Continuous exposure to low amplitude extremely low frequency electrical fields characterizing the vascular streaming potential alters elastin accumulation in vascular smooth muscle cells.

In normal development and pathology, the vascular system depends on complex interactions between cellular elements, biochemical molecules, and physical forces. The electrokinetic vascular streaming potential (EVSP) is an endogenous extremely low frequency (ELF) electrical field resulting from blood flowing past the vessel wall. While generally unrecognized, it is a ubiquitous electrical biophysical force to which the vascular tree is exposed.

Electric fields caused by blood flow modulate vascular endothelial electrophysiology and nitric oxide production.

Endothelial cells are exposed to a ubiquitous, yet unexamined electrical force caused by blood flow: the electrokinetic vascular streaming potential (EVSP). In this study, the hypothesis that extremely low frequency (ELF) electric fields parameterized by the EVSP have significant biological effects on endothelial cell properties was studied by measuring membrane potential and nitric oxide production under ELF stimulation between 0 and 2 Hz and 0-6.67 V/m.

Magnetization transfer magnetic resonance of human atherosclerotic plaques ex vivo detects areas of high protein density.

Background: Proteins are major plaque components, and their degradation is related to the plaque instability. We sought to assess the feasibility of magnetization transfer (MT) magnetic resonance (MR) for identifying fibrin and collagen in carotid atherosclerotic plaques ex vivo.

Methods: Human carotid artery specimens (n = 34) were obtained after resection from patients undergoing endarterectomy.

Study of the miscibility of cholesteryl oleate in a matrix of ceramide, cholesterol and fatty acid.

Cholesteryl esters (CE) are not generally abundant but are ubiquitous in living organisms and have markedly different properties from cholesterol because of their acyl chain. The miscibility/immiscibility of CE with biological lipid structures is a key property for their functions. In this work we study the solubility of cholesteryl oleate (ChO) in a model of the stratum corneum lipid matrix composed of ceramide C16, cholesterol and palmitic acid in excess water.

In vivo detection of vulnerable atherosclerotic plaque by MRI in a rabbit model.

Background: The ability to identify atherosclerotic plaques with a high risk for sudden disruption before stroke or myocardial infarction would be of great utility. We used a rabbit model of controlled atherothrombosis to test whether in vivo MRI can noninvasively distinguish between plaques that disrupt after pharmacological triggering (vulnerable) and those that do not (stable).

Methods And Results: Atherosclerosis was induced in male New Zealand White (n=17) rabbits by cholesterol diet and endothelial denudation of the abdominal aorta.

NMR structure of pardaxin, a pore-forming antimicrobial peptide, in lipopolysaccharide micelles: mechanism of outer membrane permeabilization.

Lipopolysaccharide (LPS), the major constituent of the outer membrane of Gram-negative bacteria, is an important element against permeability of bactericidal agents, including antimicrobial peptides. However, structural determinants of antimicrobial peptides for LPS recognition are not clearly understood. Pardaxins (Pa1, Pa2, Pa3, and Pa4) are a group of pore-forming bactericidal peptides found in the mucous glands of sole fishes.

The relationship of ectopic lipid accumulation to cardiac and vascular function in obesity and metabolic syndrome.

Storage of lipid in ectopic depots outside of abdominal visceral and subcutaneous stores, including within the pericardium and liver, has been associated with obesity, insulin resistance, and cardiovascular risk. We sought to determine whether anatomically distinct ectopic depots were physiologically correlated and site-specific effects upon cardiovascular function could be identified. Obese subjects (n = 28) with metabolic syndrome but without known atherosclerotic disease and healthy controls (n = 18) underwent magnetic resonance imaging (MRI) and proton MR spectroscopy (MRS) to quantify pericardial and periaortic lipid volumes, cardiac function, aortic compliance, and intrahepatic lipid content.

A robust rabbit model of human atherosclerosis and atherothrombosis.

Disruption and thrombosis of atherosclerotic plaques cause most acute cardiovascular events, but their systematic study has been hampered by the lack of suitable animal models. To assess the value of a modified rabbit model of atherothrombosis, we performed detailed histology of rabbit aortic plaques. Atherosclerosis was induced with a high cholesterol diet fed 2 weeks prior to and 6 weeks after balloon injury of the aorta, followed by 4 weeks of normal diet.

