-related deaths from heart attacks and strokes remain leading causes of global mortality, despite the use of lipid-lowering statins. Thus, there is an urgent need to develop additional therapies. Reports that NKT cells promote atherosclerosis and an NKT cell CD1d-dependent lipid antagonist (DPPE-PEG350, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N[methoxy(polyethyleneglycol)-350]) reduces allergen-induced inflammation led us to investigate its therapeutic potential in preventing the development and progression of experimental atherosclerosis. DPPE-PEG350 was administered to hyperlipidaemic ApoE(-/-) mice with/without established atherosclerosis. Atherosclerosis and immune cells were assessed in the aortic sinus lesions. Lesion expression of monocyte chemoattractant protein-1 (MCP-1) and vascular cell adhesion protein-1 (VCAM-1) responsible for inflammatory immune cell recruitment as well as mRNA expression of IFNγ and its plasma levels were investigated. Necrotic cores and lesion smooth muscle and collagen contents important in plaque stability were determined as were plasma lipid levels. DPPE-PEG350 reduced atherosclerosis development and delayed progression of established atherosclerosis without affecting plasma lipids. CD4 and CD8 T cells and B cells in atherosclerotic lesions were decreased in DPPE-PEG350-treated mice. Lesion MCP-1 and VCAM-1 protein expression and necrotic core size were reduced without affecting lesion smooth muscle and collagen content. IFNγ and lymphocytes were unaffected by the treatment. The attenuation of progression of established atherosclerosis together with reduced development of atherosclerosis in hyperlipidaemic mice by the NKT antagonist, without affecting NKT cell or other lymphocyte numbers, suggests that targeting lesion inflammation via CD1d-dependent activation of NKT cells using DPPE-PEG350 has a therapeutic potential in treating atherosclerosis. Published on behalf of the European Society of

Cholesteryl ester transfer protein decreases high-density lipoprotein and severely aggravates atherosclerosis in APOE*3-Leiden mice

NARCIS (Netherlands)

Westerterp, M.; Hoogt, C.C. van der; Haan, W. de; Offerman, E.H.; Dallinga-Thie, G.M.; Jukema, J.W.; Havekes, L.M.; Rensen, P.C.N.

2006-01-01

OBJECTIVE - The role of cholesteryl ester transfer protein (CETP) in the development of atherosclerosis is still undergoing debate. Therefore, we evaluated the effect of human CETP expression on atherosclerosis in APOE*3-Leiden (E3L) mice with a humanized lipoprotein profile. METHODS AND RESULTS -

Phytosterols and atherosclerosis

DEFF Research Database (Denmark)

Schrøder, Malene

for decades for their natural ability to reduce cholesterol levels in the blood. In the last decade numerous food products added phytosterol esters have been placed on the market, e.g. yellow fat spread, yoghurt, dressing. The products are being marketed as a natural means for people who want to lower...... or advanced lesion) and quantitatively by stereological methods applied to evaluate the area of the intima and the ratio of intima:media on cross sections from three defined places on the aorta. The biochemical endpoint was the cholesterol content in the inner layer of the entire aorta, which is considered...... than 3% brassicasterol are not accepted on the European market. The aim of the study was to investigate the effect of dietary supplementation of RSO derived sterol, with high content of brassicasterols, and stanol esters on the development of atherosclerosis in cholesterol-fed heterozygous WHHL rabbits...

Potential Biomarkers of Insulin Resistance and Atherosclerosis in Type 2 Diabetes Mellitus Patients with Coronary Artery Disease

Directory of Open Access Journals (Sweden)

Sharifah Intan Qhadijah Syed Ikmal

2013-01-01

Full Text Available Type 2 diabetes mellitus patients with coronary artery disease have become a major public health concern. The occurrence of insulin resistance accompanied with endothelial dysfunction worsens the state of atherosclerosis in type 2 diabetes mellitus patients. The combination of insulin resistance and endothelial dysfunction leads to coronary artery disease and ischemic heart disease complications. A recognized biological marker, high-sensitivity C-reactive protein, has been used widely to assess the progression of atherosclerosis and inflammation. Along with coronary arterial damage and inflammatory processes, high-sensitivity C-reactive protein is considered as an essential atherosclerosis marker in patients with cardiovascular disease, but not as an insulin resistance marker in type 2 diabetes mellitus patients. A new biological marker that can act as a reliable indicator of both the exact state of insulin resistance and atherosclerosis is required to facilitate optimal health management of diabetic patients. Malfunctioning of insulin mechanism and endothelial dysfunction leads to innate immune activation and released several biological markers into circulation. This review examines potential biological markers, YKL-40, alpha-hydroxybutyrate, soluble CD36, leptin, resistin, interleukin-18, retinol binding protein-4, and chemerin, as they may play significant roles in insulin resistance and atherosclerosis in type 2 diabetes mellitus patients with coronary artery disease.

Relationship of Hypertension to Coronary Atherosclerosis and Cardiac Events in Patients With Coronary Computed Tomographic Angiography.

Science.gov (United States)

Nakanishi, Rine; Baskaran, Lohendran; Gransar, Heidi; Budoff, Matthew J; Achenbach, Stephan; Al-Mallah, Mouaz; Cademartiri, Filippo; Callister, Tracy Q; Chang, Hyuk-Jae; Chinnaiyan, Kavitha; Chow, Benjamin J W; DeLago, Augustin; Hadamitzky, Martin; Hausleiter, Joerg; Cury, Ricardo; Feuchtner, Gudrun; Kim, Yong-Jin; Leipsic, Jonathon; Kaufmann, Philipp A; Maffei, Erica; Raff, Gilbert; Shaw, Leslee J; Villines, Todd C; Dunning, Allison; Marques, Hugo; Pontone, Gianluca; Andreini, Daniele; Rubinshtein, Ronen; Bax, Jeroen; Jones, Erica; Hindoyan, Niree; Gomez, Millie; Lin, Fay Y; Min, James K; Berman, Daniel S

2017-08-01

Hypertension is an atherosclerosis factor and is associated with cardiovascular risk. We investigated the relationship between hypertension and the presence, extent, and severity of coronary atherosclerosis in coronary computed tomographic angiography and cardiac events risk. Of 17 181 patients enrolled in the CONFIRM registry (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry) who underwent ≥64-detector row coronary computed tomographic angiography, we identified 14 803 patients without known coronary artery disease. Of these, 1434 hypertensive patients were matched to 1434 patients without hypertension. Major adverse cardiac events risk of hypertension and non-hypertensive patients was evaluated with Cox proportional hazards models. The prognostic associations between hypertension and no-hypertension with increasing degree of coronary stenosis severity (nonobstructive or obstructive ≥50%) and extent of coronary artery disease (segment involvement score of 1-5, >5) was also assessed. Hypertension patients less commonly had no coronary atherosclerosis and more commonly had nonobstructive and 1-, 2-, and 3-vessel disease than the no-hypertension group. During a mean follow-up of 5.2±1.2 years, 180 patients experienced cardiac events, with 104 (2.0%) occurring in the hypertension group and 76 (1.5%) occurring in the no-hypertension group (hazard ratios, 1.4; 95% confidence intervals, 1.0-1.9). Compared with no-hypertension patients without coronary atherosclerosis, hypertension patients with no coronary atherosclerosis and obstructive coronary disease tended to have higher risk of cardiac events. Similar trends were observed with respect to extent of coronary artery disease. Compared with no-hypertension patients, hypertensive patients have increased presence, extent, and severity of coronary atherosclerosis and tend to have an increase in major adverse cardiac events. © 2017 American Heart Association, Inc.

Identification of the human ApoAV gene as a novel RORα target gene

International Nuclear Information System (INIS)

Lind, Ulrika; Nilsson, Tina; McPheat, Jane; Stroemstedt, Per-Erik; Bamberg, Krister; Balendran, Clare; Kang, Daiwu

2005-01-01

Retinoic acid receptor-related orphan receptor-α (RORα) (NR1F1) is an orphan nuclear receptor with a potential role in metabolism. Previous studies have shown that RORα regulates transcription of the murine Apolipoprotein AI gene and human Apolipoprotein CIII genes. In the present study, we present evidence that RORα also induces transcription of the human Apolipoprotein AV gene, a recently identified apolipoprotein associated with triglyceride levels. Adenovirus-mediated overexpression of RORα increased the endogenous expression of ApoAV in HepG2 cells and RORα also enhanced the activity of an ApoAV promoter construct in transiently transfected HepG2 cells. Deletion and mutation studies identified three AGGTCA motifs in the ApoAV promoter that mediate RORα transactivation, one of which overlaps with a previously identified binding site for PPARα. Together, these results suggest a novel mechanism whereby RORα modulates lipid metabolism and implies RORα as a potential target for the treatment of dyslipidemia and atherosclerosis

Molecular imaging of inflammation in the ApoE -/- mouse model of atherosclerosis with IodoDPA

Energy Technology Data Exchange (ETDEWEB)

Foss, Catherine A., E-mail: cfoss1@jhmi.edu [Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287 (United States); Bedja, Djahida [Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287 (United States); Faculty of Medicine and Health Sciences, Macquarie University, Sydney (Australia); Mease, Ronnie C.; Wang, Haofan [Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287 (United States); Kass, David A. [Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287 (United States); Chatterjee, Subroto [Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287 (United States); Pomper, Martin G. [Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287 (United States)

2015-05-22

Background: Atherosclerosis is a common and serious vascular disease predisposing individuals to myocardial infarction and stroke. Intravascular plaques, the pathologic lesions of atherosclerosis, are largely composed of cholesterol-laden luminal macrophage-rich infiltrates within a fibrous cap. The ability to detect those macrophages non-invasively within the aorta, carotid artery and other vessels would allow physicians to determine plaque burden, aiding management of patients with atherosclerosis. Methods and results: We previously developed a low-molecular-weight imaging agent, [{sup 125}I]iodo-DPA-713 (iodoDPA), which selectively targets macrophages. Here we use it to detect both intravascular macrophages and macrophage infiltrates within the myocardium in the ApoE -/- mouse model of atherosclerosis using single photon emission computed tomography (SPECT). SPECT data were confirmed by echocardiography, near-infrared fluorescence imaging and histology. SPECT images showed focal uptake of radiotracer at the aortic root in all ApoE -/- mice, while the age-matched controls were nearly devoid of radiotracer uptake. Focal radiotracer uptake along the descending aorta and within the myocardium was also observed in affected animals. Conclusions: IodoDPA is a promising new imaging agent for atherosclerosis, with specificity for the macrophage component of the lesions involved. - Highlights: • [{sup 125}I]iodoDPA SPECT detects atherosclerotic plaques in ApoE -/- mice with high contrast. • Plaques are detected in ApoE -/- mice regardless of diet with iodoDPA. • iodoDPA has very low uptake in healthy tissue including healthy TSPO + tissues at 24 h.

Relation of ABO blood groups to the severity of coronary atherosclerosis: an Gensini score assessment.

Science.gov (United States)

Gong, Ping; Luo, Song-Hui; Li, Xiao-Lin; Guo, Yuan-Lin; Zhu, Cheng-Gang; Xu, Rui-Xia; Li, Sha; Dong, Qian; Liu, Geng; Chen, Juan; Zeng, Rui-Xiang; Li, Jian-Jun

2014-12-01

Although the study on the relationship between ABO blood groups and coronary atherosclerosis has a long history, few data is available regarding ABO to severity of coronary atherosclerosis in a large cohort study. Therefore, the present study aimed to investigate the relation of the ABO blood groups to the severity of coronary atherosclerosis assessed by Gensini score (GS) in a large Chinese cohort undergoing coronary angiography. A total of 2919 consecutive patients undergoing coronary angiography were enrolled, and their baseline characteristics and ABO blood groups were collected. The GS was calculated as 1st tertile (0-10), 2nd tertile (11-36), 3rd tertile (>36) according to angiographic results. The relation of the ABO blood groups to GS was investigated. The frequency of blood group A was significantly higher in the upper GS tertiles (24.4% vs. 28.2% vs. 29.5%, p = 0.032). Multivariable linear regression analysis revealed that blood group A was independently associated with GS (β = 0.043, p = 0.017). Likewise, multivariable logistic regression analysis showed that group A remained significantly associated with mid-high GS (OR = 1.44, 95% CI 1.16-1.80, p = 0.001), and the group O was showed as a protective factor (OR = 0.77, 95% CI = 0.65-0.92, p = 0.004). In this large Chinese cohort study, the data indicated that there was an association between ABO blood groups and the severity of coronary atherosclerosis. Moreover, the blood group A was an independent risk factor for serious coronary atherosclerosis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Bone Morphogenetic Protein-Induced Msx1 and Msx2 Inhibit Myocardin-Dependent Smooth Muscle Gene Transcription▿

OpenAIRE

Hayashi, Ken'ichiro; Nakamura, Seiji; Nishida, Wataru; Sobue, Kenji

2006-01-01

During the onset and progression of atherosclerosis, the vascular smooth muscle cell (VSMC) phenotype changes from differentiated to dedifferentiated, and in some cases, this change is accompanied by osteogenic transition, resulting in vascular calcification. One characteristic of dedifferentiated VSMCs is the down-regulation of smooth muscle cell (SMC) marker gene expression. Bone morphogenetic proteins (BMPs), which are involved in the induction of osteogenic gene ex...

