Proteomics of plaques and novel sources of potential biomarkers for atherosclerosis

Cardiovascular disease (CVD) is the leading cause of death and loss of productive life years in the world. The underlying syndrome of CVD, atherosclerosis, is a complex disease process, which involves lipid metabolism, inflammation, innate and adaptive immunity, and many other pathophysiological aspects. Furthermore, CVD is influenced by genetic as well as environmental factors. Early detection of CVD and identification of patients at risk are crucial to reduce the burden of disease and to allow personalized treatment. As established risk factors fail to accurately predict which part of the population is likely to suffer from the disease, novel biomarkers are urgently needed. Proteomics can play a significant role in identifying these biomarkers. In this review, we describe the progress made in proteome profiling of the atherosclerotic plaque and several novel sources of potential biomarkers, including circulating cells and plasma extracellular vesicles. The importance of longitudinal biobanking in biomarker discovery is highlighted and exemplified by several plaque proteins identified in the biobank study Athero-Express. Finally, we discuss the PTMs of proteins that are involved in atherosclerosis, which may become one of the foci in the ongoing quest for biomarkers through proteomics of plaque and other matrices relevant to the progression of atherosclerosis.     

Relation of arterial geometry to luminal narrowing and histologic markers for plaque vulnerability: the remodeling paradox

The agr P2 operon in Staphylococcus aureus codes for the elements of a density-sensing cassette made up of a typical two-component signalling system and its corresponding inducer. It is postulated that the autoinducer, a post-translationally modified octapeptide generated from the AgrD peptide, interacts with a receptor protein, coded by agrC, to transmit a signal via AgrA regulating expression of staphylococcal virulence genes through expression of agr RNA III. We show by analysis of PhoA fusions that AgrC is a transmembrane protein, and confirm using Western blotting that a 46 kDa protein corresponding to AgrC is present in the bacterial membrane. This protein is autophosphorylated on a histidine residue only in response to supernatants from an agr+ strain, and can also respond to the purified native octapeptide. A recombinant fusion protein where most of the N-terminal region of AgrC is replaced by the Escherichia coli maltose-binding protein is also autophosphorylated in response to stimulation by agr+ supernatants or purified octapeptide. We conclude that AgrC is the sensor molecule of a typical two-component signal system in S. aureus, and that the ligand-binding site of AgrC is probably located in the third extracellular loop of the protein.     

Intravascular ultrasound predictors of restenosis after balloon angioplasty of the femoropopliteal artery

The skepticism surrounding the potential benefits of resistance exercise training prevalent just decades ago has evolved over the years to an understanding of the integral nature muscular overload plays in the training programs for athletes. The science of training elite athletes is progressing rapidly, as insights into the physiological adaptations resulting from varying program configurations become available. Resistance training impacts several body systems, including muscular, endocrine, skeletal, metabolic, immune, neural, and respiratory. An understanding and appreciation of basic scientific principles related to resistance training is necessary in order to optimize training responses. Careful selection of the acute program variables in a workout to simulate sports-specific movements is required for optimal transfer of gains made in training to competition. Thus, whether athletes require predominantly eccentric, isometric, slow-velocity, or high-velocity strength or power in their athletic event will dictate the time commitment to each component and form the basis for designing individual workouts. Program variation over a training period is essential to maximize gains and prevent overtraining.     

Our university clinics need research--so does our specialty!]

University research has to serve as a substrate for science and technology and should raise a qualified, critical but motivated younger generation of scientists. These need a basic research which is independent and not oriented towards any short-term goals. An open and easy collaboration without any interdependence is necessary between the university and industry. All this requires greater autonomy for the universities. in German-speaking countries, many people distrust progress. However, it is not a matter of 'progress at any price' but of a careful, pertinent analysis of the benefits and risks. Parsimony in science and research is dangerous and shortsighted. To invest in research means to invest in the future.     

Physical design of the SL branching repeater

Since undersea fiber-optic cable can carry multiple transmission paths, it is now possible to conceive of a device which allows physical separation of the fiber paths and the subsequent routing of these paths to different landing points. This paper describes such a device now being designed for TAT 8. It has the capability of switching power from shore such that in the case of branch failure (such as might be caused by surface activities like fishing, etc.) the service in the other branch can be maintained. It also can have the capability of switching the incoming transoceanic signal paths to either shore-end cable so that all transoceanic capability can be maintained in the face of such failure.     

