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The detection of the Epoch of Reionization (EoR) delay power spectrum using a 'foreground avoidance method' highly depends on the instrument chromaticity. The systematic effects induced by the radio telescope spread the foreground signal in the delay domain, which contaminates the EoR window theoretically observable. Applied to the Hydrogen Epoch of Reionization Array (HERA), this paper combines detailed electromagnetic and electrical simulations in order to model the chromatic effects of the instrument, and quantify its frequency and time responses. In particular, the effects of the analogue receiver, transmission cables, and mutual coupling are included. These simulations are able to accurately predict the intensity of the reflections occurring in the 150-m cable which links the antenna to the backend. They also show that electromagnetic waves can propagate from one dish to another one through large sections of the array due to mutual coupling. The simulated system time response is attenuated by a factor 104 after a characteristic delay which depends on the size of the array and on the antenna position. Ultimately, the system response is attenuated by a factor 105 after 1400 ns because of the reflections in the cable, which corresponds to characterizable ka-modes above 0.7 $h\,\,\rm {Mpc}^{-1}$ at 150 MHz. Thus, this new study shows that the detection of the EoR signal with HERA Phase I will be more challenging than expected. On the other hand, it improves our understanding of the telescope, which is essential to mitigate the instrument chromaticity.

ABSTRACT Cosmic strings are potential gravitational-wave (GW) sources that can be probed by pulsar timing arrays (PTAs). In this work we develop a detection algorithm for a GW burst from a cusp on a cosmic string, and apply it to Parkes PTA data. We find four events with a false alarm probability less than 1 per cent. However further investigation shows that all of these are likely to be spurious. As there are no convincing detections we place upper limits on the GW amplitude for different event durations. From these bounds we place limits on the cosmic string tension of Gμ ∼ 10−5, and highlight that this bound is independent from those obtained using other techniques. We discuss the physical implications of our results and the prospect of probing cosmic strings in the era of Square Kilometre Array.

Characterizing the epoch of reionization (EoR) at z 6 via the redshifted 21 cm line of neutral Hydrogen (H i) is critical to modern astrophysics and cosmology, and thus a key science goal of many current and planned low-frequency radio telescopes. The primary challenge to detecting this signal is the overwhelmingly bright foreground emission at these frequencies, placing stringent requirements on the knowledge of the instruments and inaccuracies in analyses. Results from these experiments have largely been limited not by thermal sensitivity but by systematics, particularly caused by the inability to calibrate the instrument to high accuracy. The interferometric bispectrum phase is immune to antenna-based calibration and errors therein, and presents an independent alternative to detect the EoR H i fluctuations while largely avoiding calibration systematics. Here, we provide a demonstration of this technique on a subset of data from the Hydrogen Epoch of Reionization Array (HERA) to place approximate constraints on the brightness temperature of the intergalactic medium (IGM). From this limited data, at z=7.7 we infer "1σ"upper limits on the IGM brightness temperature to be ≤ 316 "pseudo"mK at κ =0.33 "pseudo"h Mpc-1 (data-limited) and ≤ 1000 "pseudo"mK at κ =0.875 "pseudo"h Mpc-1 (noise-limited). The "pseudo"units denote only an approximate and not an exact correspondence to the actual distance scales and brightness temperatures. By propagating models in parallel to the data analysis, we confirm that the dynamic range required to separate the cosmic H i signal from the foregrounds is similar to that in standard approaches, and the power spectrum of the bispectrum phase is still data-limited (at 106 dynamic range) indicating scope for further improvement in sensitivity as the array build-out continues.

The key challenge in the observation of the redshifted 21-cm signal from cosmic reionization is its separation from the much brighter foreground emission. Such separation relies on the different spectral properties of the two components, although, in real life, the foreground intrinsic spectrum is often corrupted by the instrumental response, inducing systematic effects that can further jeopardize the measurement of the 21-cm signal. In this paper, we use Gaussian Process Regression to model both foreground emission and instrumental systematics in ∼2 h of data from the Hydrogen Epoch of Reionization Array. We find that a simple co-variance model with three components matches the data well, giving a residual power spectrum with white noise properties. These consist of an 'intrinsic' and instrumentally corrupted component with a coherence scale of 20 and 2.4 MHz, respectively (dominating the line-of-sight power spectrum over scales kâ ≤ 0.2 h cMpc-1) and a baseline-dependent periodic signal with a period of ∼1 MHz (dominating over kâ ∼0.4-0.8 h cMpc-1), which should be distinguishable from the 21-cm Epoch of Reionization signal whose typical coherence scale is ∼0.8 MHz.

