Immunity, atherosclerosis and cardiovascular disease

Atherosclerosis, the major cause of cardiovascular disease (CVD), is a chronic inflammatory condition with immune competent cells in lesions producing mainly pro-inflammatory cytokines. Dead cells and oxidized forms of low density lipoproteins (oxLDL) are abundant. The major direct cause of CVD appears to be rupture of atherosclerotic plaques. oxLDL has proinflammatory and immune-stimulatory properties, causes cell death at higher concentrations and contains inflammatory phospholipids with phosphorylcholine (PC) as an interesting epitope. Antibodies against PC (anti-PC) may be atheroprotective, one mechanism being anti-inflammatory. Bacteria and virus have been discussed, but it has been difficult to find direct evidence, and antibiotic trials have not been successful. Heat shock proteins could be one major target for atherogenic immune reactions. More direct causes of plaque rupture include pro-inflammatory cytokines, chemokines, and lipid mediators. To prove that inflammation is a cause of atherosclerosis and CVD, clinical studies with anti-inflammatory and/or immune-modulatory treatment are needed. The potential causes of immune reactions and inflammation in atherosclerosis and how inflammation can be targeted therapeutically to provide novel treatments for CVD are reviewed

Cardiovascular co-morbidity in patients with rheumatic diseases

During recent years atherosclerosis, the major cause of cardiovascular disease (CVD), has been recognised as a chronic inflammatory condition in which rupture of atherosclerotic lesions appears to play a major role. The risk of CVD is raised in many rheumatic diseases. This risk is high in systemic lupus erythematosus - as much as a 50-times increase among middle-aged women has been reported. Studies on CVD and atherosclerosis in rheumatic disease could thus provide interesting information about CVD and atherosclerosis in addition to being an important clinical problem. A combination of traditional and nontraditional risk factors accounts for the increased risk of CVD and atherosclerosis in rheumatic disease. One interesting possibility is that atherosclerotic lesions in rheumatic disease are more prone to rupture than normal atherosclerotic lesions. It is also likely that increased risk of thrombosis may play an important role, not least in systemic lupus erythematosus. Further, it is not clear whether an increased risk of CVD is a general feature of rheumatic disease, or whether this only occurs among subgroups of patients. It should be emphasised that there is an apparent lack of treatment studies where CVD in rheumatic disease is the end point. Control of disease activity and of traditional risk factors, however, appears to be well founded in relation to CVD in rheumatic disease. Further studies are needed to determine the exact role of lipid-lowering drugs as statins. Hopefully novel therapies can be developed that target the causes of the inflammation in atherosclerotic lesions both in rheumatic patients and in the general population

Host Range and Symbiotic Effectiveness of N2O Reducing Bradyrhizobium Strains

Emissions of the potent greenhouse gas N2O is one of the environmental problems associated with intensive use of synthetic N fertilizers, and novel N2O mitigation strategies are needed to minimize fertilizer applications and N2O release without affecting agricultural efficiencies. Increased incorporation of legume crops in agricultural practices offers a sustainable alternative. Legumes, in their symbiosis with nitrogen fixing bacteria, rhizobia, reduce the need for fertilizers and also respond to the need for increased production of plant-based proteins. Not all combinations of rhizobia and legumes result in efficient nitrogen fixation, and legume crops therefore often need to be inoculated with compatible rhizobial strains. Recent research has demonstrated that some rhizobia are also very efficient N2O reducers. Several nutritionally and economically important legumes form root nodules in symbiosis with bacteria belonging to Bradyrhizobium. Here, the host-ranges of fourteen N2O reducing Bradyrhizobium strains were tested on six legume hosts; cowpea, groundnut, mung bean, haricot bean, soybean, and alfalfa. The plants were grown for 35 days in pots in sterile sand supplemented with N-free nutrient solution. Cowpea was the most promiscuous host nodulated by all test strains, followed by groundnut (11 strains) and mungbean (4 strains). Three test strains were able to nodulate all these three legumes, while none nodulated the other three hosts. For cowpea, five strains increased the shoot dry weight and ten strains the shoot nitrogen content (pairwise comparison; p < 0.05). For groundnut the corresponding results were three and nine strains. The symbiotic effectiveness for the different strains ranged from 45 to 98% in cowpea and 34 to 95% in groundnut, relative to fertilized controls. The N2O reduction capacity of detached nodules from cowpea plants inoculated with one of these strains confirmed active N2O reduction inside the nodules. When released from senescent nodules such strains are expected to also act as sinks for N2O produced by denitrifying organisms in the soil microbial community. Our strategy to search among known N2O-reducing Bradyrhizobium strains for their N2-fixation effectiveness successfully identified several strains which can potentially be used for the production of legume inoculants with the dual capacities of efficacious N2-fixation and N2O reduction

