Stress-induced differential gene expression in cardiac tissue.

The stress response is adaptive and aims to guarantee survival. However, the persistence of a stressor can culminate in pathology. Catecholamines released as part of the stress response over activate beta adrenoceptors (ß-AR) in the heart. Whether and how stress affects the expression of components of the intracellular environment in the heart is still, however, unknown. This paper used microarray to analyze the gene expression in the left ventricle wall of rats submitted to foot shock stress, treated or not treated with the selective ß2-AR antagonist ICI118,551 (ICI), compared to those of non-stressed rats also treated or not with ICI, respectively. The main findings were that stress induces changes in gene expression in the heart and that ß2-AR plays a role in this process. The vast majority of genes disregulated by stress were exclusive for only one of the comparisons, indicating that, in the same stressful situation, the profile of gene expression in the heart is substantially different when the ß2-AR is active or when it is blocked. Stress induced alterations in the expression of such a large number of genes seems to be part of stress-induced adaptive mechanism.

Resilient three-dimensional ordered architectures assembled from nanoparticles by DNA.

Rapid developments of DNA-based assembly methods provide versatile capabilities in organizing nanoparticles (NPs) in three-dimensional (3D) organized nanomaterials, which is important for optics, catalysis, mechanics, and beyond. However, the use of these nanomaterials is often limited by the narrow range of conditions in which DNA lattices are stable. We demonstrate here an approach to creating an inorganic, silica-based replica of 3D periodic DNA-NP structures with different lattice symmetries. The created ordered nanomaterials, through the precise 3D mineralization, maintain the spatial topology of connections between NPs by DNA struts and exhibit a controllable degree of the porosity. The formed silicated DNA-NP lattices exhibit excellent resiliency. They are stable when exposed to extreme temperatures (>1000°C), pressures (8 GPa), and harsh radiation conditions and can be processed by the conventional nanolithography methods. The presented approach allows the use of a DNA assembly strategy to create organized nanomaterials for a broad range of operational conditions.

Controlling the Formation and Structure of Nanoparticle Superlattices through Surface Ligand Behavior.

The tailoring of nanoparticle superlattices is fundamental to the design of novel nanostructured materials and devices. To obtain specific collective properties of these nanoparticle superlattices, reliable protocols for their self-assembly are required. This study provides insight into the self-assembly process by using oleate-covered CeO2 nanoparticles (cubic and polyhedral shapes) through the correlation of experimental and theoretical investigations. The self-assembly of CeO2 nanoparticles is controlled by tuning the colloid deposition parameters (temperature and evaporation rate), and the ordered structures so obtained were correlated to the Gibbs free energy variation of the system. The analysis of the interparticle force contributions for each structure showed the importance of both the effective ligand mean size and its Flory-Huggins parameter in determining the total potential energies. Additionally, the roles of ligand solubility and effective mean size were used to understand the formation of specific superlattice phases as a function of temperature and ligand accommodation in the arrangement. Furthermore, the face-to-face interactions between nanoparticles were correlated to the type of exposed crystallographic facet in each particle.

Lack of Association Between ACE Indel Polymorphism and Cardiorespiratory Fitness in Physically Active and Sedentary Young Women.

BACKGROUND: Polymorphisms at the angiotensin-converting enzyme gene (ACE), such as the indel [rs1799752] variant in intron 16, have been shown to be associated with aerobic performance of athletes and non-athletes. However, the relationship between ACE indel polymorphism and cardiorespiratory fitness has not been always demonstrated. OBJECTIVES: The relationship between ACE indel polymorphism and cardiorespiratory fitness was investigated in a sample of young Caucasian Brazilian women. PATIENTS AND METHODS: This study investigated 117 healthy women (aged 18 to 30 years) who were grouped as physically active (n = 59) or sedentary (n = 58). All subjects performed an incremental exercise test (ramp protocol) on a cycle-ergometer with 20-25 W/min increments. Blood samples were obtained for DNA extraction and to analyze metabolic and hormonal profiles. ACE indel polymorphism was determined by polymerase chain reaction (PCR) and fragment size analysis. RESULTS: The physically active group had higher values of peak oxygen uptake (VO2 peak), carbon dioxide output (VCO2), ventilation (VE) and power output than the sedentary group (P < 0.05) at the peak of the exercise test. However, heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) did not differ between groups. There was no relationship between ACE indel polymorphism and cardiorespiratory variables during the test in both the physically active and sedentary groups, even when the dominant (DD vs. D1 + 2) and recessive (2 vs. DI + DD) models of inheritance were tested. CONCLUSIONS: These results do not support the concept that the genetic variation at the ACE locus contributes to the cardiorespiratory responses at the peak of exercise test in physically active or sedentary healthy women. This indicates that other factors might mediate these responses, including the physical training level of the women.