In 21-cm cosmology, precision calibration is key to the separation of the neutral hydrogen signal from very bright but spectrally smooth astrophysical foregrounds. The Hydrogen Epoch of Reionization Array (HERA), an interferometer specialized for 21-cm cosmology and now under construction in South Africa, was designed to be largely calibrated using the self-consistency of repeated measurements of the same interferometric modes. This technique, known as redundant-baseline calibration resolves most of the internal degrees of freedom in the calibration problem. It assumes, however, on antenna elements with identical primary beams placed precisely on a redundant grid. In this work, we review the detailed implementation of the algorithms enabling redundant-baseline calibration and report results with HERA data.We quantify the effects of real-world non-redundancy and how they compare to the idealized scenario in which redundant measurements differ only in their noise realizations. Finally, we study how non-redundancy can produce spurious temporal structure in our calibration solutions-both in data and in simulations-and present strategies for mitigating that structure.

Radio frequency interference (RFI) is an ever-present limiting factor among radio telescopes even in the most remote observing locations. When looking to retain the maximum amount of sensitivity and reduce contamination for Epoch of Reionization studies, the identification and removal of RFI is especially important. In addition to improved RFI identification, we must also take into account computational efficiency of the RFI-Identification algorithm as radio interferometer arrays such as the Hydrogen Epoch of Reionization Array (HERA) grow larger in number of receivers. To address this, we present a deep fully convolutional neural network (DFCN) that is comprehensive in its use of interferometric data, where both amplitude and phase information are used jointly for identifying RFI. We train the network using simulated HERA visibilities containing mock RFI, yielding a known ‘ground truth’ data set for evaluating the accuracy of various RFI algorithms. Evaluation of the DFCN model is performed on observations from the 67 dish build-out, HERA-67, and achieves a data throughput of 1.6 × 105 HERA time-ordered 1024 channelled visibilities per hour per GPU. We determine that relative to an amplitude only network including visibility phase adds important adjacent time–frequency context which increases discrimination between RFI and non-RFI. The inclusion of phase when predicting achieves a recall of 0.81, precision of 0.58, and F2 score of 0.75 as applied to our HERA-67 observations.

Foreground power dominates the measurements of interferometers that seek a statistical detection of highly-redshifted H i emission from the Epoch of Reionization (EoR). The chromaticity of the instrument creates a boundary in the Fourier transform of frequency (proportional to k ∥) between spectrally smooth emission, characteristic of the strong synchrotron foreground (the "wedge"), and the spectrally structured emission from H i in the EoR (the "EoR window"). Faraday rotation can inject spectral structure into otherwise smooth polarized foreground emission, which through instrument effects or miscalibration could possibly pollute the EoR window. For instruments pursuing a "foreground avoidance" strategy of simply measuring in the EoR window, and not attempting to model and remove foregrounds, as is the plan for the first stage of the Hydrogen Epoch of Reionization Array (HERA), characterizing the intrinsic instrument polarization response is particularly important. Using data from the HERA 19-element commissioning array, we investigate the polarization response of this new instrument in the power-spectrum domain. We perform a simple image-based calibration based on the unpolarized diffuse emission of the Global Sky Model, and show that it achieves qualitative redundancy between the nominally redundant baselines of the array and reasonable amplitude accuracy. We construct power spectra of all fully polarized coherencies in all pseudo-Stokes parameters, and discuss the achieved isolation of foreground power due to the intrinsic spectral smoothness of the foregrounds, the instrument chromaticity, and the calibration. We compare to simulations based on an unpolarized diffuse sky model and detailed electromagnetic simulations of the dish and feed, confirming that in Stokes I, the calibration does not add significant spectral structure beyond that expected from the interferometer array configuration and the modeled primary beam response. Furthermore, this calibration is stable over the 8 days of observations considered. Excess power is seen in the power spectra of the linear polarization Stokes parameters, which is not easily attributable to leakage via the primary beam, and results from some combination of residual calibration errors and actual polarized emission. Stokes V is found to be highly discrepant from the expectation of zero power, strongly pointing to the need for more accurate polarized calibration.

Spectral structures due to the instrument response is the current limiting factor for the experiments attempting to detect the redshifted 21 cm signal from the Epoch of Reionization (EoR). Recent advances in the delay spectrum methodology for measuring the redshifted 21 cm EoR power spectrum brought new attention to the impact of an antenna’s frequency response on the viability of making this challenging measurement. The delay spectrum methodology provides a somewhat straightforward relationship between the time-domain response of an instrument that can be directly measured and the power spectrum modes accessible to a 21 cm EoR experiment. In this paper, we derive the explicit relationship between antenna reflection coefficient (S11) measurements made by a Vector Network Analyzer (VNA) and the extent of additional foreground contaminations in delay space. In the light of this mathematical framework, we examine the chromaticity of a prototype antenna element that will constitute the Hydrogen Epoch of Reionization Array (HERA) between 100 and 200 MHz. These reflectometry measurements exhibit additional structures relative to electromagnetic simulations, but we find that even without any further design improvement, such an antenna element will support measuring spatial k modes with line-of-sight components of k∥ > 0.2h Mpc− 1. We also find that when combined with the powerful inverse covariance weighting method used in optimal quadratic estimation of redshifted 21 cm power spectra the HERA prototype elements can successfully measure the power spectrum at spatial modes as low as k∥ > 0.1h Mpc− 1. This work represents a major step toward understanding the HERA antenna element and highlights a straightforward method for characterizing instrument response for future experiments designed to detect the 21 cm EoR power spectrum.

