279 research outputs found
Low levels of IgM antibodies to oxidized cardiolipin increase and high levels decrease risk of cardiovascular disease among 60-year olds: a prospective study
Low level of physical activity in women with rheumatoid arthritis is associated with cardiovascular risk factors but not with body fat mass - a cross sectional study
<p>Abstract</p> <p>Background</p> <p>As many patients with rheumatoid arthritis (RA) have increased fat mass (FM) and increased frequency of cardiovascular diseases we evaluated if total physical activity (MET-hours) had impact on body composition and cardiovascular risk factors in women with RA.</p> <p>Methods</p> <p>Sixty-one out-ward RA women, 60.8 (57.3-64.4) years, answered a self-administered questionnaire, to estimate total daily physical activity during the previous year. Physical activity level was given as metabolic equivalents (MET) × h/day. Diet content was assessed by a food frequency questionnaire and body composition by whole-body dual-energy X-ray absorptiometry. Blood lipids and antibodies against phosphorylcholine (anti-PC) were determined.</p> <p>Results</p> <p>Forty-one percent of the women had BMI > 25, 6% were centrally obese and 80% had FM% > 30%. The median (IQR) total physical activity was 40.0 (37.4-47.7), i.e. the same activity level as healthy Swedish women in the same age. Total physical activity did not significantly correlate with disease activity, BMI or FM%. Disease activity, BMI and FM% did not differ between those in the lowest quartile of total physical activity and those in the highest quartile. However, the women in the lowest quartile of physical activity had lower HDL (p = 0.05), Apo A1 (p = 0.005) and atheroprotective natural anti-PC (p = 0.016) and higher levels of insulin (p = 0.05) and higher frequency of insulin resistance than those in the highest quartile. Women in the lowest quartile consumed larger quantities of saturated fatty acids than those in the highest quartile (p = 0.042), which was associated with high oxidized low-density lipoprotein (oxLDL).</p> <p>Conclusion</p> <p>This cross sectional study demonstrated that RA women with fairly low disease activity, good functional capacity, high FM and high frequency of central obesity had the same total physical activity level as healthy Swedish women in the same age. The amount of total physical activity was not associated with functional capacity or body composition. However, low total physical activity was associated with dyslipidemia, insulin resistance, low levels of atheroprotective anti-PC and consumption of saturated fatty acids, which is of interest in the context of increased frequency of cardiovascular disease in RA.</p
Functional polymorphism of the NFKB1 gene promoter is related to the risk of dilated cardiomyopathy
<p>Abstract</p> <p>Background</p> <p>Previous studies in experimental and human heart failure showed that nuclear factor kappa B (NF-κB) is chronically activated in cardiac myocytes, suggesting an important involvement of NF-κB in the cardiac remodeling process. A common insertion/deletion (-94 insertion/deletion ATTG, rs28362491) located between two putative key promoter regulatory elements in the <it>NFKB1 </it>gene was identified which seems to be the first potential functional <it>NFKB1 </it>genetic variation. The main goal of the present investigation was to investigate the <it>NFKB1 </it>-94 insertion/deletion ATTG polymorphism in relation to risk of dilated cardiomyopathy (DCM).</p> <p>Methods</p> <p>A total of 177 DCM patients and 203 control subjects were successfully investigated. The <it>NFKB1 </it>-94 insertion/deletion ATTG polymorphism was genotyped by using PCR-PAGE.</p> <p>Results</p> <p>Genotype frequency of <it>NFKB1 </it>-94 insertion/deletion ATTG polymorphism in DCM patients was significantly different from that in control subjects (<it>P </it>= 0.015) and the ATTG<sub>2 </sub>carrier (ATTG<sub>1</sub>/ATTG<sub>2 </sub>+ ATTG<sub>2</sub>/ATTG<sub>2</sub>) was susceptible to DCM.</p> <p>Conclusion</p> <p>Our data suggested that <it>NFKB1 </it>-94 insertion/deletion ATTG polymorphism is associated with DCM.</p
Identification of IgG1 isotype phosphorylcholine antibodies for the treatment of inflammatory cardiovascular diseases
Background Phosphorylcholine (PC) is an important pro-inflammatory damage-associated molecular pattern. Previous data have shown that natural IgM anti-PC protects against cardiovascular disease. We aimed to develop a monoclonal PC IgG antibody with anti-inflammatory and anti-atherosclerotic properties.Methods Using various techniques PC antibodies were validated and optimized. In vivo testing was performed in a femoral artery cuff model in ApoE3*Leiden mice. Safety studies are performed in rats and cynomolgus monkeys.Results A chimeric anti-PC (PC-mAb(T15), consisting of a human IgG1 Fc and a mouse T15/E06 Fab) was produced, and this was shown to bind specifically to epitopes in human atherosclerotic tissues. The cuff model results in rapid induction of inflammatory genes and altered expression of genes associated with ER stress and choline metabolism in the lesions. Treatment with PC-mAb(T15) reduced accelerated atherosclerosis via reduced expression of endoplasmic reticulum stress markers and CCL2 production. Recombinant anti-PC Fab fragments were identified by phage display and cloned into fully human IgG1 backbones creating a human monoclonal IgG1 anti-PC (PC-mAbs) that specifically bind PC, apoptotic cells and oxLDL. Based on preventing macrophage oxLDL uptake and CCL2 production, four monoclonal PC-mAbs were selected, which to various extent reduced vascular inflammation and lesion development. Additional optimization and validation of two PC-mAb antibodies resulted in selection of PC-mAb X19-A05, which inhibited accelerated atherosclerosis. Clinical grade production of this antibody (ATH3G10) significantly attenuated vascular inflammation and accelerated atherosclerosis and was tolerated in safety studies in rats and cynomolgus monkeys.Conclusions Chimeric anti-PCs can prevent accelerated atherosclerosis by inhibiting vascular inflammation directly and through reduced macrophage oxLDL uptake resulting in decreased lesions. PC-mAb represents a novel strategy for cardiovascular disease prevention.Cardiolog
Can chemical and molecular biomarkers help discriminate between industrial, rural and urban environments?