Increased activity of vascular adenosine deaminase in atherosclerosis and therapeutic potential of its inhibition.

Science.gov (United States)

Kutryb-Zajac, Barbara; Mateuszuk, Lukasz; Zukowska, Paulina; Jasztal, Agnieszka; Zabielska, Magdalena A; Toczek, Marta; Jablonska, Patrycja; Zakrzewska, Agnieszka; Sitek, Barbara; Rogowski, Jan; Lango, Romuald; Slominska, Ewa M; Chlopicki, Stefan; Smolenski, Ryszard T

2016-11-01

Extracellular nucleotides and adenosine that are formed or degraded by membrane-bound ecto-enzymes could affect atherosclerosis by regulating the inflammation and thrombosis. This study aimed to evaluate a relation between ecto-enzymes that convert extracellular adenosine triphosphate to adenine dinucleotide phosphate, adenosine monophosphate, adenosine, and inosine on the surface of the vessel wall with the severity or progression of experimental and clinical atherosclerosis. Furthermore, we tested whether the inhibition of adenosine deaminase will block the development of experimental atherosclerosis. Vascular activities of ecto-nucleoside triphosphate diphosphohydrolase 1, ecto-5'-nucleotidase, and ecto-adenosine deaminase (eADA) were measured in aortas of apolipoprotein E-/- low density lipoprotein receptor (ApoE-/-LDLR-/-) and wild-type mice as well as in human aortas. Plaques were analysed in the entire aorta, aortic root, and brachiocephalic artery by Oil-Red O and Orcein Martius Scarlet Blue staining and vascular accumulation of macrophages. The cellular location of ecto-enzymes was analysed by immunofluorescence. The effect of eADA inhibition on atherosclerosis progression was studied by a 2-month deoxycoformycin treatment of ApoE-/-LDLR-/- mice. The vascular eADA activity prominently increased in ApoE-/-LDLR-/- mice when compared with wild type already at the age of 1 month and progressed along atherosclerosis development, reaching a 10-fold difference at 10 months. The activity of eADA correlated with atherosclerotic changes in human aortas. High abundance of eADA in atherosclerotic vessels originated from activated endothelial cells and macrophages. There were no changes in ecto-nucleoside triphosphate diphosphohydrolase 1 activity, whereas ecto-5'-nucleotidase was moderately decreased in ApoE-/-LDLR-/- mice. Deoxycoformycin treatment attenuated plaque development in aortic root and brachiocephalic artery of ApoE-/-LDLR-/- mice, suppressed vascular

Endometriosis and atherosclerosis: what we already know and what we have yet to discover.

Science.gov (United States)

Santoro, Luca; D'Onofrio, Ferruccio; Flore, Roberto; Gasbarrini, Antonio; Santoliquido, Angelo

2015-09-01

The possible association between endometriosis and atherosclerosis represents an emerging topic in the field of women's health. In this Clinical Opinion paper, we analyze this theme focusing on the pathogenetic mechanisms of both diseases, deeply discussing about what is already known about this association and producing starting points about what we consider suitable to research in the near future with regard to cardiovascular involvement in women affected by endometriosis. We have identified 5 reports specifically carried out to investigate the relationship between atherosclerosis and endometriosis; these studies show the presence of subclinical atherosclerosis in women affected by endometriosis, susceptible of regression after surgical removal of endometriosis, with a possible prognostic relevance for variations of cardiovascular risk in these women. However, to date, no studies in literature have been carried out to investigate the real incidence of cardiovascular events in women with endometriosis. Copyright © 2015 Elsevier Inc. All rights reserved.

Relationship between inter-arm blood pressure difference and severity of coronary atherosclerosis.

Science.gov (United States)

Park, Se-Jun; Son, Jung-Woo; Park, Sang-Min; Choi, Hyun-Hee; Hong, Kyung-Soon

2017-08-01

A greater inter-arm blood pressure difference (IABPD) is associated with atherosclerosis, but its association with coronary artery disease is unknown. We investigated the relationship between IABPD and coronary atherosclerosis. We retrospectively reviewed blood pressure (BP) data that was measured simultaneously in both arms of patients who underwent initial coronary angiography. Coronary atherosclerosis was assessed using the Gensini score, based on quantitative coronary angiography findings. To adjust for the effect of baseline BP, the percentages of systolic IABPD to higher mean BP (cIABPD sys ), diastolic IABPD to higher mean BP (cIABPD dia ), and mean IABPD to higher mean BP (cIABPD mean ) were calculated as BP-adjusted IABPDs. We examined the records of 816 patients (516 males, mean age: 65.5 ± 11.8 years). The mean Gensini score was 33.4 ± 30.4, and the median was 25. All cIAPBDs had positive correlations with the Gensini score (cIABPD sys : r = 0.208, p < 0.001; cIABPD dia : r = 0.123, p < 0.001; cIABPD mean : r = 0.120, p = 0.001). Multiple regression analysis indicated that cIABPD sys was associated with the Gensini score, independently of age, gender, smoking, diabetes, hypertension and dyslipidemia (B = 0.031, p < 0.001). The BP-adjusted IABPD parameters are related to the severity of coronary artery disease. Further studies should investigate the use of the IABPD to improve management of coronary atherosclerosis. Copyright © 2017. Published by Elsevier B.V.

Role of parnaparin in atherosclerosis.

Science.gov (United States)

Bonomini, Francesca; Taurone, Samanta; Parnigotto, Pierpaolo; Zamai, Loris; Rodella, Luigi F; Artico, Marco; Rezzani, Rita

2016-12-01

Atherosclerosis is characterized by a proliferation of vascular smooth muscle cells (VSMCs) and their migration to the intima, which induces thickening of the intima itself, but the mechanism remains poorly understood. Low molecular weight heparin (LMWH) inhibits the proliferation of VSMCs. Previous studies have shown that a LMWH, parnaparin (PNP), acts on the processes of atherogenesis and atheroprogression in experimental animal models. The aim of this study was to investigate the involvement of oxidative stress, inflammation and VSMCs in the regulation of vascular wall homeostasis. We also considered the possibility of restoring vascular pathological changes using PNP treatment. In order to evaluate vascular remodelling in this study we have analysed the morphological changes in aortas of an animal model of atherosclerosis, apolipoprotein E-deficient mice (ApoE-/-) fed with a normal or a western diet without treatment or treated with PNP. We also analysed, by immunohistochemistry, the expression of proteins linked to atherogenesis and atheroprogression - an enzyme involved in oxidative stress, iNOS, examples of inflammatory mediators, such as tumour necrosis factor alpha (TNF-α), interleukins 1 and 6 (IL-1 and IL-6), and markers of VSMC changes, in particular plasminogen activator inhibitor-1 and thrombospondin-1 (PAI-1 and TSP-1). Our results could suggest that PNP downregulates VSMC proliferation and migration, mediated by PAI-1 and TSP-1, and reduces inflammation and oxidative stress in vessels. These data suggested that LMWH, in particular PNP, could be a theoretically practical tool in the prevention of atherosclerotic vascular modification. © 2017 The Authors. International Journal of Experimental Pathology © 2017 International Journal of Experimental Pathology.

Sphingosine 1-Phosphate and Atherosclerosis

Science.gov (United States)

Yatomi, Yutaka

2018-01-01

Sphingosine 1-phosphate (S1P) is a potent lipid mediator that works on five kinds of S1P receptors located on the cell membrane. In the circulation, S1P is distributed to HDL, followed by albumin. Since S1P and HDL share several bioactivities, S1P is believed to be responsible for the pleiotropic effects of HDL. Plasma S1P levels are reportedly lower in subjects with coronary artery disease, suggesting that S1P might be deeply involved in the pathogenesis of atherosclerosis. In basic experiments, however, S1P appears to possess both pro-atherosclerotic and anti-atherosclerotic properties; for example, S1P possesses anti-apoptosis, anti-inflammation, and vaso-relaxation properties and maintains the barrier function of endothelial cells, while S1P also promotes the egress and activation of lymphocytes and exhibits pro-thrombotic properties. Recently, the mechanism for the biased distribution of S1P on HDL has been elucidated; apolipoprotein M (apoM) carries S1P on HDL. ApoM is also a modulator of S1P, and the metabolism of apoM-containing lipoproteins largely affects the plasma S1P level. Moreover, apoM modulates the biological properties of S1P. S1P bound to albumin exerts both beneficial and harmful effects in the pathogenesis of atherosclerosis, while S1P bound to apoM strengthens anti-atherosclerotic properties and might weaken the pro-atherosclerotic properties of S1P. Although the detailed mechanisms remain to be elucidated, apoM and S1P might be novel targets for the alleviation of atherosclerotic diseases in the future. PMID:28724841

C242T Polymorphism in CYBA Gene (p22phox and Risk of Coronary Artery Disease in a Population of Caucasian Italians

Directory of Open Access Journals (Sweden)

Sabina Nasti

2006-01-01

Full Text Available Background: specific polymorphisms of genes regulating intracellular redox balance and oxidative stress are related to atherogenesis. Some studies have identified a relationship between progression of atherosclerosis and C242T mutation in CYBA gene coding for p22phox, a subunit of the NADH/NADPH oxidase system.

Sudden death related to advanced coronary atherosclerosis in mini-pigs

International Nuclear Information System (INIS)

Jacobsson, L.; Lundholm, L.; Wingren, G.

1984-01-01

Advanced coronary atherosclerosis was produced in 30 mini-pigs by a combination of a hypercholesterolaemic diet and X-irradiation to the precordial region. Within 11-25 weeks after the irradiation, 13 of the 30 animals died a sudden death probably caused by coronary atherosclerosis. The contents of free and ester-bound cholesterol in the right coronary artery were significantly higher in the animals which died spontaneously than in surviving animals. In an untreated group of 12 animals 7 died whereas in a group treated with β-pyridylcarbinol only 1 out of 5 died. In the coronary arteries, the contents of both free and ester-bound cholesterol were significantly lower in the β-pyridylcarbinol-treated animals. In a sulfinpyrazontreated group 3 out of 8, and in a metoprolol-treated group 2 out of 5 animals died. None of these drugs reduced the accumulation of cholesterol in the coronary arteries. The rate of sudden death was 26 +- 6% (P<0.05) lower in the combined group of treated animals than in the untreated ones. By regular ECG recordings, signs which could predict the fatal outcome of the experiment were looked for. Although depressed ST segments were present before death in a few animals, this was not a regular phenomenon. It is concluded that advanced coronary atherosclerosis in mini-pigs often leads to sudden death and that this animal model seems suitable for testing the potential therapeutic effects of drugs. (author)

Immunoproteasome subunit ß5i/LMP7-deficiency in atherosclerosis.

Science.gov (United States)

Hewing, Bernd; Ludwig, Antje; Dan, Cristian; Pötzsch, Max; Hannemann, Carmen; Petry, Andreas; Lauer, Dilyara; Görlach, Agnes; Kaschina, Elena; Müller, Dominik N; Baumann, Gert; Stangl, Verena; Stangl, Karl; Wilck, Nicola

2017-10-17

Management of protein homeostasis by the ubiquitin-proteasome system is critical for atherosclerosis development. Recent studies showed controversial results on the role of immunoproteasome (IP) subunit β5i/LMP7 in maintenance of protein homeostasis under cytokine induced oxidative stress. The present study aimed to investigate the effect of β5i/LMP7-deficiency on the initiation and progression of atherosclerosis as a chronic inflammatory, immune cell driven disease. LDLR -/- LMP7 -/- and LDLR -/- mice were fed a Western-type diet for either 6 or 24 weeks to induce early and advanced stage atherosclerosis, respectively. Lesion burden was similar between genotypes in both stages. Macrophage content and abundance of polyubiquitin conjugates in aortic root plaques were unaltered by β5i/LMP7-deficiency. In vitro experiments using bone marrow-derived macrophages (BMDM) showed that β5i/LMP7-deficiency did not influence macrophage polarization or accumulation of polyubiquitinated proteins and cell survival upon hydrogen peroxide and interferon-γ treatment. Analyses of proteasome core particle composition by Western blot revealed incorporation of standard proteasome subunits in β5i/LMP7-deficient BMDM and spleen. Chymotrypsin-, trypsin- and caspase-like activities assessed by using short fluorogenic peptides in BMDM whole cell lysates were similar in both genotypes. Taken together, deficiency of IP subunit β5i/LMP7 does not disturb protein homeostasis and does not aggravate atherogenesis in LDLR -/- mice.