Nitrite kinetics during anoxia: the role of abiotic reactions versus microbial reduction

Anoxic spells in soil induce denitrification, i.e. the sequential reduction NO3-→NO2-→NO→N2O→N2, catalysed by the four enzymes NAR, NIR, NOR and NOS, respectively. Transient accumulation of all intermediates is inevitable, but the concentrations depend on the regulation of gene expression and the physical/chemical properties of the soil. Nitrite is chemically unstable at low pH, decomposing via a conglomerate of abiotic reactions with metals and organic compounds which can result in production of NO, N2O, N2 and nitrosated organic compounds (R-NO). There is evidence that acidic soils accumulate less nitrite than neutral soils, but it is unclear if this is due to high abiotic decomposition rate (VADEC) or fast enzymatic reduction of nitrite (VNIR) at low pH. To investigate this, we monitored the kinetics of NO2-, NO, N2O and N2 during anoxic incubations of three organic soils with pHCaCl2 ranging from 3.4 to 7.2, taken from a long-term liming experiment. In parallel, we determined the rate of abiotic nitrite decay (VADEC) and its product stoichiometry (NO, N2O and R-NO) in gamma-irradiated soils. VADEC was clearly first-order with respect to HNO2 (kHNO2 = 1.4 h-1), N-gas production (NO, N2O and N2) accounted for only ~50% of VADEC, the rest was ascribed to nitrosation (R-NO). During denitrification (live soil incubation), the nitrite concentrations reached 2-3 mM in the soils with pH 4.9 and 7.2, while the soil with pH 3.4 kept nitrite concentrations at 20-50 µM , except for a short spike reaching 160 μM. Estimated rates of nitrite scavenging by the two competing sinks (NIR and ADEC) showed that NIR was the strongst nitrite sink in soil with pH 3.4 (VNIR>VADEC), while VNIR ≈ VADEC in the soil with pH 5.9. In the soil with pH 7.2, VADEC was insignificant. Thus, the regulation of denitrification (high VNIR relative to VNAR) played a crucial role in determining nitrite kinetics, hence the fate of nitrite in acid soils. High nitrite reductase activity effectively minimized abiotic nitrite decomposition and nitrosation of soil organic matter. The results shed light on regulation of denitrification in acid soils, and its implications for the fate of nitrogen during denitrification events.Nitrite kinetics during anoxia: the role of abiotic reactions versus microbial reductionacceptedVersio

In Situ Bioremediation through Mulching of Soil Polluted by a Copper–Nickel Smelter

