Targeted in vivo extracellular matrix formation promotes neovascularization in a rodent model of myocardial infarction.

BackgroundThe extracellular matrix plays an important role in tissue regeneration. We investigated whether extracellular matrix protein fragments could be targeted with antibodies to ischemically injured myocardium to promote angiogenesis and myocardial repair.Methodology/principal findingsFour peptides, 2 derived from fibronectin and 2 derived from Type IV Collagen, were assessed for in vitro and in vivo tendencies for angiogenesis. Three of the four peptides--Hep I, Hep III, RGD--were identified and shown to increase endothelial cell attachment, proliferation, migration and cell activation in vitro. By chemically conjugating these peptides to an anti-myosin heavy chain antibody, the peptides could be administered intravenously and specifically targeted to the site of the myocardial infarction. When administered into Sprague-Dawley rats that underwent ischemia-reperfusion myocardial infarction, these peptides produced statistically significantly higher levels of angiogenesis and arteriogenesis 6 weeks post treatment.Conclusions/significanceWe demonstrated that antibody-targeted ECM-derived peptides alone can be used to sufficiently alter the extracellular matrix microenvironment to induce a dramatic angiogenic response in the myocardial infarct area. Our results indicate a potentially new non-invasive strategy for repairing damaged tissue, as well as a novel tool for investigating in vivo cell biology

Regression of atherosclerosis in cholesterol-fed rabbits: Effects of fish oil and verapamil

AbstractPrevious studies have shown that either fish oil or verapamil can attenuate the development of atherosclerosis in the lipid-fed rabbit. The present study was designed to evaluate the individual and combined effects of these two interventions on regression.Seventy New Zealand rabbits in seven groups (10 each) were fed a 0.3% cholesterol diet for 10 weeks. Control group C10 was then killed. Control group C20 was fed a 0.3% cholesterol diet and the other five groups were fed a normal diet for an additional 10 weeks. Group F in three treated groups received 2 ml/day of fish oil (Proto-Chol, eicosapentaenoic acid, 180 mg/ml and docosahexaenoic acid, 120 mg/ml) by gavage. Group V received verapamil, 2 g/1,000 ml drinking water, and group FV received both fish oil and verapamil for an additional 10 weeks. Group CF (control for fish oil) received 2 ml/day of water by gavage and group CV (control for verapamil) received water without gavage for an additional 10 weeks.The percent of aortic and pulmonary atherosclerosis was measured by planimetry of sudanophilic lesions. The percent of aortic lesions in the four control groups (C20, C10, CF and CV) was 57 ± 22, 40 ± 15, 40 ± 14 and 33 ± 25%, respectively. The fish oil or verapamil groups (F, V, FV) showed a significant reduction in aortic lesions: 15 ± 17%, p < 0.05; 16 ± 12%, p < 0.05; and 26 ± 24%, p = NS, respectively. The area of pulmonary artery lesions was significantly higher in the control group (CF, 24 ± 9%) than in group F (11 ± 9%, p < 0.05), group V (12 ± 9%, p < 0.05) and group FV (17 ± 14%, p = NS).These data demonstrate that either fish oil or verapamil can decrease atherosclerosis in cholesterol-fed rabbits placed on a normal diet. However, there was no additive effect of fish oil and verapamil. Although not statistically significant, there was a suggestive antagonistic effect between fish oil and verapamil

972-107 L-Arginine Decreases Infarct Size in Rats Exposed to Environmental Tobacco Smoke

We previously showed that environmental tobacco smoke (ETS) increased myocardial infarct size in a rat model of ischemia and reperfusion. If reduced reperfusion was caused by endothelial cell damage and increased vascular tone, we postulated that L-arginine (ARG) would increase nitric oxide and better protect the heart. 60 rats were randomly divided into 4 groups: ETS or Control (C) with and without ARG (2.25% ARG in drinking water). The ETS groups were exposed (4 Marlboro cigarettes per 15 minutes. 6 hours a day) for 6 weeks. During ETS-exposure, average air nicotine, carbon monoxide and total particulate concentrations were 1304 μg/m3, 78 ppm and 31 mg/m3, respectively. After 6 weeks, all rats were subjected to 35 min LAD occlusion (0) and 120 min reperfusion, with hemodynamic monitoring via the carotid artery. Aortic rings were harvested to evaluate vascular reactivity. Infarct size (infarct mass/risk area x 100%) decreased significantly in the ETS with ARG group compared to the ETS without ARG group. There were no significant differences among groups in heart rate (HR), systolic pressure (SP), and rate pressure product. Tlere were positive correlations between infarct size and heart rates from baseline to reperfusion 120 min (r = 0.4-0.6. p = 0.01-0.001). There was no relationship between vascular reactivity and infarct size.GroupNo. of RatsInf/LV (%)Inf/RA (%)0-35’HR (beats/m)0-35'SP (mmHg)Max Relax (%)C1125±351±6408±11120±784±11C+ ARG1025±252±3415±10103±11112±15ETS1034±464±6427±16108±8128±16ETS + ARG1122±3*42±6*410±17106±10127±18Values are Means±SEM*p&lt;0.05, p values from two-way ANOVAConclusionL-arginine decreases myocardial infarct size after ischemia and reperfusion in ETS-exposed rats. This effect does not appear to be secondary to alterations in hemodynamics