[Association between IGF system and PAPP-A in coronary atherosclerosis].

Science.gov (United States)

Fierro-Macías, Alfonso Eduardo; Floriano-Sánchez, Esaú; Mena-Burciaga, Victoria Michelle; Gutiérrez-Leonard, Hugo; Lara-Padilla, Eleazar; Abarca-Rojano, Edgar; Fierro-Almanzán, Alfonso Edmundo

2016-01-01

Atherosclerosis is a condition that involves multiple pathophysiological mechanisms and whose knowledge has not been fully elucidated. Often, scientific advances on the atherogenic pathophysiology generate that molecules not previously considered in the scene of this disease, were attributed actions on the onset or progression of it. A representative example is the study of a new mechanism involved in the atherogenic process, consisting of the association between the insulin-like growth factor (IGF) system and pregnancy-associated plasma protein-A (PAPP-A). Insulin-like growth factor system is a family of peptides that include 3 peptide hormones, 4 transmembrane receptors and 6 binding proteins. Insulin-like growth factor-1 (IGF-1) is the main ligand of the IGF system involved in coronary atherosclerosis. IGF-1 exerts its effects via activation of the IGF-1R receptor on vascular smooth muscle cells or macrophages. In vascular smooth muscle cells promotes migration and prevents apoptosis which increases plaque stability while in macrophages reduces reverse cholesterol transport leading to the formation of foam cells. Regulation of IGF-1 endothelial bioavailability is carried out by IGFBP proteases, mainly by PAPP-A. In this review, we address the mechanisms between IGF system and PAPP-A in atherosclerosis with emphasis on molecular effects on vascular smooth muscle cells and macrophages. Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

Do tax incentives affect households' adoption of ‘green’ cars? A panel study of the Stockholm congestion tax

International Nuclear Information System (INIS)

Mannberg, Andrea; Jansson, Johan; Pettersson, Thomas; Brännlund, Runar; Lindgren, Urban

2014-01-01

Policymakers have made several attempts to introduce local and national policies to reduce CO 2 emissions and stimulate the consumer adoption of alternative fuel vehicles (ethanol/E85 cars). The purpose of this paper is to analyze how a local policy measure impacts the composition of the car fleet over time. More specifically, we take advantage of the natural experiment setting caused by the introduction of the Stockholm congestion tax (2006) to analyze how the tax affected purchases of ethanol cars that were exempted from the tax. To estimate effects, we employ a Difference-in-differences methodology. By using a comprehensive database of the car fleet and car owners, sociodemographic and geographic factors are analyzed, which is unique in the existing literature. Our results suggest that the congestion tax had a significant impact on ethanol car purchases although the effect fades away over time. Furthermore, there is a positive relationship between the level of education and ethanol car purchases. Previous adoption of an ethanol car is found to be the strongest predictor of ethanol car purchases. Finally, data indicate that Stockholmers substantially increased purchases of ethanol cars half a year before the introduction of the congestion tax, which we refer to as an anticipation effect. - Highlights: • Uses a database of car owners to analyze impacts of a congestion tax on car fleet. • Results show that the tax had a significant effect on ethanol car purchases. • Prior ownership of ethanol car and education correlates with ethanol car purchases

Joint physical custody, turning to parents for emotional support, and subjective health: A study of adolescents in Stockholm, Sweden.

Science.gov (United States)

Låftman, Sara Brolin; Bergström, Malin; Modin, Bitte; Östberg, Viveca

2014-07-01

Among children with separated parents, the arrangement of joint physical custody, i.e. children living equally much in both parents' homes, has increased substantially during the last decades in Sweden. To date, empirical research on the living conditions of this group is limited. This study analyses family type differences in turning to parents for emotional support and in subjective health among adolescents. The focus of the study is adolescents in joint physical custody, who are compared with those living with two original parents in the same household; those living (only) in a single-parent household; and those living (only) in a reconstituted family. The data come from the Stockholm School Survey of 2004, a total population survey of students in grade 9 (15-16 years) in Stockholm (n=8,840). Ordinary least squares (OLS) regressions were conducted. Turning to both parents about problems is most commonly reported by adolescents in intact families, followed by those in joint physical custody. Adolescents in non-traditional family types report worse subjective health than adolescents in intact families, but the difference is smaller for those in joint physical custody than for those living with a single parent. The slightly poorer health of adolescents in joint physical custody than those in intact families is not explained by their lower use of parents as a source of emotional support. The study suggests that joint physical custody is associated with a higher inclination to use parents as a source of emotional support and better subjective health than other post-divorce family types. © 2014 the Nordic Societies of Public Health.

Time trends in 20 years of medication use in older adults: Findings from three elderly cohorts in Stockholm, Sweden.

Science.gov (United States)

Craftman, Åsa Gransjön; Johnell, Kristina; Fastbom, Johan; Westerbotn, Margareta; von Strauss, Eva

2016-01-01

New drugs and expanded drug indications are constantly being introduced. Welfare states strive to provide equity in drug treatment for all of its citizens and todaýs healthcare systems spend financial resources on drugs for the elderly in a higher rate than for any other age group. Drug utilization in elderly persons has an impact in health and wellbeing in older people. It was to describe the changes in medication use including people aged 78 years and over regardless of residence and other characteristics over 20 years. The study population consisted of 4304 participants in three population-based cross-sectional surveys conducted in the Kungsholmen area of central Stockholm, Sweden. The participant's current drug utilization was reviewed by physicians following standardized protocols. Data were statistical analyzed. Logistic regression models was used to estimate odds ratios and 95% confidence intervals for use of analgesics and psychotropic drugs in the cohorts of 2001 and 2007, controlling for age, gender, education and cognition. Results shows that the prevalence of medication use and polypharmacy in older adults has increased dramatically the late 1980s to the 2000s in central Stockholm, Sweden. In particular, the use of analgesics increased significantly, while some drug groups decreased, i.e., antipsychotics. Women used more medication than men in all three cohorts. Older adults living in service buildings used the largest amount of drugs in 1987, whereas those living in institutions were the most frequent users in 2001 and 2007. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Migraine and subclinical atherosclerosis in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

Science.gov (United States)

Goulart, Alessandra C; Santos, Itamar S; Bittencourt, Márcio S; Lotufo, Paulo A; Benseñor, Isabela M

2016-08-01

The relationship between migraine and coronary heart disease (CHD) remains controversial. We aimed to investigate the association of subclinical atherosclerosis and migraine with or without aura compared to a non-migraine subgroup (reference) in a large Brazilian multicentric cohort study, the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Migraine diagnostic was based on International Headache Society criteria, and aura symptoms were validated by a medical doctor in a sub-sample of the ELSA-Brasil, who also underwent coronary artery calcium score (CAC) and carotid intima-media thickness (C-IMT) evaluations. Subclinical atherosclerosis indexes (CAC and C-IMT) were analyzed as dependent variables and migraine (all, with aura, without aura) as an independent variable in the linear and multinomial logistic regression models adjusted for possible confounders. Of 3217 ELSA participants free from CVD at baseline, we found a migraine frequency of 11.9% (5.1% with aura and 6.8% without aura). Overall, migraineurs were mostly women, younger and had lower frequency of CV risk factors, such as hypertension, diabetes and low HDL-cholesterol, compared to non-migraineurs. The strongest inverse correlation between migraine and subclinical atherosclerosis was verified with CAC score. However, all associations lost their significance after multivariate adjustment. In this cross-sectional evaluation of the ELSA study, migraine was not associated with subclinical atherosclerosis, regardless of aura symptoms. © International Headache Society 2015.

The cathelicidin protein CRAMP is a potential atherosclerosis self-antigen in ApoE(-/- mice.

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Peter M Mihailovic

Full Text Available Auto-immunity is believed to contribute to inflammation in atherosclerosis. The antimicrobial peptide LL-37, a fragment of the cathelicidin protein precursor hCAP18, was previously identified as an autoantigen in psoriasis. Given the reported link between psoriasis and coronary artery disease, the biological relevance of the autoantigen to atherosclerosis was tested in vitro using a truncated (t form of the mouse homolog of hCAP18, CRAMP, on splenocytes from athero-prone ApoE(-/- mice. Stimulation with tCRAMP resulted in increased CD8+ T cells with Central Memory and Effector Memory phenotypes in ApoE(-/- mice, differentially activated by feeding with normal chow or high fat diet. Immunization of ApoE(-/- with different doses of the shortened peptide (Cramp resulted in differential outcomes with a lower dose reducing atherosclerosis whereas a higher dose exacerbating the disease with increased neutrophil infiltration of the atherosclerotic plaques. Low dose Cramp immunization also resulted in increased splenic CD8+ T cell degranulation and reduced CD11b+CD11c+ conventional dendritic cells (cDCs, whereas high dose increased CD11b+CD11c+ cDCs. Our results identified CRAMP, the mouse homolog of hCAP-18, as a potential self-antigen involved in the immune response to atherosclerosis in the ApoE(-/- mouse model.

Who takes paternity leave? A cohort study on prior social and health characteristics among fathers in Stockholm.

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Månsdotter, Anna; Fredlund, Peeter; Hallqvist, Johan; Magnusson, Cecilia

2010-09-01

Progress towards gender equality involves changes in the traditional parental division - female caring and male breadwinning. One aspect is increased parental leave for fathers, which may benefit the health of mothers, children, and fathers themselves. We examined how social and health characteristics (2002) were associated with paternity leave in excess of the 'father quota' of 60 days (2003-2006) in the Stockholm Public Health Cohort. Generally, fathers with stable social position, fit lifestyles, and good health had increased chances of paternity leave uptake. Our findings may contribute to identifying target groups for parental leave strategies among fathers; they indicate also that research on gender equality and public health must carefully address the problems of confounding and health-related selection.

Prevalence and clinical characteristics of carotid atherosclerosis in newly diagnosed patients with ketosis-onset diabetes: a cross-sectional study

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2013-01-01

Background The features of carotid atherosclerosis in ketosis-onset diabetes have not been investigated. Our aim was to evaluate the prevalence and clinical characteristics of carotid atherosclerosis in newly diagnosed Chinese diabetic patients with ketosis but without islet-associated autoantibodies. Methods In total, 423 newly diagnosed Chinese patients with diabetes including 208 ketosis-onset diabetics without islet-associated autoantibodies, 215 non-ketotic type 2 diabetics and 79 control subjects without diabetes were studied. Carotid atherosclerosis was defined as the presence of atherosclerotic plaques in any of the carotid vessel segments. Carotid intima-media thickness (CIMT), carotid atherosclerotic plaque formation and stenosis were assessed and compared among the three groups based on Doppler ultrasound examination. The clinical features of carotid atherosclerotic lesions were analysed, and the risk factors associated with carotid atherosclerosis were evaluated using binary logistic regression in patients with diabetes. Results The prevalence of carotid atherosclerosis was significantly higher in the ketosis-onset diabetic group (30.80%) than in the control group (15.2%, p=0.020) after adjusting for age- and sex-related differences, but no significant difference was observed in comparison to the non-ketotic diabetic group (35.8%, p=0.487). The mean CIMT of the ketosis-onset diabetics (0.70±0.20 mm) was markedly higher than that of the control subjects (0.57±0.08 mm, pketosis-onset and the non-ketotic diabetes, the prevalence of carotid atherosclerosis was markedly increased with age (both pketosis-onset diabetics, the presence of carotid atherosclerosis was significantly associated with age, hypertension, low-density lipoprotein cholesterol and mean CIMT. Conclusions The prevalence and risk of carotid atherosclerosis were significantly higher in the ketosis-onset diabetics than in the control subjects but similar to that in the non-ketotic type 2

Induction of atherosclerosis in mice and hamsters without germline genetic engineering

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Bjørklund, Martin Mæng; Hollensen, Anne Kruse; Hagensen, Mette Kallestrup

2014-01-01

RATIONALE: Atherosclerosis can be achieved in animals by germline genetic engineering, leading to hypercholesterolemia, but such models are constrained to few species and strains, and they are difficult to combine with other powerful techniques involving genetic manipulation or variation. OBJECTIVE......: To develop a method for induction of atherosclerosis without germline genetic engineering. METHODS AND RESULTS: Recombinant adeno-associated viral vectors were engineered to encode gain-of-function proprotein convertase subtilisin/kexin type 9 mutants, and mice were given a single intravenous vector...... injection followed by high-fat diet feeding. Plasma proprotein convertase subtilisin/kexin type 9 and total cholesterol increased rapidly and were maintained at high levels, and after 12 weeks, mice had atherosclerotic lesions in the aorta. Histology of the aortic root showed progression of lesions...