Received for publication September 8, 2000. Bioremediation of a heavy metal–polluted soil was investigated in a 3-yr field experiment by adding mulch to a polluted forest floor. The mulch consisted of a mixture of compost and woodchips. The remediation treatment decreased the toxicity of the soil solution to bacteria as determined by the [3H]-thymidine incorporation technique, that is, by measuring the growth rate of soil bacteria extracted from unpolluted humus after exposing them to soil solution containing heavy metals from the experimental plots. Canonical correlation analysis was performed in order to identify the chemical and microbiological changes in the soil. The pH of the mulched organic layer increased by one unit. The concentration of complexed Cu increased and that of free Cu2+ decreased in the soil solution from the mulch treatment. According to basal respiration and litter decomposition, microbial activity increased during the 3 yr following the remediation treatment. The [3H]-thymidine incorporation technique was also used to study the growth rate and tolerance of bacteria to Cu. The bacterial growth rate increased and the Cu tolerance decreased on the treated plots. The structure of the microbial community, as determined by phospholipid fatty acid (PLFA) analysis, remained unchanged. The results indicate that remediation of the polluted soil had occurred, and that adding a mulch to the forest floor is a suitable method for remediating heavy metal–polluted soil

Presence of Actinobacterial and Fungal Communities in Clean and Petroleum Hydrocarbon Contaminated Subsurface Soil

Relatively little is known about the microbial communities adapted to soil environments contaminated with aged complex hydrocarbon mixtures, especially in the subsurface soil layers. In this work we studied the microbial communities in two different soil profiles down to the depth of 7 m which originated from a 30-year-old site contaminated with petroleum hydrocarbons (PHCs) and from a clean site next to the contaminated site. The concentration of oxygen in the contaminated soil profile was strongly reduced in soil layers below 1 m depth but not in the clean soil profile. Total microbial biomass and community composition was analyzed by phospholipid fatty acid (PLFA) measurements. The diversity of fungi and actinobacteria was investigated more in detail by construction of rDNA-based clone libraries. The results revealed that there was a significant and diverse microbial community in subsoils at depth below 2 m, also in conditions where oxygen was limiting. The diversity of actinobacteria was different in the two soil profiles; the contaminated soil profile was dominated by Mycobacterium -related sequences whereas sequences from the clean soil samples were related to other, generally uncultured organisms, some of which may represent two new subclasses of actinobacteria. One dominating fungal sequence which matched with the ascomycotes Acremonium sp. and Paecilomyces sp. was identified both in clean and in contaminated soil profiles. Thus, although the relative amounts of fungi and actinobacteria in these microbial communities were highest in the upper soil layers, many representatives from these groups were found in hydrocarbon contaminated subsoils even under oxygen limited conditions

Atheroprotective natural anti-phosphorylcholine antibodies of IgM subclass are decreased in Swedish controls as compared to non-westernized individuals from New Guinea

OBJECTIVE: To determine the importance of IgM antibodies against phosphorylcholine (aPC), a novel protective factor for cardiovascular disease (CVD), in a population with a non-western life style as compared with a Swedish control group. METHODS AND RESULTS: Risk factors for cardiovascular disease were determined in a group of 108 individuals aged 40–86 years from New Guinea and 108 age-and sex-matched individuals from a population based study in Sweden. Antibodies were tested by ELISA. aPC IgM levels were significantly higher among New Guineans than among Swedish controls (p < 0.0001). This difference remained significant among both men and women when controlled for LDL and blood pressure which were lower and smoking which was more prevalent in New Guineans as compared to Swedish controls (p < 0.0001). aPC IgM was significantly and negatively associated with age and systolic blood pressure among Swedish controls and with waist circumference among New Guineans. aPC IgM levels were significantly higher among women than men in both groups. The proportion of the saturated fatty acid (FA) myristic acid in serum cholesterol esters was negatively but polyunsaturated eicosapentaenoic acid and also lipoprotein (a) were positively associated with aPC IgM levels. CONCLUSION: IgM-antibodies against PC, which have atheroprotective properties, are higher in a population from Kitava, New Guinea with a traditional lifestyle, than in Swedish Controls, and higher among women than men in both populations tested. Such antibodies could contribute to the low incidence of cardiovascular disease reported from Kitava and could also provide an explanation as to why women have a later onset of CVD than men

Denitrification by bradyrhizobia under feast and famine and the role of the bc1 complex in securing electrons for N2O reduction.

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