Functional analysis of the C-reactive protein (CRP) gene -717A>G polymorphism associated with coronary heart disease

<p>Abstract</p> <p>Background</p> <p>Atherosclerosis underlies the major pathophysiological mechanisms of coronary heart disease (CHD), and inflammation contributes to all phases of atherosclerosis. C-reactive protein (CRP), a sensitive, but nonspecific marker of inflammation has been shown to play proatherogenic roles in the process of atherosclerosis. Our previous report showed that rs2794521 (-717A>G), located in the promoter of the CRP gene, was independently associated with CHD in Chinese subjects. In the present study, we tried to investigate the biological significance of this genetic variation <it>in vitro</it>.</p> <p>Methods</p> <p>The influence of G to A substitution at the site of rs2794521 on the transcriptional activity of the promoter of the CRP gene was assessed by luciferase reporter assay, and protein binding to the site of rs2794521 was detected by EMSA assay.</p> <p>Results</p> <p>The G to A exchange at the site of rs2794521 resulted in an increased transcriptional activity of the promoter of CRP gene, and glucocorticoid receptor (GR) protein factor bound drastically differently to the A and G alleles at the site of rs2794521.</p> <p>Conclusion</p> <p>These results provided functional evidence supporting the association of the SNP rs2794521 of the CRP gene with CHD probably through regulating the expression level of CRP by different variations of rs2794521.</p

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

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

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

Comparative study high-strenght steel welded used in construction of special vehicles

W artykule przedstawiono badania wytrzymałości na rozciąganie i badania zmęczeniowe wysokowytrzymałej stali S960QL i jej połączeń spawanych realizowane w temperaturze pokojowej. Badania trwałości zmęczeniowej przeprowadzono na serwohydraulicznej maszynie wytrzymałościowej pracującej w pętli sprzężenia zwrotnego. Badania zmęczeniowe realizowano na spawanych połączeniach czołowych i nakładkowych wykonanych ze stali S960QL. Obliczenia trwałości zmęczeniowej zostały wykonane z uwzględnieniem naprężenia nominalnego. Uzyskane wyniki obliczeniowe porównano z wynikami eksperymentu. Została zauważone znaczące obniżenie trwałości zmęczeniowej połączeń spawanych, szczególnie dla połączenia nakładkowego.In this article, monotonic tension and fatigue tests of S960QL high strength steel and its welded joints were investigated at room temperature. The tests of fatigue life were carried out on a computer-controlled Instron 8802 closed-loop servo-hydraulic test machine. Fatigue experiments were conducted using butt and lap joints of S960QL steel. Calculations of fatigue life were made using the nominal stress method. Obtained result were compared with experimental results. There was a significant reduction in fatigue life of welded joits, especially for lap connections

Eosinophilic meningitis due to Angiostrongylus cantonensis in Germany

We report a case of eosinophilic meningitis due to Angiostrongylus cantonensis in a patient who returned from Thailand. The presence of a compatible epidemiologic history and eosinophilia in cerebrospinal fluid (CSF) lead to the diagnosis, which was confirmed by detection of specific antibodies. After treatment with albendazole and corticosteroids he recovered completel