A new multiple regression model to identify multi-family houses with a high prevalence of sick building symptoms "SBS", within the healthy sustainable house study in Stockholm (3H).

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Engvall, Karin; Hult, M; Corner, R; Lampa, E; Norbäck, D; Emenius, G

2010-01-01

The aim was to develop a new model to identify residential buildings with higher frequencies of "SBS" than expected, "risk buildings". In 2005, 481 multi-family buildings with 10,506 dwellings in Stockholm were studied by a new stratified random sampling. A standardised self-administered questionnaire was used to assess "SBS", atopy and personal factors. The response rate was 73%. Statistical analysis was performed by multiple logistic regressions. Dwellers owning their building reported less "SBS" than those renting. There was a strong relationship between socio-economic factors and ownership. The regression model, ended up with high explanatory values for age, gender, atopy and ownership. Applying our model, 9% of all residential buildings in Stockholm were classified as "risk buildings" with the highest proportion in houses built 1961-1975 (26%) and lowest in houses built 1985-1990 (4%). To identify "risk buildings", it is necessary to adjust for ownership and population characteristics.

Trajectories of neighborhood poverty and associations with subclinical atherosclerosis and associated risk factors: the multi-ethnic study of atherosclerosis.

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Murray, Emily T; Diez Roux, Ana V; Carnethon, Mercedes; Lutsey, Pamela L; Ni, Hanyu; O'Meara, Ellen S

2010-05-15

The authors used data from the Multi-Ethnic Study of Atherosclerosis and latent trajectory class modeling to determine patterns of neighborhood poverty over 20 years (1980-2000 residential history questionnaires were geocoded and linked to US Census data). Using these patterns, the authors examined 1) whether trajectories of neighborhood poverty were associated with differences in the amount of subclinical atherosclerosis (common carotid intimal-media thickness) and 2) associated risk factors (body mass index, hypertension, diabetes, current smoking) at baseline (January 2000-August 2002). The authors found evidence of 5 stable trajectory groups with differing levels of neighborhood poverty ( approximately 6%, 12%, 20%, 30%, and 45%) and 1 group with 29% poverty in 1980 and approximately 11% in 2000. Mostly for women, higher cumulative neighborhood poverty was generally significantly associated with worse cardiovascular outcomes. Trends generally persisted after adjustment for adulthood socioeconomic position and race/ethnicity, although they were no longer statistically significant. Among women who had moved during the 20 years, the long-term measure had stronger associations with outcomes (except smoking) than a single, contemporaneous measure. Results indicate that cumulative 20-year exposure to neighborhood poverty is associated with greater cardiovascular risk for women. In residentially mobile populations, single-point-in-time measures underestimate long-term effects.

Imaging Atherosclerosis with Hybrid Positron Emission Tomography/Magnetic Resonance Imaging

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Ripa, Rasmus Sejersten; Kjær, Andreas

2015-01-01

Noninvasive imaging of atherosclerosis could potentially move patient management towards individualized triage, treatment, and followup. The newly introduced combined positron emission tomography (PET) and magnetic resonance imaging (MRI) system could emerge as a key player in this context. Both...

Alcohol and atherosclerosis

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Murilo Foppa

2001-02-01

Full Text Available Observational studies have attributed a protective effect to alcohol consumption on the development of atherosclerosis and cardiovascular morbidity and mortality. Alcohol intake in the amount of one to two drinks per day results in an estimated 20-40% reduction in cardiovascular events. An additional protective effect, according to major cohort studies, has been attributed to wine, probably due to antioxidant effects and platelet antiaggregation agents. On the other hand, the influence of different patterns of alcohol consumption and environmental factors may explain a great part of the additional effect of wine. Protection may be mediated by modulation of other risk factors, because alcohol increases HDL-C, produces a biphasic response on blood pressure, and modulates the endothelial function, while it neither increases body weight nor impairs glucose-insulin homeostasis. Alcohol may also have a direct effect on atherogenesis. Despite these favorable effects, the current evidence is not enough to justify prescribing alcohol to prevent cardiovascular disease.

Apocynin suppresses the progression of atherosclerosis in apoE-deficient mice by inactivation of macrophages

International Nuclear Information System (INIS)

Kinoshita, Hiroyuki; Matsumura, Takeshi; Ishii, Norio; Fukuda, Kazuki; Senokuchi, Takafumi; Motoshima, Hiroyuki; Kondo, Tatsuya; Taketa, Kayo; Kawasaki, Shuji; Hanatani, Satoko; Takeya, Motohiro; Nishikawa, Takeshi; Araki, Eiichi

2013-01-01

Highlights: ► We examined the anti-athrogenic effect of apocynin in atherosclerotic model mice. ► Apocynin prevented atherosclerotic lesion formation. ► Apocynin suppressed ROS production in aorta and in macrophages. ► Apocynin suppressed cytokine expression and cell proliferation in macrophages. ► Apocynin may be beneficial compound for the prevention of atherosclerosis. -- Abstract: Production of reactive oxygen species (ROS) and other proinflammatory substances by macrophages plays an important role in atherogenesis. Apocynin (4-hydroxy-3-methoxy-acetophenone), which is well known as a NADPH oxidase inhibitor, has anti-inflammatory effects including suppression of the generation of ROS. However, the suppressive effects of apocynin on the progression of atherosclerosis are not clearly understood. Thus, we investigated anti-atherosclerotic effects of apocynin using apolipoprotein E-deficient (apoE –/– ) mice in vivo and in mouse peritoneal macrophages in vitro. In atherosclerosis-prone apoE –/– mice, apocynin suppressed the progression of atherosclerosis, decreased 4-hydroxynonenal-positive area in atherosclerotic lesions, and mRNA expression of monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) in aorta. In mouse peritoneal macrophages, apocynin suppressed the Ox-LDL-induced ROS generation, mRNA expression of MCP-1, IL-6 and granulocyte/macrophage colony-stimulating factor, and cell proliferation. Moreover, immunohistochemical studies revealed that apocynin decreased the number of proliferating cell nuclear antigen-positive macrophages in atherosclerotic lesions of apoE –/– mice. These results suggested that apocynin suppressed the formation of atherosclerotic lesions, at least in part, by inactivation of macrophages. Therefore, apocynin may be a potential therapeutic material to prevent the progression of atherosclerosis

Apocynin suppresses the progression of atherosclerosis in apoE-deficient mice by inactivation of macrophages

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Kinoshita, Hiroyuki [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan); Matsumura, Takeshi, E-mail: takeshim@gpo.kumamoto-u.ac.jp [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan); Ishii, Norio; Fukuda, Kazuki; Senokuchi, Takafumi; Motoshima, Hiroyuki; Kondo, Tatsuya; Taketa, Kayo; Kawasaki, Shuji; Hanatani, Satoko [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan); Takeya, Motohiro [Department of Cell Pathology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan); Nishikawa, Takeshi; Araki, Eiichi [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan)

2013-02-08

Highlights: ► We examined the anti-athrogenic effect of apocynin in atherosclerotic model mice. ► Apocynin prevented atherosclerotic lesion formation. ► Apocynin suppressed ROS production in aorta and in macrophages. ► Apocynin suppressed cytokine expression and cell proliferation in macrophages. ► Apocynin may be beneficial compound for the prevention of atherosclerosis. -- Abstract: Production of reactive oxygen species (ROS) and other proinflammatory substances by macrophages plays an important role in atherogenesis. Apocynin (4-hydroxy-3-methoxy-acetophenone), which is well known as a NADPH oxidase inhibitor, has anti-inflammatory effects including suppression of the generation of ROS. However, the suppressive effects of apocynin on the progression of atherosclerosis are not clearly understood. Thus, we investigated anti-atherosclerotic effects of apocynin using apolipoprotein E-deficient (apoE{sup –/–}) mice in vivo and in mouse peritoneal macrophages in vitro. In atherosclerosis-prone apoE{sup –/–} mice, apocynin suppressed the progression of atherosclerosis, decreased 4-hydroxynonenal-positive area in atherosclerotic lesions, and mRNA expression of monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) in aorta. In mouse peritoneal macrophages, apocynin suppressed the Ox-LDL-induced ROS generation, mRNA expression of MCP-1, IL-6 and granulocyte/macrophage colony-stimulating factor, and cell proliferation. Moreover, immunohistochemical studies revealed that apocynin decreased the number of proliferating cell nuclear antigen-positive macrophages in atherosclerotic lesions of apoE{sup –/–} mice. These results suggested that apocynin suppressed the formation of atherosclerotic lesions, at least in part, by inactivation of macrophages. Therefore, apocynin may be a potential therapeutic material to prevent the progression of atherosclerosis.

Epigenetic pathways in macrophages emerge as novel targets in atherosclerosis

NARCIS (Netherlands)

Neele, Annette E.; van den Bossche, Jan; Hoeksema, Marten A.; de Winther, Menno P. J.

2015-01-01

Atherosclerosis is a lipid-driven chronic inflammatory disorder. Monocytes and macrophages are key immune cells in the development of disease and clinical outcome. It is becoming increasingly clear that epigenetic pathways govern many aspects of monocyte and macrophage differentiation and

Relationship Between Lifelong Exercise Volume and Coronary Atherosclerosis in Athletes

NARCIS (Netherlands)

Aengevaeren, Vincent L; Mosterd, Arend; Braber, Thijs L; Prakken, Niek H J; Doevendans, Pieter A; Grobbee, Diederick E; Thompson, Paul D; Eijsvogels, Thijs M H; Velthuis, Birgitta K

2017-01-01

BACKGROUND: Higher levels of physical activity are associated with a lower risk of cardiovascular events. Nevertheless, there is debate on the dose-esponse relationship of exercise and cardiovascular disease outcomes and whether high volumes of exercise may accelerate coronary atherosclerosis. We

Understanding healthcare innovation systems: the Stockholm region case.

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Larisch, Lisa-Marie; Amer-Wåhlin, Isis; Hidefjäll, Patrik

2016-11-21

Purpose There is an increasing interest in understanding how innovation processes can address current challenges in healthcare. The purpose of this paper is to analyze the wider socio-economic context and conditions for such innovation processes in the Stockholm region, using the functional dynamics approach to innovation systems (ISs). Design/methodology/approach The analysis is based on triangulation using data from 16 in-depth interviews, two workshops, and additional documents. Using the functional dynamics approach, critical structural and functional components of the healthcare IS were analyzed. Findings The analysis revealed several mechanisms blocking innovation processes such as fragmentation, lack of clear leadership, as well as insufficient involvement of patients and healthcare professionals. Furthermore, innovation is expected to occur linearly as a result of research. Restrictive rules for collaboration with industry, reimbursement, and procurement mechanisms limit entrepreneurial experimentation, commercialization, and spread of innovations. Research limitations/implications In this study, the authors analyzed how certain functions of the functional dynamics approach to ISs related to each other. The authors grouped knowledge creation, resource mobilization, and legitimacy as they jointly constitute conditions for needs articulation and entrepreneurial experimentation. The economic effects of entrepreneurial experimentation and needs articulation are mainly determined by the stage of market formation and existence of positive externalities. Social implications Stronger user involvement; a joint innovation strategy for healthcare, academia, and industry; and institutional reform are necessary to remove blocking mechanisms that today prevent innovation from occurring. Originality/value This study is the first to provide an analysis of the system of innovation in healthcare using a functional dynamics approach, which has evolved as a tool for public

Comparison of osteoprotegerin to traditional atherosclerotic risk factors and high-sensitivity C-reactive protein for diagnosis of atherosclerosis

DEFF Research Database (Denmark)

Mogelvang, Rasmus; Pedersen, Sune Holm; Flyvbjerg, Allan

2012-01-01

Atherosclerosis is the main cause of cardiovascular disease, but the extent of atherosclerosis in individual patients is difficult to estimate. A biomarker of the atherosclerotic burden would be very valuable. The aim of the present study was to evaluate the association of plasma osteoprotegerin ...

Sensitization of children in the Stockholm area to house dust mites.