Cyclic diamides with (CH2) x segments: Phase transitions in the solid state

Summary Cyclic diamides with various CH₂ segment lengths were synthesized. Cyclo-(octamethylene sebacamide) I, x=8, was investigated as a model system by means of calorimetry, X-ray diffraction and Raman spectroscopy with special emphasis on its phase behaviour. In the low temperature phase the molecules exist as collapsed rings where the amide groups are located in the folds and the straight stems consist of nondisordered CH₂ segments. During the solid phase transition at about 84°C a strong increase of conformational disorder (4 additional gauche defects per molecule) occurs which does not change significantly during subsequent melting. It is shown that the conformation of the molecules in the high temperature phase is similar to that in the melt (liquid-like). In spite of conformational disorder the linewidth of the X-ray reflection peaks is smaller in the high temperature phase compared to that in the solution crystallized phase.     

Localized measurement of optical attenuation coefficients of atherosclerotic plaque constituents by quantitative optical coherence tomography

Optical coherence tomography (OCT) is a novel, high-resolution diagnostic tool that is capable of imaging the arterial wall and plaques. The differentiation between different types of atherosclerotic plaque is based on qualitative differences in gray levels and structural appearance. We hypothesize that a quantitative data analysis of the OCT signal allows measurement of light attenuation by the local tissue components, which can facilitate quantitative spatial discrimination between plaque constituents. High-resolution OCT images (at 800 nm) of human atherosclerotic arterial segments obtained at autopsy were histologically validated. Using a new, simple analysis algorithm, which incorporates the confocal properties of the OCT system, the light attenuation coefficients for these constituents were determined: for diffuse intimal thickening (5.5 +/- 1.2 mm(-1)) and lipid-rich regions (3.2 +/- 1.1 mm(-1)), the attenuation differed significantly from media (9.9 +/- 1.8 mm(-1)), calcifications (11.1 +/- 4.9 mm(-1) ) and thrombi (11.2 +/- 2.3 mm(-1)) (p < 0.01). These proof of principle studies show that simple quantitative analysis of the OCT signals allows spatial determination of the intrinsic optical attenuation coefficient of atherosclerotic tissue components within regions of interest. Combining morphological imaging by OCT with the observed differences in optical attenuation coefficients of the various regions may enhance discrimination between various plaque types.     

Qualitative and quantitative evaluation of heart sound reduction from lung sound recordings

Recursive least squares (RLS) adaptive noise cancellation (ANC) and wavelet transform (WT) ANC have been applied and compared for heart sound (HS) reduction from lung sounds (LS) recordings. Novel processes for quantitative and qualitative evaluation of any method for HS reduction from LS have also been proposed.     

Quantitative T 2 * assessment of acute and chronic myocardial ischemia/reperfusion injury in mice

Object

Imaging of myocardial infarct composition is essential to assess efficacy of emerging therapeutics. T ₂ ^* mapping has the potential to image myocardial hemorrhage and fibrosis by virtue of its short T ₂ ^* . We aimed to quantify T ₂ ^* in acute and chronic myocardial ischemia/reperfusion (I/R) injury in mice.

Materials and methods

I/R-injury was induced in C57BL/6 mice (n?=?9). Sham-operated mice (n?=?8) served as controls. MRI was performed at baseline, and 1, 7 and 28?days after surgery. MRI at 9.4?T consisted of Cine, T ₂ ^* mapping and late-gadolinium-enhancement (LGE). Mice (n?=?6) were histologically assessed for hemorrhage and collagen in the fibrotic scar.

Results

Baseline T ₂ ^* values were 17.1?±?2.0?ms. At day 1, LGE displayed a homogeneous infarct enhancement. T ₂ ^* in infarct (12.0?±?1.1?ms) and remote myocardium (13.9?±?0.8?ms) was lower than at baseline. On days 7 and 28, LGE was heterogeneous. T ₂ ^* in the infarct decreased to 7.9?±?0.7 and 6.4?±?0.7?ms, whereas T ₂ ^* values in the remote myocardium were 14.2?±?1.1 and 15.6?±?1.0?ms. Histology revealed deposition of iron and collagen in parallel with decreased T ₂ ^* .

Conclusion

T ₂ ^* values are dynamic during infarct development and decrease significantly during scar maturation. In the acute phase, T ₂ ^* values in infarcted myocardium differ significantly from those in the chronic phase. T ₂ ^* mapping was able to confirm the presence of a chronic infarction in cases where LGE was inconclusive. Hence, T ₂ ^* may be used to discriminate between acute and chronic infarctions.