Anisotropic nanocrystal dissolution observation by in situ transmission electron microscopy.

In this study, some keys in the knowledge of nanocrystals dissolving by the direct phenomenon observations are provided through in situ transmission electron microscopy experiments. The new characteristic of anisotropic nanoparticles dissolving is discussed and correlated with the evolution of the crystal to reach a minimum surface free energy (Gibbs-Wulff theorem), which has an impact on the nanocrystal ripening models. The process whereby the ripening occurs was identified and correlated to the adparticle motion.

The influence of left ventricular size and global function on regional myocardial contraction and relaxation in an adult population free of cardiovascular disease: a tagged CMR study of the MESA cohort.

The purpose of this study is to evaluate the relationship between LV structure and function with regional myocardial function in participants of the Multi-Ethnic Study of Atherosclerosis, which is a prospective study including 4 ethnic groups free from clinical cardiovascular disease. Peak systolic strain (Ecc) and regional strain rates (SRS and SRE) were calculated by harmonic phase from tagged CMR of 1100 participants. The relationships of ejection fraction (EF), end-systolic volume (ESV) and end-diastolic volume (EDV) with Ecc and strain rate were studied before and after adjustment for cardiovascular risk factors. Direct linear relationships between EF and regional systolic and diastolic functions (Ecc, SRS and SRE) were present in almost all of the regions (p < 0.05, i.e., greater EF, greater Ecc, SRS and SRE). LVESV demonstrated a negative relationship with Ecc and SRS (i.e., greater ESV, lower systolic function, indexed by Ecc and SRS) in all regions (p < or = 0.05). LVEDV was inversely related to systolic function, indexed by SR(S) (p < 0.05) in all regions. In conclusion, LVEF is directly related to systolic myocardial function, indexed as the absolute magnitude of systolic strain and strain rate. In addition, left ventricular size, indexed as end-diastolic and end-systolic volumes are inversely related to absolute systolic myocardial strain rate (SRS). These results are crucial to the interpretation of strain alterations induced by left ventricular remodeling in early heart failure.

Multidetector computed tomography myocardial perfusion imaging during adenosine stress.

OBJECTIVES: The purpose of this study is to validate the accuracy of multidetector computed tomography (MDCT) to measure differences in regional myocardial perfusion during adenosine stress in a canine model of left anterior descending (LAD) artery stenosis, during first-pass, contrast-enhanced helical MDCT. BACKGROUND: Myocardial perfusion imaging by MDCT may have significant implications in the diagnosis and treatment of coronary artery disease. METHODS: Eight dogs were prepared with a LAD stenosis, and contrast-enhanced MDCT imaging was performed 5 min into adenosine infusion (0.14 to 0.21 mg/kg/min). Images were analyzed using a semiautomated approach to define the regional signal density (SD) ratio (myocardial SD/left ventricular blood pool SD) in stenosed and remote territories, and then compared with microsphere myocardial blood flow (MBF) measurements. RESULTS: Mean MBF in stenosed versus remote territories was 1.37 +/- 0.46 ml/g/min and 1.29 +/- 0.48 ml/g/min at baseline (p = NS) and 2.54 +/- 0.93 ml/g/min and 8.94 +/- 5.74 ml/g/min during adenosine infusion, respectively (p < 0.05). Myocardial SD was 92.3 +/- 39.5 HU in stenosed versus 180.4 +/- 41.9 HU in remote territories (p < 0.001). There was a significant linear association of the SD ratio with MBF in the stenosed territory (R = 0.98, p = 0.001) and between regional myocardial SD ratio and MBF <8 ml/g/min, slope = 0.035, SE = 0.007, p < 0.0001. Overall, there was a significant non-linear relationship over the range of flows studied (LR chi-square [2 degrees of freedom] = 31.8, p < 0.0001). CONCLUSIONS: Adenosine-augmented MDCT myocardial perfusion imaging provides semiquantitative measurements of myocardial perfusion during first-pass MDCT imaging in a canine model of LAD stenosis.

Atherosclerotic plaque characterization by multidetector row computed tomography angiography.