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Nordvall, S L; Eriksson, M; Rylander, E; Schwartz, B

1988-09-01

Atopic sensitization of children in the Stockholm area to house dust mites (HDM) was investigated in a case-control study. Sixty children with and 60 without positive skin prick tests for HDM were matched for age and sex. HDM-sensitized children had previously more often lived in other areas known to be mite infested than the control children. Sensitization to mites was related to dampness in the homes, but no significant relationship was found to the type of residence, frequent visits to a summer house in the archipelago or parental smoking. Dust samples from mattresses of the children with the strongest positive reactions to mites in skin prick tests and the respective controls were subjected to an enzyme immunoassay, to measure the content of the major allergens of the Dermatophagoides (D.) species D. pterinyssinus, D. farinae and D. microceras. Mattress dust samples from the beds of HDM-sensitized children contained significantly higher HDM antigen concentrations than those from the beds of controls. Private houses contained significantly more HDM antigens than flats and 10 of 11 homes in which a dampness problem was recognized contained mite antigens. It is postulated that mite infestation is increasing in the area, energy-saving measures creating improved conditions for HDM survival.

L-arginine prevents xanthoma development and inhibits atherosclerosis in LDL receptor knockout mice.

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Aji, W; Ravalli, S; Szabolcs, M; Jiang, X C; Sciacca, R R; Michler, R E; Cannon, P J

1997-01-21

The potential antiatherosclerotic actions of NO were investigated in four groups of mice (n = 10 per group) lacking functional LDL receptor genes, an animal model of familial hypercholesterolemia. Group 1 was fed a regular chow diet. Groups 2 through 4 were fed a 1.25% high-cholesterol diet. In addition, group 3 received supplemental L-arginine and group 4 received L-arginine and N omega-nitro-L-arginine (L-NA), an inhibitor of NO synthase (NOS). Animals were killed at 6 months; aortas were stained with oil red O for planimetry and with antibodies against constitutive and inducible NOSs. Plasma cholesterol was markedly increased in the animals receiving the high-cholesterol diet. Xanthomas appeared in all mice fed the high-cholesterol diet alone but not in those receiving L-arginine. Aortic atherosclerosis was present in all mice on the high-cholesterol diet. The mean atherosclerotic lesion area was reduced significantly (P < .01) in the cholesterol-fed mice given L-arginine compared with those receiving the high-cholesterol diet alone. The mean atherosclerotic lesion area was significantly larger (P < .01) in cholesterol-fed mice receiving L-arginine + L-NA than in those on the high-cholesterol diet alone. Within the atherosclerotic plaques, endothelial cells immunoreacted for endothelial cell NOS; macrophages, foam cells, and smooth muscle cells immunostained strongly for inducible NOS and nitrotyrosine residues. The data indicate that L-arginine prevents xanthoma formation and reduces atherosclerosis in LDL receptor knockout mice fed a high-cholesterol diet. The abrogation of the beneficial effects of L-arginine by L-NA suggests that the antiatherosclerotic actions of L-arginine are mediated by NOS. The data suggest that L-arginine may be beneficial in familial hypercholesterolemia.

A Role of RIP3-Mediated Macrophage Necrosis in Atherosclerosis Development

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Juan Lin

2013-01-01

Full Text Available Necrotic death of macrophages has long been known to be present in atherosclerotic lesions but has not been studied. We examined the role of receptor interacting protein (RIP 3, a mediator of necrotic cell death, in atherosclerosis and found that RIP3−/−;Ldlr−/− mice were no different from RIP3+/+;Ldlr−/− mice in early atherosclerosis but had significant reduction in advanced atherosclerotic lesions. Similar results were observed in Apoe−/− background mice. Bone marrow transplantation revealed that loss of RIP3 expression from bone-marrow-derived cells is responsible for the reduced disease progression. While no difference was found in apoptosis between RIP3−/−;Ldlr−/− and RIP3+/+;Ldlr−/− mice, electron microscopy revealed a significant reduction of macrophage primary necrosis in the advanced lesions of RIP3−/− mice. In vitro cellular studies showed that RIP3 deletion had no effect on oxidized low-density lipoprotein (LDL-induced macrophage apoptosis, but prevented macrophage primary necrosis occurring in response to oxidized LDL under caspase inhibition or RIP3 overexpression conditions. RIP3-dependent necrosis is not postapoptotic, and the increased primary necrosis in advanced atherosclerotic lesions most likely resulted from the increase of RIP3 expression. Our data demonstrate that primary necrosis of macrophages is proatherogenic during advanced atherosclerosis development.

Curcumin Protects against Atherosclerosis in Apolipoprotein E-Knockout Mice by Inhibiting Toll-like Receptor 4 Expression.

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Zhang, Shanshan; Zou, Jun; Li, Peiyang; Zheng, Xiumei; Feng, Dan

2018-01-17

Toll-like receptor 4 (TLR4) has been reported to play a critical role in the pathogenesis of atherosclerosis, the current study aimed to investigate whether curcumin suppresses atherosclerosis development in ApoE-knockout (ApoE -/- ) mice by inhibiting TLR4 expression. ApoE -/- mice were fed a high-fat diet supplemented with or without curcumin (0.1% w/w) for 16 weeks. Curcumin supplementation significantly reduced TLR4 expression and macrophage infiltration in atherosclerotic plaques. Curcumin also reduced aortic interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) expression, nuclear factor-κB (NF-κB) activity, and plasma IL-1β, TNF-α, soluble VCAM-1 and ICAM-1 levels. In addition, aortic sinus sections revealed that curcumin treatment reduced the extent of atherosclerotic lesions and inhibited atherosclerosis development. In vitro, curcumin inhibited NF-κB activation in macrophages and reduced TLR4 expression induced by lipopolysaccharide. Our results indicate that curcumin protects against atherosclerosis at least partially by inhibiting TLR4 expression and its related inflammatory reaction.

[Prevalence and risk factors of extra-coronary artery disease in patients with diabetes which confirmed atherosclerosis of coronary arteries].

Science.gov (United States)

Gracheva, S A; Biragova, M S; Glazunova, A M; Klefortova, I I; Melkozerov, K V; Shamkhalova, M Sh; Dzhavelidze, M I; Soldatova, T V; Il'in, A V; Deev, A D; Shestakova, M V; Tugeeva, E F; Buziashvili, Iu I

2014-01-01

To assess prevalence and risk factors of extra-coronary artery disease (peripheral artery (PA) disease (D) of lower extremities (LE), brachiocephalic arterial (BCA) stenosis (S), renal arterial (RA) S in type 1 and 2 (T1 and T2) diabetes (D) patients (P) with confirmed atherosclerosis of coronary arteries (CA). 100 P (48 with T2D, 18 with T1D, 34 without diabetes - PWD), with hemodynamically significant atherosclerosis of CA confirmed by coronary angiography. All patients underwent duplex ultrasonography of PA LE, BCA, RA. Other studies included assessment of clinical characteristics and measurement of the following parameters: profibrogenic cytokines (transforming growth factor [TGF] beta1, matrix metalloproteinase 9 [MMP9], monocyte chemotactic protein-1 [MCP-1], regulated on activation normal T-cell expressed and secreted [RANTES), markers of endothelial dysfunction (von Willebrand factor [VWF], homocystein [HCYST], plasminogen activator inhibitor-1 [PAI-1], vascular cell adhesion molecule [VCAM], soluble intercellular adhesion molecules-1 [sICAM], vascular endothelial growth factor [VEGF], asymmetric dimethylarginine [ADMAD, N-terminal fragment of pro-brain natriuretic peptide (NT-pro BNP), fibroblast growth factor 23 (FGF-23), and fibrinogen. Portions of P with multivessel CA disease were similar in all three groups (T1D - 88.9, T2D - 85.5, WD - 82.3%). Coexistence of atherosclerosis in 2 or more vascular beds was identified in 85.3% of T2D and in 50% of WD P (p = 0.005). In T1D group 61.1 and 11.1% of P had atherosclerosis in 2 and 3 vascular beds, respectively. Levels of profibrogenic cytokines and factors of endothelial activation (RANTES, MMP-9, PAI-I, VCAM, sICAM, ADMA) were significantly higher in P with diabetes vs P WD. P with diabetes and multifocal atherosclerosis demonstrated significant increases of CRP, fibrinogen, NT-proBNP, VWF, PAI-1, ADMA, sICAM, and decrease of GFR compared with P with atherosclerosis in 1 vascular bed. Logistic regression

Telomere Length and the Cancer-Atherosclerosis Trade-Off.

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Rivka C Stone

2016-07-01

Full Text Available Modern humans, the longest-living terrestrial mammals, display short telomeres and repressed telomerase activity in somatic tissues compared with most short-living small mammals. The dual trait of short telomeres and repressed telomerase might render humans relatively resistant to cancer compared with short-living small mammals. However, the trade-off for cancer resistance is ostensibly increased age-related degenerative diseases, principally in the form of atherosclerosis. In this communication, we discuss (a the genetics of human telomere length, a highly heritable complex trait that is influenced by genetic ancestry, sex, and paternal age at conception, (b how cancer might have played a role in the evolution of telomere biology across mammals, (c evidence that in modern humans telomere length is a determinant (rather than only a biomarker of cancer and atherosclerosis, and (d the potential influence of relatively recent evolutionary forces in fashioning the variation in telomere length across and within populations, and their likely lasting impact on major diseases in humans. Finally, we propose venues for future research on human telomere genetics in the context of its potential role in shaping the modern human lifespan.

The monocytic lineage specific soluble CD163 is a plasma marker of coronary atherosclerosis

DEFF Research Database (Denmark)

Aristoteli, Lina Panayiota; Møller, Holger Jon; Bailey, Brian

2006-01-01

BACKGROUND: CD163 is a monocyte-macrophage lineage specific scavenger receptor that mediates the uptake and clearance of haptoglobin-haemoglobin complexes, and soluble CD163 (sCD163) is also present in plasma. As atherosclerosis involves infiltration by monocyte-derived macrophages, we investigated...... whether sCD163 may act as a marker of coronary atherosclerosis (CAD). METHODS AND RESULTS: Clinical features were identified and plasma was collected from 147 consecutive patients presenting for coronary angiography. Patients were classified as having CAD+, or being free of CAD- haemodynamically...

Inhibitory effects of myricitrin on oxidative stress-induced endothelial damage and early atherosclerosis in ApoE −/− mice

International Nuclear Information System (INIS)

Sun, Gui-bo; Qin, Meng; Ye, Jing-xue; Pan, Rui-le; Meng, Xiang-bao; Wang, Min; Luo, Yun; Li, Zong-yang; Wang, Hong-wei; Sun, Xiao-bo

2013-01-01

Atherosclerosis (AS) is a state of heightened oxidative stress characterized by lipid and protein oxidation in vascular walls. Oxidative stress-induced vascular endothelial cell (VEC) injury is a major factor in the pathogenesis of AS. Myricitrin, a natural flavonoid isolated from the root bark of Myrica cerifera, was recently found to have a strong antioxidative effect. However, its use for treating cardiovascular diseases, especially AS is still unreported. Consequently, we evaluated the cytoprotective effect of myricitrin on AS by assessing oxidative stress-induced VEC damage. The in vivo study using an ApoE −/− mouse model of AS demonstrated that myricitrin treatment protects against VEC damage and inhibits early AS plaque formation. This effect is associated with the antioxidative effect of myricitrin, as observed in a hydrogen peroxide (H 2 O 2 )-induced rat model of artery endothelial injury and primary cultured human VECs. Myricitrin treatment also prevents and attenuates H 2 O 2 -induced endothelial injury. Further investigation of the cytoprotective effects of myricitrin demonstrated that myricitrin exerts its function by scavenging for reactive oxygen species, as well as reducing lipid peroxidation, blocking NO release, and maintaining mitochondrial transmembrane potential. Myricitrin treatment also significantly decreased H 2 O 2 -induced apoptosis in VECs, which was associated with significant inhibition of p53 gene expression, activation of caspase-3 and the MAPK signaling pathway, and alteration of the patterns of pro-apoptotic and anti-apoptotic gene expression. The resulting significantly increased bcl-2/bax ratio indicates that myricitrin may prevent the apoptosis induced by oxidative stress injury. - Highlights: • Myricitrin prevents early atherosclerosis in ApoE−/− mice. • Myricitrin protects endothelial cell from H 2 O 2 induced injury in rat and HUVECs. • Myricitrin enhanced NO release and up regulates eNOS activity in HUVECs. �

PPARα activation differently affects microparticle content in atherosclerotic lesions and liver of a mouse model of atherosclerosis and NASH.