Preparation of Active Proteins, Vaccines and Pharmaceuticals as Fine Powders using Supercritical or Near-Critical Fluids

Supercritical or near-critical fluid processes for generating microparticles have enjoyed considerable attention in the past decade or so, with good success for substances soluble in supercritical fluids or organic solvents. In this review, we survey their application to the production of protein particles. A recently developed process known as CO2-assisted nebulization with a Bubble Dryer® (CAN-BD) has been demonstrated to have broad applicability to small-molecule as well as macromolecule substances (including therapeutic proteins). The principles of CAN-BD are discussed as well as the stabilization, micronization and drying of a wide variety of materials. More detailed case studies are presented for three proteins, two of which are of therapeutic interest: anti-CD4 antibody (rheumatoid arthritis), α1-antitrypsin (cystic fibrosis and emphysema), and trypsinogen (a model enzyme). Dry powders were formed in which stability and activity are maintained and which are fine enough to be inhaled and reach the deep lung. Enhancement of apparent activity after CAN-BD processing was also observed in some formulation and processing conditions

CMB observations from the CBI and VSA: A comparison of coincident maps and parameter estimation methods

We present coincident observations of the Cosmic Microwave Background (CMB) from the Very Small Array (VSA) and Cosmic Background Imager (CBI) telescopes. The consistency of the full datasets is tested in the map plane and the Fourier plane, prior to the usual compression of CMB data into flat bandpowers. Of the three mosaics observed by each group, two are found to be in excellent agreement. In the third mosaic, there is a 2 sigma discrepancy between the correlation of the data and the level expected from Monte Carlo simulations. This is shown to be consistent with increased phase calibration errors on VSA data during summer observations. We also consider the parameter estimation method of each group. The key difference is the use of the variance window function in place of the bandpower window function, an approximation used by the VSA group. A re-evaluation of the VSA parameter estimates, using bandpower windows, shows that the two methods yield consistent results.Comment: 10 pages, 6 figures. Final version. Accepted for publication in MNRA

The Atacama Cosmology Telescope: Cross Correlation with Planck maps

We present the temperature power spectrum of the Cosmic Microwave Background obtained by cross-correlating maps from the Atacama Cosmology Telescope (ACT) at 148 and 218 GHz with maps from the Planck satellite at 143 and 217 GHz, in two overlapping regions covering 592 square degrees. We find excellent agreement between the two datasets at both frequencies, quantified using the variance of the residuals between the ACT power spectra and the ACTxPlanck cross-spectra. We use these cross-correlations to calibrate the ACT data at 148 and 218 GHz, to 0.7% and 2% precision respectively. We find no evidence for anisotropy in the calibration parameter. We compare the Planck 353 GHz power spectrum with the measured amplitudes of dust and cosmic infrared background (CIB) of ACT data at 148 and 218 GHz. We also compare planet and point source measurements from the two experiments.Comment: 9 pages, 8 figure

The Atacama Cosmology Telescope: Two-Season ACTPol Lensing Power Spectrum

We report a measurement of the power spectrum of cosmic microwave background (CMB) lensing from two seasons of Atacama Cosmology Telescope Polarimeter (ACTPol) CMB data. The CMB lensing power spectrum is extracted from both temperature and polarization data using quadratic estimators. We obtain results that are consistent with the expectation from the best-fit Planck LCDM model over a range of multipoles L=80-2100, with an amplitude of lensing A_lens = 1.06 +/- 0.15 (stat.) +/- 0.06 (sys.) relative to Planck. Our measurement of the CMB lensing power spectrum gives sigma_8 Omega_m^0.25 = 0.643 +/- 0.054; including baryon acoustic oscillation scale data, we constrain the amplitude of density fluctuations to be sigma_8 = 0.831 +/- 0.053. We also update constraints on the neutrino mass sum. We verify our lensing measurement with a number of null tests and systematic checks, finding no evidence of significant systematic errors. This measurement relies on a small fraction of the ACTPol data already taken; more precise lensing results can therefore be expected from the full ACTPol dataset.Comment: 17 pages, 11 figures, to be submitted to Physical Review

