Imaging of Oxidation-Specific Epitopes in Atherosclerosis and Macrophage-Rich Vulnerable Plaques

Oxidative stress, and in particular oxidation of lipoproteins, is a hallmark of atherosclerosis. Upon entry of lipoproteins into the vessel wall, a cascade of pro-atherogenic pathways is initiated whereby the reaction of reactive oxygen species with substrates amenable to oxidation, such as polyunsaturated fatty acids, generates a variety of oxidation-specific epitopes on lipoproteins, proteins in the vessel wall, and apoptotic macrophages. Several of these oxidation-specific epitopes have been well characterized and specific murine and fully human antibodies have been generated in our laboratory to detect them in the vessel wall. We have developed radionuclide, gadolinium and iron oxide based MRI techniques to noninvasively image oxidation-specific epitopes in atherosclerotic lesions. These approaches quantitate plaque burden and also allow detection of atherosclerosis regression and plaque stabilization. In particular, gadolinium micelles or lipid-coated ultrasmall superparamagnetic iron oxide particles containing oxidation-specific antibodies accumulate within macrophages in the artery wall, suggesting they may image the most unstable plaques. Translation of these approaches to humans may allow a sensitive technique to image and monitor high-risk atherosclerotic lesions and may guide optimal therapeutic interventions

Doxycycline Stabilizes Vulnerable Plaque via Inhibiting Matrix Metalloproteinases and Attenuating Inflammation in Rabbits

Enhanced matrix metalloproteinases (MMPs) activity is implicated in the process of atherosclerotic plaque instability. We hypothesized that doxycycline, a broad MMPs inhibitor, was as effective as simvastatin in reducing the incidence of plaque disruption. Thirty rabbits underwent aortic balloon injury and were fed a high-fat diet for 20 weeks. At the end of week 8, the rabbits were divided into three groups for 12-week treatment: a doxycycline-treated group that received oral doxycycline at a dose of 10 mg/kg/d, a simvastatin-treated group that received oral simvastatin at a dose of 5 mg/kg/d, and a control group that received no treatment. At the end of week 20, pharmacological triggering was performed to induce plaque rupture. Biochemical, ultrasonographic, pathologic, immunohistochemical and mRNA expression studies were performed. The results showed that oral administration of doxycycline resulted in a significant increase in the thickness of the fibrous cap of the aortic plaque whereas there was a substantial reduction of MMPs expression, local and systemic inflammation, and aortic plaque vulnerability. The incidence of plaque rupture with either treatment (0% for both) was significantly lower than that for controls (56.0%, P<0.05). There was no significant difference between doxycycline-treated group and simvastatin-treated group in any serological, ultrasonographic, pathologic, immunohistochemical and mRNA expression measurement except for the serum lipid levels that were higher with doxycycline than with simvastatin treatment. In conclusion, doxycycline at a common antimicrobial dose stabilizes atherosclerotic lesions via inhibiting matrix metalloproteinases and attenuating inflammation in a rabbit model of vulnerable plaque. These effects were similar to a large dose of simvastatin and independent of serum lipid levels

Metabolic syndrome and carotid intima-media thickness in chronic obstructive pulmonary disease

BACKGROUND: The aim of this study is to investigate the prevalence of metabolic syndrome (MetS), carotid intima media thickness (IMT), and serum C-reactive protein (CRP) levels in patients with chronic obstructive pulmonary disease (COPD), and the possible relationships among them. METHODS: Fifty stable COPD patients and 40 healthy controls were included in the study. The participants were further divided into four groups according to their smoking status. Pulmonary function tests were performed in COPD patients. Anthropometric measurements and blood chemistry analysis, serum CRP levels and carotid intima-media thickness (IMT) measurements were performed in all the study population. RESULTS: Prevalence of metabolic syndrome was 43% in COPD patients and 30% in the control group (p = 0.173). FEV(1)% and FEV(1)/FVC were higher in COPD patients with MetS (p = 0.001 and p = 0.014, respectively) compared to those without MetS. Prevalence of MetS was significantly different among the COPD patients with different stages (p = 0.017) with the highest value in stage 2 (59%). Carotid IMT was significantly higher in COPD patients than in control group (1.07 ± 0.25 mm and 0.86 ± 0.18 mm, respectively; p < 0.001). Serum CRP levels were not different in COPD patients and controls, however they were higher in individuals with MetS compared to those without MetS regardless of COPD presence (p = 0.02). CONCLUSIONS: Early markers of atherogenesis, in terms of carotid IMT, were found to be higher in COPD patients than in healthy controls. MetS prevalence was observed to decrease as the severity of airflow obstruction increased. Therefore, screening COPD patients for these cardiovascular risk factors would be a novel approach even in absence of symptoms

Genetic variation in Fcγ receptor IIa and risk of coronary heart disease: negative results from two large independent populations

Background The role of the Fcgamma receptor IIa (FcgammaRIIa), a receptor for C-reactive protein (CRP), the classical acute phase protein, in atherosclerosis is not yet clear. We sought to investigate the association of FcgammaRIIa genotype with risk of coronary heart disease (CHD) in two large population-based samples. Methods FcgammaRIIa-R/H131 polymorphisms were determined in a population of 527 patients with a history of myocardial infarction and 527 age and gender matched controls drawn from a population-based MONICA- Augsburg survey. In the LURIC population, 2227 patients with angiographically proven CHD, defined as having at least one stenosis [greater than or equal to]50%, were compared with 1032 individuals with stenosis H genotype was not independently associated with lower risk of CHD after multivariable adjustments, neither in the MONICA population (odds ratio (OR) 1.08; 95% confidence interval (CI) 0.81 to 1.44), nor in LURIC (OR 0.96; 95% CI 0.81 to 1.14). Conclusion Our results do not confirm an independent relationship between FcgammaRIIa genotypes and risk of CHD in these populations