Science.gov (United States)

Baron, Morgane; Leroyer, Aurélie S; Majd, Zouher; Lalloyer, Fanny; Vallez, Emmanuelle; Bantubungi, Kadiombo; Chinetti-Gbaguidi, Giulia; Delerive, Philippe; Boulanger, Chantal M; Staels, Bart; Tailleux, Anne

2011-09-01

Atherosclerosis and non-alcoholic fatty liver disease (NAFLD) are complex pathologies characterized by lipid accumulation, chronic inflammation and extensive tissue remodelling. Microparticles (MPs), small membrane vesicles produced by activated and apoptotic cells, might not only be biomarkers, but also functional actors in these pathologies. The apoE2-KI mouse is a model of atherosclerosis and NAFLD. Activation of the nuclear receptor PPARα decreases atherosclerosis and components of non-alcoholic steatohepatitis (NASH) in the apoE2-KI mouse. (1) To determine whether MPs are present in atherosclerotic lesions, liver and plasma during atherosclerosis and NASH progression in apoE2-KI mice, and (2) to study whether PPARα activation modulates MP concentrations. ApoE2-KI mice were fed a Western diet to induce atherosclerosis and NASH. MPs were isolated from atherosclerotic lesions, liver and blood and quantified by flow cytometry. An increase of MPs was observed in the atherosclerotic lesions and in the liver of apoE2-KI mice upon Western diet feeding. PPARα activation with fenofibrate decreased MP levels in the atherosclerotic lesions in a PPARα-dependent manner, but did not influence MP concentrations in the liver. Here we report that MPs are present in atherosclerotic lesions and in the liver of apoE2-KI mice. Their concentration increased during atherosclerosis and NASH development. PPARα activation differentially modulates MP levels in a tissue-specific manner. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Depressive and anxiety disorders and risk of subclinical atherosclerosis Findings from the Netherlands Study of Depression and Anxiety (NESDA)

NARCIS (Netherlands)

Seldenrijk, Adrie; Vogelzangs, Nicole; van Hout, Hein P. J.; van Marwijk, Harm W. J.; Diamant, Michaela; Penninx, Brenda W. J. H.

Objective: Current evidence regarding the association between psychopathology and subclinical atherosclerosis show inconsistent results. The present study examined whether subclinical atherosclerosis was more prevalent in a large cohort of persons with depressive or anxiety disorders as compared to

Moderate beer consumption does not change early or mature atherosclerosis in mice

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Blanco-Vaca Francisco

2004-01-01

Full Text Available Abstract Background Although the consumption of wine in particular has been associated with a lower risk of atherothrombotic cardiovascular disease, systematic reviews differ as to the relative protective effect of beer, wine and spirits. Two previous studies showed that red wine reduces fatty streak formation (early atherosclerosis but not mature atherosclerosis in apolipoprotein (apo E-deficient (apoE-/- mice. Aim of the study To determine whether a moderate beer intake would affect early and mature atherosclerotic lesion formation using control C57BL/6 and apoE-/- mice, respectively, as models. Methods Control C57BL/6 and apoE-/- mice were randomized to receive either water, ethanol, mild beer, dark beer or ethanol-free beer. The level of beer was designed to approximate the alcohol intake currently believed to be beneficial in reducing human vascular risk. Control C57BL/6 mice were fed a Western diet for 24 weeks, and apoE-/- mice a chow diet for 12 weeks. At the end of the trial period, mice were euthanized and atherosclerotic lesions quantified. Plasma lipid concentrations were also measured. Results The amount of atherosclerosis and average number of lesions in the proximal aortic region did not differ among groups in control C57BL/6 mice (p = 0.32 and p = 0.29, respectively and apoE-/- mice (p = 0.19 and p = 0.59, respectively. No consistent differences were observed in plasma lipid and lipoprotein concentrations among water, ethanol and beer groups. Conclusions Moderate beer consumption does not change the development of early or mature atherosclerosis in mice. Our findings do not support the hypothesis of an anti-atherogenic effect of beer. Other potential protective actions of moderate beer consumption such as plaque stabilization, a reduction in plaque intrinsic thrombogenicity, or a reduction in the systemic propensity to thrombosis, remain to be studied.

Dietary patterns, biomarkers of atherosclerosis, cardiovascular and all-cause mortality

NARCIS (Netherlands)

Sijtsma, F.P.C.

2015-01-01

Summary belonging to the thesis entitled ‘Dietary patterns, biomarkers of atherosclerosis, cardiovascular and all-cause mortality’

The long history of epidemiologic studies on diet and cardiovascular disease (CVD) has traditionally relied on analysis of specific nutrients

Nitro-fatty acids reduce atherosclerosis in apolipoprotein E-deficient mice

Czech Academy of Sciences Publication Activity Database

Rudolph, T.K.; Rudolph, V.; Edreira, M.M.; Cole, M.P.; Bonacci, G.; Schopfer, F.J.; Woodcock, S.R.; Franek, A.; Pekarová, Michaela; Khoo, N.K.H.; Hasty, A.H.; Baldus, S.; Freeman, B.A.

2010-01-01

Roč. 30, č. 5 (2010), s. 938-945 ISSN 1079-5642 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : nitro-fatty acids * atherosclerosis * foam cells Subject RIV: BO - Biophysics Impact factor: 7.215, year: 2010

Cyclodextrin promotes atherosclerosis regression via macrophage reprogramming

DEFF Research Database (Denmark)

Zimmer, Sebastian; Grebe, Alena; Bakke, Siril S

2016-01-01

-containing lipoproteins in the subendothelial space causes a local overabundance of free cholesterol. Because cholesterol accumulation and deposition of cholesterol crystals (CCs) trigger a complex inflammatory response, we tested the efficacy of the cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (CD), a compound...... of CD as well as for augmented reverse cholesterol transport. Because CD treatment in humans is safe and CD beneficially affects key mechanisms of atherogenesis, it may therefore be used clinically to prevent or treat human atherosclerosis....

Ankle brachial index, C-reactive protein, and central augmentation index to identify individuals with severe atherosclerosis

DEFF Research Database (Denmark)

Eldrup, Nikolaj; Sillesen, Henrik; Prescott, Eva

2006-01-01

We examined the ability of ankle brachial index, C-reactive protein and central augmentation index to identify individuals in the general population with severe atherosclerosis, diagnosed as those with ischaemic cardiovascular disease.......We examined the ability of ankle brachial index, C-reactive protein and central augmentation index to identify individuals in the general population with severe atherosclerosis, diagnosed as those with ischaemic cardiovascular disease....

Prevention of atherosclerosis by specific AT1-receptor blockade with candesartan cilexetil

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Vasilios Papademetriou

2001-03-01

Full Text Available Several studies indicate that blockade of the renin-angiotensin-aldosterone system (RAAS can prevent atherosclerosis and vascular events, but the precise mechanisms involved are still unclear. In this study, we investigated the effect of the AT 1-receptor blocker, candesartan, in the prevention of atherosclerosis in Watanabe heritable hyperlipidaemic (WHHL rabbits and also the effect of AT1-receptor blockade in the uptake of oxidised LDL by macrophage cell cultures. In the first set of experiments, 12 WHHL rabbits were randomly assigned to three groups: placebo, atenolol 5 mg/kg daily or candesartan 2 mg/kg daily for six months. Compared with controls and atenolol-treated rabbits, candesartan treatment resulted in a significant 50—60% reduction of atherosclerotic plaque formation and a 66% reduction in cholesterol accumulation in the thoracic aorta.Studies in macrophage cultures indicated that candesartan prevented uptake of oxidised LDL-(oxLDL-cholesterol by cultured macrophages. Candesartan inhibited the uptake of oxLDL in a dose-dependent manner, reaching a maximum inhibition of 70% at concentrations of 5.6 µg/ml. Further studies in other animal models and well-designed trials in humans are warranted to further explore the role of AT1-receptor blockade in the prevention of atherosclerosis.

The Establishment and Characteristics of Rat Model of Atherosclerosis Induced by Hyperuricemia

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Zhen Liu

2016-01-01

Full Text Available Epidemiological studies have identified hyperuricemia as an independent risk factor for cardiovascular disease. However, the mechanism whereby hyperuricemia causes atherosclerosis remains unclear. The objective of the study was to establish a new rat model of hyperuricemia-induced atherosclerosis. Wistar-Kyoto rats were randomly allocated to either a normal diet (ND, high-fat diet (HFD, or high-adenine diet (HAD, followed by sacrifice 4, 8, or 12 weeks later. Serum uric acid and lipid levels were analyzed, pathologic changes in the aorta were observed by hematoxylin and eosin staining, and mRNA expression was evaluated by quantitative real-time polymerase chain reaction. Serum uric acid and TC were significantly increased in the HAD group at 4 weeks compared with the ND group, but there was no significant difference in serum uric acid between the ND and HFD groups. Aorta calcification occurred earlier and was more severe in the HAD group, compared with the HFD group. Proliferating cell nuclear antigen, monocyte chemotactic factor-1, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 mRNA levels were increased in the HFD and HAD groups compared with the ND group. This new animal model will be a useful tool for investigating the mechanisms responsible for hyperuricemia-induced atherosclerosis.

Role of the Vasa Vasorum and Vascular Resident Stem Cells in Atherosclerosis

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Jun-ichi Kawabe

2014-01-01

Full Text Available Atherosclerosis is considered an “inside-out” response, that begins with the dysfunction of intimal endothelial cells and leads to neointimal plaque formation. The adventitia of large blood vessels has been recognized as an active part of the vessel wall that is involved in the process of atherosclerosis. There are characteristic changes in the adventitial vasa vasorum that are associated with the development of atheromatous plaques. However, whether vasa vasorum plays a causative or merely reactive role in the atherosclerotic process is not completely clear. Recent studies report that the vascular wall contains a number of stem/progenitor cells that may contribute to vascular remodeling. Microvessels serve as the vascular niche that maintains the resident stem/progenitor cells of the tissue. Therefore, the vasa vasorum may contribute to vascular remodeling through not only its conventional function as a blood conducting tube, but also its new conceptual function as a stem cell reservoir. This brief review highlights the recent advances contributing to our understanding of the role of the adventitial vasa vasorum in the atherosclerosis and discusses new concept that involves vascular-resident factors, the vasa vasorum and its associated vascular-resident stem cells, in the atherosclerotic process.

Lower zinc bioavailability may be related to higher risk of subclinical atherosclerosis in Korean adults.

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Su Kyoung Jung

Full Text Available BACKGROUND: There is a proposed link between dietary zinc intake and atherosclerosis, but this relationship remains unclear. Phytate may contribute to this relationship by influencing zinc bioavailability. OBJECTIVE: The aim of this study is to examine the relationship between zinc bioavailability and subclinical atherosclerosis in healthy Korean adults. MATERIALS AND METHODS: The present cross-sectional analysis used baseline data from the Korean multi-Rural Communities Cohort Study (MRCohort, which is a part of The Korean Genome Epidemiology Study (KoGES. A total of 5,532 subjects (2,116 men and 3,416 women aged 40 years and older were recruited from rural communities in South Korea between 2005 and 2010. Phytate:zinc molar ratio, estimated from a food-based food frequency questionnaire (FFQ of 106 food items, was used to determine zinc bioavailability, and carotid intima media thickness (cIMT and pulse wave velocity (PWV were measured to calculate the subclinical atherosclerotic index. RESULTS: We found that phytate:zinc molar ratio is positively related to cIMT in men. A higher phytate:zinc molar ratio was significantly related to an increased risk of atherosclerosis in men, defined as the 80(th percentile value of cIMT (5(th vs. 1(st quintile, OR = 2.11, 95% CI 1.42-3.15, P for trend = 0.0009, and especially in elderly men (5(th vs. 1(st quintile, OR = 2.58, 95% CI 1.52-4.37, P for trend = 0.0021. We found a positive relationship between phytate:zinc molar ratio and atherosclerosis risk among women aged 65 years or younger. Phytate:zinc molar ratio was not found to be related to PWV. CONCLUSIONS: Lower zinc bioavailability may be related to higher atherosclerosis risk.

Parity and carotid atherosclerosis in men and women: insights into the roles of childbearing and child-rearing.

Science.gov (United States)

Skilton, Michael R; Sérusclat, André; Begg, Lisa M; Moulin, Philippe; Bonnet, Fabrice

2009-04-01

Parity appears to be associated with carotid atherosclerosis in women aged 45 years and older. Studying this association among younger women and men may provide insight into whether this association relates predominantly to childbearing or child-rearing. The association between parity and carotid atherosclerosis (intima-media thickness and presence of plaques) was assessed in a cohort consisting of 750 women and 1164 men, all with at least one traditional cardiovascular risk factor, aged 18 to 80 years of age. Traditional cardiovascular risk factors were also assessed, and the Framingham Risk Score calculated. In age-adjusted analyses, the number of children was associated with adiposity, fasting glucose, 2-hour glucose, Framingham risk score, and carotid atherosclerosis in women, but not in men. Multivariate linear regression models indicate that the prevalence of plaques was increased by 15% (95% CI, 2 to 29) per child among women, and 0% (95% CI, -10 to 11) among men, after adjustment for age, socioeconomic and lifestyle factors (including waist circumference). The association between parity and carotid intima-media thickness was similar in younger and older women (P(Heterogeneity)=0.20). A higher number of children is associated with increased carotid atherosclerosis in both younger and older women, but not among men. These findings indicate that childbearing, but not child-rearing, may be a risk factor for atherosclerosis, and suggest the potential importance of considering the number of children when assessing the level of cardiovascular risk in women.