The Atacama Cosmology Telescope: Sunyaev-Zel'dovich Selected Galaxy Clusters at 148 GHz from Three Seasons of Data

[Abridged] We present a catalog of 68 galaxy clusters, of which 19 are new discoveries, detected via the Sunyaev-Zel'dovich effect (SZ) at 148 GHz in the Atacama Cosmology Telescope (ACT) survey of 504 square degrees on the celestial equator. A subsample of 48 clusters within the 270 square degree region overlapping SDSS Stripe 82 is estimated to be 90% complete for M_500c > 4.5e14 Msun and 0.15 < z < 0.8. While matched filters are used to detect the clusters, the sample is studied further through a "Profile Based Amplitude Analysis" using a single filter at a fixed \theta_500 = 5.9' angular scale. This new approach takes advantage of the "Universal Pressure Profile" (UPP) to fix the relationship between the cluster characteristic size (R_500) and the integrated Compton parameter (Y_500). The UPP scalings are found to be nearly identical to an adiabatic model, while a model incorporating non-thermal pressure better matches dynamical mass measurements and masses from the South Pole Telescope. A high signal to noise ratio subsample of 15 ACT clusters is used to obtain cosmological constraints. We first confirm that constraints from SZ data are limited by uncertainty in the scaling relation parameters rather than sample size or measurement uncertainty. We next add in seven clusters from the ACT Southern survey, including their dynamical mass measurements based on galaxy velocity dispersions. In combination with WMAP7 these data simultaneously constrain the scaling relation and cosmological parameters, yielding \sigma_8 = 0.829 \pm 0.024 and \Omega_m = 0.292 \pm 0.025. The results include marginalization over a 15% bias in dynamical mass relative to the true halo mass. In an extension to LCDM that incorporates non-zero neutrino mass density, we combine our data with WMAP7+BAO+Hubble constant measurements to constrain \Sigma m_\nu < 0.29 eV (95% C. L.).Comment: 32 pages, 21 figures To appear in J. Cosmology and Astroparticle Physic

The Atacama Cosmology Telescope: Temperature and Gravitational Lensing Power Spectrum Measurements from Three Seasons of Data

We present the temperature power spectra of the cosmic microwave background (CMB) derived from the three seasons of data from the Atacama Cosmology Telescope (ACT) at 148 GHz and 218 GHz, as well as the cross-frequency spectrum between the two channels. We detect and correct for contamination due to the Galactic cirrus in our equatorial maps. We present the results of a number of tests for possible systematic error and conclude that any effects are not significant compared to the statistical errors we quote. Where they overlap, we cross-correlate the ACT and the South Pole Telescope (SPT) maps and show they are consistent. The measurements of higher-order peaks in the CMB power spectrum provide an additional test of the Lambda CDM cosmological model, and help constrain extensions beyond the standard model. The small angular scale power spectrum also provides constraining power on the Sunyaev-Zel'dovich effects and extragalactic foregrounds. We also present a measurement of the CMB gravitational lensing convergence power spectrum at 4.6-sigma detection significance.Comment: 21 pages; 20 figures, Submitted to JCAP, some typos correcte

Detection of the Power Spectrum of Cosmic Microwave Background Lensing by the Atacama Cosmology Telescope

We report the first detection of the gravitational lensing of the cosmic microwave background through a measurement of the four-point correlation function in the temperature maps made by the Atacama Cosmology Telescope. We verify our detection by calculating the levels of potential contaminants and performing a number of null tests. The resulting convergence power spectrum at 2-degree angular scales measures the amplitude of matter density fluctuations on comoving length scales of around 100 Mpc at redshifts around 0.5 to 3. The measured amplitude of the signal agrees with Lambda Cold Dark Matter cosmology predictions. Since the amplitude of the convergence power spectrum scales as the square of the amplitude of the density fluctuations, the 4-sigma detection of the lensing signal measures the amplitude of density fluctuations to 12%.Comment: 4 pages, 4 figures, replaced title and author list with version accepted by Physical Review Letters. Likelihood code can be downloaded from http://bccp.lbl.gov/~sudeep/ACTLensLike.htm