Abstract Air samples from four contrasting outdoor environments including a park, an arable farm, a waste water treatment plant and a composting facility were analysed during the summer and winter months. The aim of the research was to study the feasibility of differentiating microbial communities from urban, rural and industrial areas between seasons with chemical and molecular markers such as microbial volatile organic compounds (MVOCs) and phospholipid fatty acids (PLFAs). Air samples (3 l) were collected every 2 h for a total of 6 h in order to assess the temporal variations of MVOCs and PLFAs along the day. MVOCs and VOCs concentrations varied over the day, especially in the composting facility which was the site where more human activities were carried out. At this site, total VOC concentration varied between 80 and 170 μg m−3 in summer and 20–250 μg m−3 in winter. The composition of MVOCs varied between sites due to the different biological substrates including crops, waste water, green waste or grass. MVOCs composition also differed between seasons as in summer they are more likely to get modified by oxidation processes in the atmosphere and in winter by reduction processes. The composition of microbial communities identified by the analysis of PLFAs also varied among the different locations and between seasons. The location with higher concentrations of PLFAs in summer was the farm (7297 ng m−3) and in winter the park (11,724 ng m−3). A specific set of MVOCs and PLFAs that most represent each one of the locations was identified by principal component analyses (PCA) and canonical analyses. Further to this, concentrations of both total VOCs and PLFAs were at least three times higher in winter than in summer. The difference in concentrations between summer and winter suggest that seasonal variations should be considered when assessing the risk of exposure to these compounds
s1a 5 molecular stratification of autoimmune diseases based on epigenetic profiles
Systemic autoimmune diseases (SADs) are a group of chronic inflammatory conditions with autoimmune aetiology and many common clinical features, leading to a difficult diagnosis or deciding the appropriate treatment. Finding new treatments or applying the existing ones in a more effective way is especially hard in SADs due to the heterogeneity of molecular mechanisms within the same disease class. Based on this premise, the first step towards establishing a precision medicine strategy for SADs is to reclassify these conditions at the molecular level, which might result in a more homogenous stratification in terms of pathological molecular pathways. It is well known that the interplay of DNA methylation patterns and environmental factors, and between these, is determinant in the regulation of the immune system. This, along with the fact that the genetic contribution to disease is dependent on regulatory variants with very small effects, and the low concordance for autoimmunity in monozygotic twins suggests that epigenetic regulation may play an important role in the development of these diseases. Thus, DNA methylation information might be a valuable marker to reclassify the autoimmune disorders molecularly. We performed an unsupervised clustering analysis of genome-wide DNA methylation profiling of 437 cases distributed across 7 different clinical entities (rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, primary Sjogren´s syndrome, primary antiphospholipid antibody syndrome, mixed connective tissue disease and undifferentiated connective tissue disease) and 115 healthy individuals. In this analysis we were able to identify new groups of patients composed of the different clinical diagnoses but with common biological features
Vertical Distribution of a Soil Microbial Community as Affected by Plant Ecophysiological Adaptation in a Desert System
Autoantibodies against oxidized low-density lipoprotein and lipid profile in patients with chronic periaortitis: case–control study
Defects in Regulation of Local Immune Responses Resulting in Atherosclerosis
Atherosclerosis is nowadays generally accepted as an inflammatory disease
but the mechanism of its origin and development have not yet been fully clarified.
The present review focuses on the role of the local immune system as one of the
key players in the pathogenesis of the complex process. Its part represented by
vascular-associated lymphoid tissue (VALT) within the arterial wall participates
directly in the vascular wall's homeostatis. Its inordinate activation during
ontogenic development of an individual, this formerly defensive and physiologic
mechanism transform into a pathological process resulting in an impairing
inflammation. Hsp60, CRP and oxidized or otherwise modified LDL are serious
candidates for triggering these pathological changes. The principal role is played
by anti-Hsp60 antibodies and by shear stress originating on the surface of
endothelium due to blood flow. The experimental and clinical data
supporting this immunological hypothesis of atherosclerosis are discussed
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