Biological foundation for periodontitis as a potential risk factor for atherosclerosis

Links between periodontal diseases and systemic diseases have been well documented by epidemiological studies. Recently, research has shifted to elucidating the biologic mechanism for a causal relationship. One focus of interest is atherosclerosis, the underlying event of cardiovascular diseases due to its serious health impact. However, it is still not clear whether periodontopathic pathogens are truly etiologic agents or ubiquitous bystanders. This article reviews the current understanding about the molecular biological interactions between periodontal disease and atherosclerosis and the biological plausibility of periodontitis as a potential risk factor for cardiovascular disease. Materials and methods:  The current literature regarding periodontal diseases and atherosclerosis and coronary vascular disease was searched using the Medline and PubMed databases. Results:  In vitro experiments and animal models are appropriate tools to investigate the biological interactions between periodontal disease and atherosclerosis at the cell molecular level. The concepts linking both pathologies refer to inflammatory response, immune responses, and hemostasis. In particular, Porphyromonas gingivalis appears to have unique, versatile pathogenic properties. Whether or not these findings from isolated cells or animal models are applicable in humans with genetic and environmental variations is yet to be determined. Likewise, the benefit from periodontal therapy on the development of atherosclerosis is unclear. Approaches targeting inflammatory and immune responses of periodontitis and atherosclerosis simultaneously are very intriguing. Conclusion:  An emerging concept suggests that a pathogenic burden from different sources might overcome an individual threshold culminating in clinical sequela. P. gingivalis contributes directly and indirectly to atherosclerosis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66109/1/j.1600-0765.2004.00771.x.pd

Cytokine-associated neutrophil extracellular traps and antinuclear antibodies in Plasmodium falciparum infected children under six years of age

<p>Abstract</p> <p>Background</p> <p>In <it>Plasmodium falciparum</it>-infected children, the relationships between blood cell histopathology, blood plasma components, development of immunocompetence and disease severity remain poorly understood. Blood from Nigerian children with uncomplicated malaria was analysed to gain insight into these relationships. This investigation presents evidence for circulating neutrophil extracellular traps (NETs) and antinuclear IgG antibodies (ANA). The presence of NETs and ANA to double-stranded DNA along with the cytokine profiles found suggests autoimmune mechanisms that could produce pathogenesis in children, but immunoprotection in adults.</p> <p>Methods</p> <p>Peripheral blood smear slides and blood samples obtained from 21 Nigerian children under six years of age, presenting with uncomplicated malaria before and seven days after initiation of sulphadoxine-pyrimethamine (SP) treatment were analysed. The slides were stained with Giemsa and with DAPI. Levels of the pro-inflammatory cytokines IFN-γ, IL-2, TNF, CRP, and IL-6, select anti-inflammatory cytokines TGF-β and IL-10, and ANA were determined by immunoassay.</p> <p>Results</p> <p>The children exhibited circulating NETs with adherent parasites and erythrocytes, elevated ANA levels, a Th2 dominated cytokine profile, and left-shifted leukocyte differential counts. Nonspecific ANA levels were significant in 86% of the children pretreatment and in 100% of the children seven days after SP treatment, but in only 33% of age-matched control samples collected during the season of low parasite transmission. Levels of ANA specific for dsDNA were significant in 81% of the children both pre-treatment and post treatment.</p> <p>Conclusion</p> <p>The results of this investigation suggest that NET formation and ANA to dsDNA may induce pathology in falciparum-infected children, but activate a protective mechanism against falciparum malaria in adults. The significance of in vivo circulating chromatin in NETs and dsDNA ANA as a causative factor in the hyporesponsiveness of CpG oligonucleotide-based malaria vaccines is discussed.</p

Resources of dead wood on surfaces for long-term research in the Kampinos National Park

The research covered 46 areas (each 400 sq.m) located in nine regions of the Kampinos National Park. This research is the result of field work carried out three times in years: 2007, 2012 and 2018. Dead wood measurements are one of the elements of testing on solid surfaces, which also includes vegetation, soil and stand. The average dead wood content in the Kampinos National Park over the past 11 years on long-term surfaces increased by 53% (from averages 35.59 m3/ha in 2007 to 54.37 m3/ha in 2018). Areas located in strictly protected zones showed greater abundance of dead wood in relation to the surface in active protection, and this difference is significant. On the surfaces covered by both forms of protection, during 11 years of research an increase in dead wood resources was noted, but only in areas covered by active protection it was statistically significant. In terms of the type of stand, oak stands with the average thickness of standing and lying wood in 2018 amounting to 110.70 m3/ha are the richest in dead wood, and the poorest pine stands with an average of 20.07 m3/ha. The results obtained on solid surfaces indicate a much greater richness of dead wood in the forests of the Kampinos National Park compared to the lowland state forests. However, due to the relatively small number of areas covered by the study, this work contributes to the knowledge of dead wood resources in this area and does not exhaust the need for a complete inventory

New records of Buxbaumia viridis (buxbaumiaceae, bryophyta) in the sudetes

Buxbaumia viridis is a rare, epixylous moss species with boreal range of occurrence. It prefers native, coniferous, spruce-fir forests. Historically the species was recorded several in the Sudetes, but now only two locations are known in this mountain range. In 2017 five unknown B. viridis populations were found in Góry Sowie Landscape Park in the vicinity of Bielawa, in the Bardzkie Mountains near Bardo Śląskie, and in the Sudety Wałbrzyskie Landscape Park on the eastern slope of Waligóra