Magnetic resonance microscopy of flows and compressions of the circulatory, respiratory, and digestive systems in pupae of the tobacco hornworm, Manduca sexta.

Circulatory, respiratory, and digestive motions in Manduca sexta pupae were observed using proton-density weighted and fast-imaging with steady-state free procession magnetic resonance microscopy. Proton-density weighted images clearly differentiated pupal air sacs from the hemolymph and organs because, as expected, the air sacs appeared dark in these images. Steady-state free procession imaging allowed real-time monitoring of respiration and circulation, creating movies of hemolymph circulation.

Diffusion properties of NAA in human corpus callosum as studied with diffusion tensor spectroscopy.

In diffusion tensor imaging (DTI) the anisotropic movement of water is exploited to characterize microstructure. One confounding issue of DTI is the presence of intra- and extracellular components contributing to the measured diffusivity. This causes an ambiguity in determining the underlying cause of diffusion properties, particularly the fractional anisotropy (FA).

Diffusion tensor spectroscopy and imaging of the arcuate fasciculus.

The arcuate fasciculus (AF) is a fiber pathway in the human brain relevant for language processes and has recently been characterized by means of diffusion tensor tractography. The observations made concerning the left and right hemisphere AF include a characterization of the trajectories and quantification of physical properties such as fractional anisotropy, DTI-based fiber density and volume. However, these observations were based on the diffusion of water, which is not particular to either the intra- or extra-axonal compartments, and thus its usefulness for tissue characterization is limited.

Targeted binding of PLA microparticles with lipid-PEG-tethered ligands.

Solid core polymeric particles are an attractive delivery vehicle as they can efficiently encapsulate drugs of different physical and chemical characteristics. However, the effective targeting of such particles for therapeutic purposes has been somewhat elusive. Here, we report novel polymeric particles comprised of poly(lactic acid) (PLA) with incorporated poly(ethylene glycol)-lipids (PEG-lipids).

Ex vivo identification of atherosclerotic plaque calcification by a 31P solid-state magnetic resonance imaging technique.

Calcified tissue is a common component of atherosclerotic plaques, and occurs most often in mature plaques. The process of calcification is a poorly understood risk factor that may contribute to a plaque's vulnerability to sudden rupture. In this study a solid-state imaging sequence, termed single-point imaging (SPI), was used to observe calcification directly in ex vivo atherosclerotic plaques.

Structure and orientation of pardaxin determined by NMR experiments in model membranes.

Pardaxins are a class of ichthyotoxic peptides isolated from fish mucous glands. Pardaxins physically interact with cell membranes by forming pores or voltage-gated ion channels that disrupt cellular functions. Here we report the high-resolution structure of synthetic pardaxin Pa4 in sodium dodecylphosphocholine micelles, as determined by (1)H solution NMR spectroscopy.

MSI-78, an analogue of the magainin antimicrobial peptides, disrupts lipid bilayer structure via positive curvature strain.

In this work, we present the first characterization of the cell lysing mechanism of MSI-78, an antimicrobial peptide. MSI-78 is an amphipathic alpha-helical peptide designed by Genaera Corporation as a synthetic analog to peptides from the magainin family. (31)P-NMR of mechanically aligned samples and differential scanning calorimetry (DSC) were used to study peptide-containing lipid bilayers.

Membrane composition determines pardaxin's mechanism of lipid bilayer disruption.

Pardaxin is a membrane-lysing peptide originally isolated from the fish Pardachirus marmoratus. The effect of the carboxy-amide of pardaxin (P1a) on bilayers of varying composition was studied using (15)N and (31)P solid-state NMR of mechanically aligned samples and differential scanning calorimetry (DSC). (15)N NMR spectroscopy of [(15)N-Leu(19)]P1a found that the orientation of the peptide's C-terminal helix depends on membrane composition.

An innovative procedure using a sublimable solid to align lipid bilayers for solid-state NMR studies.

Uniaxially aligned phospholipid bilayers are often used as model membranes to obtain structural details of membrane-associated molecules, such as peptides, proteins, drugs, and cholesterol. Well-aligned bilayer samples can be difficult to prepare and no universal procedure has been reported that orients all combinations of membrane-embedded components. In this study, a new method for producing mechanically aligned phospholipid bilayer samples using naphthalene, a sublimable solid, was developed.