Multidetector row computed tomography angiography (MDCTA) is seen as a potential alternative to current imaging methods for the assessment of vessel anatomy and atherosclerotic plaque composition/morphology in a great variety of arterial beds. Recent advances represented by the increase in gantry speed to <500 ms per rotation and in the number of detector rows from 4 to 64, in addition to the decrease in slice thickness to submillimetric levels, brought significant improvement in diagnostic accuracy by coronary MDCTA. In general, it has a good correlation with both intravascular ultrasound (IVUS) and histopathology for discrimination between soft, intermediate, and calcified plaques. Plaque area and volume tend to be underestimated by 12-detector row MDCTA and overestimated by 16-detector row MDCTA, but the number of patients studied so far is relatively small. However, it seems that 64-detector row MDCTA can measure plaque area and volume with greater accuracy. Plaque remodeling is overestimated in small vessels by 12-detector row MDCTA, whereas 16- and 64-detector row MDCTA show a good correlation with IVUS. Although still under development, the potential of MDCTA to characterize atherosclerotic plaque composition as well as to precisely determine plaque area, volume, and remodeling in the future is quite promising.

CT angiography in highly calcified arteries: 2D manual vs. modified automated 3D approach to identify coronary stenoses.

BACKGROUND: Two-dimensional axial and manually-oriented reformatted images are traditionally used to analyze coronary data provided by multidetector-row computed tomography angiography (MDCTA). While apparently more accurate in evaluating calcified vessels, 2D methods are time-consuming compared with automated 3D approaches. The purpose of this study was to evaluate the performance of a modified automated 3D approach (using manual vessel isolation and different window and level settings) in a population with high calcium scores who underwent coronary half-millimeter 16-detector-row CT angiography (16 x 0.5-MDCTA). METHODS: ECG-gated 16 x 0.5-MDCTA (16 x 0.5 mm cross-sections, 0.35 x 0.35 x 0.35 mm3 isotropic voxels, 400 ms rotation) was performed after injection of iopamidol (120-ml, 300 mg/ml) in 19 consecutive patients (11 male, 62+/-10 years-old). Native arteries were independently evaluated for >or=50%-stenoses using both manual 2D and modified automated 3D approaches. Stents and bypass grafts were excluded. Conventional coronary angiography was visually analyzed by 2 observers. RESULTS: Median Agatston calcium score was 434. Sensitivities, specificities, positive and negative predictive values for detection of >or=50% coronary stenoses using the 2D and modified 3D approaches were, respectively: 74%/63%, 76%/80%, 45%/34%, and 91%/93% (p=NS for all comparisons). Overall diagnostic accuracies were 75 and 78%, respectively (p=NS). Uninterpretable vessels were, respectively: 37% (77/209) and 35% (73/209) - p=NS. Time to analyze a single study was 160+/-23 and 53+/-11 min, respectively (p<0.01). CONCLUSIONS: This modified automated 3D approach is equivalent to and significantly less time consuming than the traditional manual 2D method for evaluation of >or=50%-stenoses by 16 x 0.5-MDCTA in native coronary arteries of patients with high calcium scores.

Contrast-enhanced multidetector computed tomography viability imaging after myocardial infarction: characterization of myocyte death, microvascular obstruction, and chronic scar.

BACKGROUND: The ability to distinguish dysfunctional but viable myocardium from nonviable tissue has important prognostic implications after myocardial infarction. The purpose of this study was to validate the accuracy of contrast-enhanced multidetector computed tomography (MDCT) for quantifying myocardial necrosis, microvascular obstruction, and chronic scar after occlusion/reperfusion myocardial infarction. METHODS AND RESULTS: Ten dogs and 7 pigs underwent balloon occlusion of the left anterior descending coronary artery (LAD) followed by reperfusion. Contrast-enhanced (Visipaque, 150 mL, 325 mg/mL) MDCT (0.5 mm x 32 slice) was performed before occlusion and 90 minutes (canine) or 8 weeks (porcine) after reperfusion. MDCT images were analyzed to define infarct size/extent and microvascular obstruction and compared with postmortem myocardial staining (triphenyltetrazolium chloride) and microsphere blood flow measurements. Acute and chronic infarcts by MDCT were characterized by hyperenhancement, whereas regions of microvascular obstruction were characterized by hypoenhancement. MDCT infarct volume compared well with triphenyltetrazolium chloride staining (acute infarcts 21.1+/-7.2% versus 20.4+/-7.4%, mean difference 0.7%; chronic infarcts 4.15+/-1.93% versus 4.92+/-2.06%, mean difference -0.76%) and accurately reflected morphology and the transmural extent of injury in all animals. Peak hyperenhancement of infarcted regions occurred approximately 5 minutes after contrast injection. MDCT-derived regions of microvascular obstruction were also identified accurately in acute studies and correlated with reduced flow regions as measured by microsphere blood flow. CONCLUSIONS: The spatial extent of acute and healed myocardial infarction can be determined and quantified accurately with contrast-enhanced MDCT. This feature, combined with existing high-resolution MDCT coronary angiography, may have important implications for the comprehensive assessment of cardiovascular disease.