[Macrophage activation in atherosclerosis. Message 1: Activation of macrophages normally and in atherosclerotic lesions].

Science.gov (United States)

Nikiforov, N G; Kornienko, V Y; Karagodin, V P; Orekhov, A N

2015-01-01

Macrophages play important role in initiation and progression of inflammation in atherosclerosis. Plaque macrophages were shown to exhibit a phenotypic range that is intermediate between two extremes, M1 (proinflammatory) and M2 (anti-inflammatory). Indeed, in atherosclerosis, macrophages demonstrate phenotypic plasticity to rapidly adjust to changing microenvironmental conditions. In plaque macrophages demonstrate different phenotypes, and besides macrophage phenotypes could be changed. Phenotypes M1, M2, M4, Mhem, HA-mac, M(Hb) u Mox are described in the article. Ability of macrophages change their phenotype also considered.

NMR imaging of human atherosclerosis

International Nuclear Information System (INIS)

Toussaint, J.F.

1995-01-01

Diagnosis and prognosis of atherosclerosis can no longer be evaluated with morphological parameters only. A description of atherosclerotic plaque composition is necessary to study the mechanisms of plaque rupture, which depends on collagenous cap and lipid core thicknesses. NMR, as a biochemical imaging technique, allows visualization of these components using T1 contrast (mobile lipids), T2 contrast (cap vs. core), spin density (calcifications), diffusion imaging, 1H and 13C spectroscopy. Today, these imaging sequences allow to study in vitro the effects of interventional techniques such as angioplasty or atherectomy. Clinical investigations begin, which will attempt to develop in vivo microscopy and test the ability of NMR to predict plaque rupture. (author). 13 refs., 7 figs

Mechanisms of foam cell formation in atherosclerosis.

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Chistiakov, Dimitry A; Melnichenko, Alexandra A; Myasoedova, Veronika A; Grechko, Andrey V; Orekhov, Alexander N

2017-11-01

Low-density lipoprotein (LDL) and cholesterol homeostasis in the peripheral blood is maintained by specialized cells, such as macrophages. Macrophages express a variety of scavenger receptors (SR) that interact with lipoproteins, including SR-A1, CD36, and lectin-like oxLDL receptor-1 (LOX-1). These cells also have several cholesterol transporters, including ATP-binding cassette transporter ABCA1, ABCG1, and SR-BI, that are involved in reverse cholesterol transport. Lipids internalized by phagocytosis are transported to late endosomes/lysosomes, where lysosomal acid lipase (LAL) digests cholesteryl esters releasing free cholesterol. Free cholesterol in turn is processed by acetyl-CoA acetyltransferase (ACAT1), an enzyme that transforms cholesterol to cholesteryl esters. The endoplasmic reticulum serves as a depot for maintaining newly synthesized cholesteryl esters that can be processed by neutral cholesterol ester hydrolase (NCEH), which generates free cholesterol that can exit via cholesterol transporters. In atherosclerosis, pro-inflammatory stimuli upregulate expression of scavenger receptors, especially LOX-1, and downregulate expression of cholesterol transporters. ACAT1 is also increased, while NCEH expression is reduced. This results in deposition of free and esterified cholesterol in macrophages and generation of foam cells. Moreover, other cell types, such as endothelial (ECs) and vascular smooth muscle cells (VSMCs), can also become foam cells. In this review, we discuss known pathways of foam cell formation in atherosclerosis.

The impact of splenectomy on human coronary artery atherosclerosis and vascular macrophage distribution.

Science.gov (United States)

Li, Yu; Stone, James R

Splenectomy can potentially impact atherosclerosis through multiple mechanisms including altered lipid homeostasis, increased coagulation, and altered macrophage recruitment to the plaque. In patients, splenectomy has been associated with increased rates of coronary artery events, while in experimental mice, splenectomy causes increased atherosclerosis but reduces systemic monocyte supply. In this study, the direct impact of splenectomy on human coronary artery atherosclerotic plaque severity and macrophage content was investigated. Coronary artery atherosclerotic plaque severity was determined at autopsy in 18 long-term (≥10 years) splenectomy patients and 90 matched control patients. Coronary artery macrophage content was evaluated in mild atherosclerotic plaques of 11 mid- to long-term (≥1 year) splenectomy patients and 11 matched control patients. Splenectomy was associated with reduced coronary artery atherosclerosis (P=.03). The association was most pronounced for the subgroup of patients who had undergone splenectomy 20 years or more prior to death (P=.02). There was no difference in the density of macrophages in the plaque, media, or adventitia upon comparing splenectomy and control patients. In the control group, there was no correlation between the macrophage densities in the three arterial layers. However, in the splenectomy patients, there was a strong correlation in the macrophage densities across the plaque, media, and adventitia (P≤.0002), with resulting slopes that were significantly greater than seen in the control patients (P=.0007-.011). These findings indicate that, in humans, splenectomy is associated with lower coronary artery atherosclerotic plaque severity and altered coronary artery macrophage distribution. These results suggest that the spleen can modulate the recruitment of macrophages into human coronary arteries and the progression of atherosclerosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Association of insomnia and short sleep duration with atherosclerosis risk in the elderly.

Science.gov (United States)

Nakazaki, Chie; Noda, Akiko; Koike, Yasuo; Yamada, Sumio; Murohara, Toyoaki; Ozaki, Norio

2012-11-01

Short sleep duration is associated with an increased risk of cardiovascular disease and all-cause mortality, although a relationship with atherosclerosis in the elderly remains unclear. Eighty-six volunteers aged ≥65 years (mean, 73.6 ± 4.9 years) were evaluated for insomnia. Total sleep time (TST) and sleep efficiency were measured by actigraphy. Subjective symptoms were assessed with the Pittsburgh Sleep Quality Index (PSQI). Atherosclerosis was evaluated using ultrasonographic measurements of carotid intima-media thickness (IMT). IMT was significantly greater and sleep efficiency was significantly lower in subjects with TST ≤5 h than those with TST >7 h (1.3 ± 0.5 vs. 0.9 ± 0.3 mm; P = 0.009; 91.0 ± 6.0 vs. 81.6 ± 11.3%, P = 0.03, respectively). IMT was also significantly greater in the insomnia group than the noninsomnia group (1.3 ± 0.5 vs. 1.1 ± 0.4 mm; P = 0.03). IMT was significantly correlated with systolic blood pressure (SBP), diastolic blood pressure (DBP), and TST (SBP: r = 0.49, P insomnia were associated with atherosclerosis risk leading to cardiovascular disease in the elderly.

The effectiveness of chemical carcinogens to induce atherosclerosis in the white carneau pigeon

International Nuclear Information System (INIS)

Revis, N.W.; Bull, R.; Laurie, D.; Schiller, C.A.

1984-01-01

The frequency of atherosclerotic lesions of the abdominal aorta has been reported to increase significantly in chickens exposed to benzo(a)pyrene and 7,12-dimethylbenz(a,h)anthracene. The present studies were performed to determine in another experimental model frequently used in atherosclerotic studies (i.e. White Carneau Pigeons) whether these and other chemical carcinogens enhance atherosclerosis. The induction and enhancement of atherosclerotic lesions were observed in pigeons treated with 7,12-dimethylbenz(a,h)anthracene, benzo(a)pyrene and 3-methylcholanthrene. The number and size of plaques in the aorta were frequently greater in pigeons treated with the higher concentrations (i.e. 100 mg/kg) of these 3 polycyclic aromatic hydrocarbons. Benzo(e)pyrene and 2,4,6-trichlorophenol were ineffective in the induction or enhancement of atherosclerosis in the pigeons. The results of the present and previous studies suggest that the polycyclic aromatic hydrocarbons (excluding benzo(e)pyrene) may be the only potential atherogens in avian atherosclerosis. This relationship may be associated with how these hydrocarbons are transported in the plasma (i.e. by lipoproteins) as demonstrated by the present distribution studies (author)

Risk of self-reported Chlamydia trachomatis infection by social and lifestyle factors: a study based on survey data from young adults in Stockholm, Sweden.

Science.gov (United States)

Deogan, Charlotte; Cnattingius, Sven; Månsdotter, Anna

2012-12-01

To analyse the associations between demographic, socio-economic and lifestyle factors, and the risk of self-reported chlamydial infection among young adults (20-29 years old) in Stockholm, Sweden. This study was based on the Stockholm Public Health Survey of 2006 (N = 4278). Demographic factors (gender, age, and country of birth), socio-economic factors (individual and parental educational levels, individual income level, and employment status), and lifestyle factors (body mass index, mental health, alcohol consumption, and partnership status) were taken into account. Possible associations were analysed by logistic regression. The risk of self-reported chlamydial infection decreases with age, is higher among individuals both who personally, and whose parents, were educated to high school level compared to university level education, and is higher among those employed, unemployed or on sick-leave/pre-retired compared to students. The risk of chlamydial infection is also higher among subjects who report greater alcohol consumption, and those who live without a partner. After considering demographic, socio-economic and lifestyle factors, the associations with age, educational level, employment status and alcohol consumption are strong and statistically significant. Indicators of risk-taking behaviours, especially in settings with generally little educational ambition or options, should be incorporated in the design of STI prevention strategies.

The prevalence and correlates of subclinical atherosclerosis among adults with low-density lipoprotein cholesterol ELSA-Brasil).

Science.gov (United States)

Al Rifai, Mahmoud; Martin, Seth S; McEvoy, John W; Nasir, Khurram; Blankstein, Ron; Yeboah, Joseph; Miedema, Michael; Shea, Steven J; Polak, Joseph F; Ouyang, Pamela; Blumenthal, Roger S; Bittencourt, Marcio; Bensenor, Isabela; Santos, Raul D; Duncan, Bruce B; Santos, Itamar S; Lotufo, Paulo A; Blaha, Michael J

2018-07-01

The prevalence and correlates of subclinical atherosclerosis when low-density lipoprotein cholesterol (LDL-C) levels are low remain unclear. Therefore, we examined the association of cardiovascular risk factors and subclinical atherosclerosis among individuals with untreated LDL-C ELSA-Brasil) cohorts. To optimize accuracy, LDL-C was calculated by the validated Martin/Hopkins equation that uses an adjustable factor for the ratio of triglycerides to very low-density lipoprotein cholesterol. We defined subclinical atherosclerosis as a coronary artery calcium (CAC) score >0 in the combined cohort or common carotid intima media thickness (cIMT) in the 4 th quartile, using cohort-specific cIMT distributions at baseline. Logistic regression models examined the cross-sectional associations of cardiovascular risk factors and subclinical atherosclerosis. Among 9411 participants not on lipid lowering therapy, 263 (3%) had LDL-C ELSA: 57). Mean age in this population was 58 (SD 12) years, with 43% men, and 41% Black. The prevalence of CAC >0 in those with untreated LDL-C<70 mg/dL was 30%, and 18% were in 4th quartile of cIMT. In demographically adjusted models, only ever smoking was significantly associated with both CAC and cIMT. Similar results were obtained in risk factor-adjusted models (smoking: OR, 2.29; 95% CI, 1.10-4.80 and OR, 3.44; 95% CI, 1.41-8.37 for CAC and cIMT, respectively). Among middle-aged to older individuals with untreated LDL-C <70 mg/dL, subclinical atherosclerosis remains moderately common and is associated with cigarette smoking. Copyright © 2018 Elsevier B.V. All rights reserved.

IKKε knockout prevents high fat diet induced arterial atherosclerosis and NF-κB signaling in mice.

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Changchun Cao

Full Text Available AIMS: Atherosclerosis is a public health concern affecting many worldwide, but its pathogenesis remains unclear. In this study we investigated the role of IKKε during the formation of atherosclerosis and its molecular mechanism in the mouse aortic vessel wall. METHODS AND RESULTS: C57BL/6 wild-type or IKKε knockout mice bred into the ApoE knockout genetic background were divided into 4 groups: (1 wild-type (WT, (2 ApoE knockout (AK, (3 IKKε knockout (IK, (4 or both ApoE and IKKε knockout (DK. Each group of mice were fed with a high fat diet (HFD for 12 weeks from 8 weeks of age. Immunohistochemistry and Western blotting analysis demonstrated obvious increases in the expression of IKKε in the AK group compared with the WT group, especially in the intima. Serum lipid levels were significantly higher in the AK and DK groups than in the other two groups. Staining with hematoxylin-eosin and Oil Red, as well as scanning electron microscopy revealed less severe atherosclerotic lesions in the DK group than in the AK group. Immunofluorescence and Western blot analysis demonstrated obvious increases in the expression of NF-κB pathway components and downstream factors in the AK group, especially in the intima, while these increases were blocked in the DK group. CONCLUSION: The knockout of IKKε prevented significant atherosclerosis lesions in the mouse aorta from in both wild-type and ApoE knockout mice fed a HFD, suggesting that IKKε may play a vital role in HFD-induced atherosclerosis and would be an important target for the treatment of atherosclerosis.

[Chronic mild inflammation links obesity, metabolic syndrome, atherosclerosis and diabetes].

Science.gov (United States)

Andel, M; Polák, J; Kraml, P; Dlouhý, P; Stich, V

2009-01-01

Chronic low grade inflammation is relatively new concept in metabolic medicine. This concept describes the relations between the inflammation and adipose tissue, insulin resistence, atherosclerosis and type 2 diabetes mellitus. Macrophages and lymphocytes deposed in adipose tissue produce proinflammatory cytokines which directly or through the CRP liver secretion are targeting endothelial cells, hepatocytes and beta cells of Langerhans islets of pancreas. The dysfunction of these cells follows often further disturbances and in case of beta cells - the cell death. The connection between the adipose tissue insulin resistence, atherosclerosis and type 2 diabetes was earlier described with endocrine and metabolic descriptors. The concept of chronic low grade inflammation creates also another description of multilateral connections in metabolic syndome. The salicylates and the drugs related to them seem to have some glucose lowering properties. The recent development in the field ofchronic low grade inflammation represents also certain therapeutic hope for antiinflammatory intervention in type 2 diabetes.

Pentosan polysulfate inhibits atherosclerosis in Watanabe heritable hyperlipidemic rabbits: differential modulation of metalloproteinase-2 and -9.

Science.gov (United States)

Lupia, Enrico; Zheng, Feng; Grosjean, Fabrizio; Tack, Ivan; Doublier, Sophie; Elliot, Sharon J; Vlassara, Helen; Striker, Gary E

2012-02-01

Pentosan polysulfate (PPS), a heparinoid compound essentially devoid of anticoagulant activity, modulates cell growth and decreases inflammation. We investigated the effect of PPS on the progression of established atherosclerosis in Watanabe heritable hyperlipidemic (WHHL) rabbits. After severe atherosclerosis developed on an atherogenic diet, WHHL rabbits were treated with oral PPS or tap water for 1 month. The aortic intima-to-media ratio and macrophage infiltration were reduced, plaque collagen content was increased, and plaque fibrous caps were preserved by PPS treatment. Plasma lipid levels and post-heparin hepatic lipase activity remained unchanged. However, net collagenolytic activity in aortic extracts was decreased, and the levels of matrix metalloproteinase (MMP)-2 and tissue inhibitor of metalloproteinase (TIMP) activity were increased by PPS. Moreover, PPS treatment decreased tumor necrosis factor α (TNFα)-stimulated proinflammatory responses, in particular activation of nuclear factor-κB and p38, and activation of MMPs in macrophages. In conclusion, oral PPS treatment prevents progression of established atherosclerosis in WHHL rabbits. This effect may be partially mediated by increased MMP-2 and TIMP activities in the aortic wall and reduced TNFα-stimulated inflammation and MMP activation in macrophages. Thus, PPS may be a useful agent in inhibiting the progression of atherosclerosis.

Machine Learning Methods for Knowledge Discovery in Medical Data on Atherosclerosis

Czech Academy of Sciences Publication Activity Database

Serrano, J.I.; Tomečková, Marie; Zvárová, Jana

2006-01-01

Roč. 1, - (2006), s. 6-33 ISSN 1801-5603 Institutional research plan: CEZ:AV0Z10300504 Keywords : knowledge discovery * supervised machine learning * biomedical data mining * risk factors of atherosclerosis Subject RIV: BB - Applied Statistics, Operational Research

[Estimation of relation between homocysteine concentration and selected lipid parameters and adhesion molecules concentration in children with atherosclerosis risk factors].

Science.gov (United States)

Sierakowska-Fijałek, Anna; Baj, Zbigniew; Kaczmarek, Piotr; Stepień, Mariusz; Rysz, Jacek

2008-10-01

Atherosclerosis begins in childhood. At present among numerous risk factors of atherosclerosis the role of hiperhomocysteinemia in development of cardiovascular heart disease is taken under consideration. Atherogenic effect of homocystein is related to its cytotoxin action, conducting to endothelial dysfunction and damage. It is correlated with increase of the lipid levels in the blood serum and change of expression of the soluble forms of adhesion molecules. The aim of this study was to estimate relations between the homocystein serum concentration, expression of the selected adhesion molecules and the lipid levels in the blood serum in children with atherosclerosis risk factors. The group consisted of 670 children, 76 of them had atherosclerosis risk factors. In further examination 48 children have taken a part, whose parents were agreed for theirs participation in the program. The comparative group composed of 25 children without the risk factors. We determined total cholesterol (TC), triglycerides (TG), LDL cholesterol fraction (LDL-C), HDL cholesterol fraction (HDL-C), serum homocysteine concentration (Hcy), the expression of the soluble forms of adhesion molecules (sCAM): sP-selectin and sVCAM-1 (vascular cell adhesion molecule-1). Obesity, hypertension and lipid disorders in the shape of higher concentration of TC, LDL-C, TG and lower HDL-C were the most frequent risk factors in the investigated children. No significant differences in serum homocysteine concentration were observed between the investigated groups. However, its concentration was significantly higher in children with two atherosclerosis risk factors. No significant differences in expression of s-VCAM-1 were observed in the investigated groups, concentration of sP-selectin was significantly higher in children with atherosclerosis risk factors (phomocysteine and chosen adhesion molecules in children with atherosclerosis risk factors might potentially constitute the marker of early

Serum levels of psoriasin (S100A7) and koebnerisin (S100A15) as potential markers of atherosclerosis in patients with psoriasis.

Science.gov (United States)

Awad, S M; Attallah, D A; Salama, R H; Mahran, A M; Abu El-Hamed, E

2018-04-01

Psoriasin (S100A7) and koebnerisin (S100A15) are proinflammatory proteins upregulated in psoriasis, but their relation to atherosclerosis remains unclear. To evaluate the role of serum psoriasin and koebnerisin as possible markers for subclinical atherosclerosis in patients with psoriasis. Serum levels of psoriasin and koebnerisin were measured by ELISA in 45 patients with psoriasis and in 45 healthy controls (HCs). Intima-media thickness (IMT) of the right and left common carotid arteries was measured to detect the presence of subclinical atherosclerosis. Clinical severity of psoriasis was estimated using the Psoriasis Area and Severity Index (PASI). Compared with HCs, patients with psoriasis had significantly higher levels of psoriasin (26.61 ± 22.45 ng/mL vs. 6.31 ± 1.68 ng/mL, P  0.01) and serum koebnerisin (r = 0.48, P psoriasis with subclinical atherosclerosis had higher serum levels of koebnerisin compared with patients without subclinical atherosclerosis (P = 0.04), which was not observed for psoriasin (P = 0.94). Serum psoriasin and koebnerisin correlate with IMT, underlining their value as a potential link between psoriasis and atherosclerosis. In particular, koebnerisin seems to be a useful marker of subclinical atherosclerosis in patients with psoriasis. © 2018 British Association of Dermatologists.

Urinary arsenic methylation capability and carotid atherosclerosis risk in subjects living in arsenicosis-hyperendemic areas in southwestern Taiwan

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Huang, Y.-L. [Department of Public Health, School of Medicine, Taipei Medical University, Taipei, Taiwan (China); Hsueh, Y.-M. [Department of Public Health, School of Medicine, Taipei Medical University, Taipei, Taiwan (China)], E-mail: ymhsueh@tmu.edu.tw; Huang, Y.-K. [Graduate Institute of Medical Sciences, School of Medicine, Taipei Medical University, Taipei, Taiwan (China); Yip, P.-K. [Department of Neurology, College of Medicine, National Taiwan University, Taiwan (China); Yang, M.-H. [Department of Nuclear Science, National Tsing-Hua University, Hsinchu, Taiwan (China); Chen, C.-J. [Genomics Research Center, Academia Sinica, Taipei, Taiwan (China); Graduate Institute of Epidemiology, College of Public Health, National Taiwan University Taipei, Taiwan (China)

2009-04-01

Long-term exposure to inorganic arsenic from artesian drinking well water is associated with carotid atherosclerosis in the Blackfoot Disease (BFD)-hyperendemic area in Taiwan. The current study examined the arsenic methylation capacity and its risk on carotid atherosclerosis. A total of 304 adults (158 men and 146 women) residing in the BFD-hyperendemic area were included. The extent of carotid atherosclerosis was assessed by duplex ultrasonography. Chronic arsenic exposure was estimated by an index of cumulative arsenic exposure (CAE) and the duration of artesian well water consumption. Urinary levels of inorganic arsenite [As(III)], arsenate [As(V)], monomethylarsonic acid [MMA(V)] and dimethylarsinic acid [DMA(V)] were determined by high performance liquid chromatography linked on-line to a hydride generator and atomic absorption spectrometry (HPLC-HG-AAS). The percentage of arsenic species, primary methylation index [PMI = MMA(V) / (As(III) + As(V)] and secondary methylation index [SMI = DMA(V) / MMA(V)] were calculated and employed as indicators of arsenic methylation capacity. Results showed that women and younger subjects had a more efficient arsenic methylation capacity than did men and the elderly. Carotid atherosclerosis cases had a significantly greater percentage of MMA(V) [%MMA(V)] and a lower percentage of DMA [%DMA (V)] compared to controls. Subjects in the highest two tertiles of PMI with a median of CAE > 0 mg/L-year had an odds ratio (OR) and a 95% confidence interval (CI) of carotid atherosclerosis of 2.61 and 0.98-6.90 compared to those in the highest two tertiles of PMI with a CAE = 0 mg/L-year. We conclude that individuals with greater exposure to arsenic and lower capacity to methylate inorganic arsenic may be at a higher risk to carotid atherosclerosis.

Urinary arsenic methylation capability and carotid atherosclerosis risk in subjects living in arsenicosis-hyperendemic areas in southwestern Taiwan

International Nuclear Information System (INIS)

Huang, Y.-L.; Hsueh, Y.-M.; Huang, Y.-K.; Yip, P.-K.; Yang, M.-H.; Chen, C.-J.

2009-01-01

Long-term exposure to inorganic arsenic from artesian drinking well water is associated with carotid atherosclerosis in the Blackfoot Disease (BFD)-hyperendemic area in Taiwan. The current study examined the arsenic methylation capacity and its risk on carotid atherosclerosis. A total of 304 adults (158 men and 146 women) residing in the BFD-hyperendemic area were included. The extent of carotid atherosclerosis was assessed by duplex ultrasonography. Chronic arsenic exposure was estimated by an index of cumulative arsenic exposure (CAE) and the duration of artesian well water consumption. Urinary levels of inorganic arsenite [As(III)], arsenate [As(V)], monomethylarsonic acid [MMA(V)] and dimethylarsinic acid [DMA(V)] were determined by high performance liquid chromatography linked on-line to a hydride generator and atomic absorption spectrometry (HPLC-HG-AAS). The percentage of arsenic species, primary methylation index [PMI = MMA(V) / (As(III) + As(V)] and secondary methylation index [SMI = DMA(V) / MMA(V)] were calculated and employed as indicators of arsenic methylation capacity. Results showed that women and younger subjects had a more efficient arsenic methylation capacity than did men and the elderly. Carotid atherosclerosis cases had a significantly greater percentage of MMA(V) [%MMA(V)] and a lower percentage of DMA [%DMA (V)] compared to controls. Subjects in the highest two tertiles of PMI with a median of CAE > 0 mg/L-year had an odds ratio (OR) and a 95% confidence interval (CI) of carotid atherosclerosis of 2.61 and 0.98-6.90 compared to those in the highest two tertiles of PMI with a CAE = 0 mg/L-year. We conclude that individuals with greater exposure to arsenic and lower capacity to methylate inorganic arsenic may be at a higher risk to carotid atherosclerosis