The observation of the global 21 cm signal produced by neutral hydrogen gas in the intergalactic medium (IGM) during the Dark Ages, Cosmic Dawn, and Epoch of Reionization requires measurements with extremely well-calibrated wideband radiometers. We describe the design and characterization of the Mapper of the IGM Spin Temperature (MIST), which is a new ground-based, single-antenna, global 21 cm experiment. The design of MIST was guided by the objectives of avoiding systematics from an antenna ground plane and cables around the antenna, as well as maximizing the instrument's on-sky efficiency and portability for operations at remote sites. We have built two MIST instruments, which observe in the range 25–105 MHz. For the 21 cm signal, this frequency range approximately corresponds to redshifts 55.5 > z > 12.5, encompassing the Dark Ages and Cosmic Dawn. The MIST antenna is a horizontal blade dipole of 2.42 m in length, 60 cm in width, and 52 cm in height above the ground. This antenna operates without a metal ground plane. The instruments run on 12 V batteries and have a maximum power consumption of 17 W. The batteries and electronics are contained in a single receiver box located under the antenna. We present the characterization of the instruments using electromagnetic simulations and lab measurements. We also show sample sky measurements from recent observations at remote sites in California, Nevada, and the Canadian High Arctic. These measurements indicate that the instruments perform as expected. Detailed analyses of the sky measurements are left for future work. [ABSTRACT FROM AUTHOR]

The main goal of pulsar timing array experiments is to detect correlated signals such as nanohertz-frequency gravitational waves. Pulsar timing data collected in dense monitoring campaigns can also be used to study the stars themselves, their binary companions, and the intervening ionized interstellar medium. Timing observations are extraordinarily sensitive to changes in path-length between the pulsar and the Earth, enabling precise measurements of the pulsar positions, distances and velocities, and the shapes of their orbits. Here we present a timing analysis of 25 pulsars observed as part of the Parkes Pulsar Timing Array (PPTA) project over time spans of up to 24 yr. The data are from the second data release of the PPTA, which we have extended by including legacy data. We make the first detection of Shapiro delay in four Southern pulsars (PSRs J1017−7156, J1125−6014, J1545−4550, and J1732−5049), and of parallax in six pulsars. The prominent Shapiro delay of PSR J1125−6014 implies a neutron star mass of Mp = 1.5 ± 0.2 M⊙ (68 per cent credibility interval). Measurements of both Shapiro delay and relativistic periastron advance in PSR J1600−3053 yield a large but uncertain pulsar mass of |$M_p = 2.06^{+0.44}_{-0.41}$|  M⊙ (68 per cent credibility interval). We measure the distance to PSR J1909−3744 to a precision of 10 lyr, indicating that for gravitational wave periods over a decade, the pulsar provides a coherent baseline for pulsar timing array experiments. [ABSTRACT FROM AUTHOR]

Pulsar timing array projects measure the pulse arrival times of millisecond pulsars for the primary purpose of detecting nanohertz-frequency gravitational waves. The measurements include contributions from a number of astrophysical and instrumental processes, which can either be deterministic or stochastic. It is necessary to develop robust statistical and physical models for these noise processes because incorrect models diminish sensitivity and may cause a spurious gravitational wave detection. Here we characterize noise processes for the 26 pulsars in the second data release of the Parkes Pulsar Timing Array using Bayesian inference. In addition to well-studied noise sources found previously in pulsar timing array data sets such as achromatic timing noise and dispersion measure variations, we identify new noise sources including time-correlated chromatic noise that we attribute to variations in pulse scattering. We also identify 'exponential dip' events in four pulsars, which we attribute to magnetospheric effects as evidenced by pulse profile shape changes observed for three of the pulsars. This includes an event in PSR J1713+0747, which had previously been attributed to interstellar propagation. We present noise models to be used in searches for gravitational waves. We outline a robust methodology to evaluate the performance of noise models and identify unknown signals in the data. The detection of variations in pulse profiles highlights the need to develop efficient profile domain timing methods. [ABSTRACT FROM AUTHOR]

Cosmic strings are potential gravitational-wave (GW) sources that can be probed by pulsar timing arrays (PTAs). In this work we develop a detection algorithm for a GW burst from a cusp on a cosmic string, and apply it to Parkes PTA data. We find four events with a false alarm probability less than 1 per cent. However further investigation shows that all of these are likely to be spurious. As there are no convincing detections we place upper limits on the GW amplitude for different event durations. From these bounds we place limits on the cosmic string tension of G μ ∼ 10−5, and highlight that this bound is independent from those obtained using other techniques. We discuss the physical implications of our results and the prospect of probing cosmic strings in the era of Square Kilometre Array. [ABSTRACT FROM AUTHOR]

The fast radio burst (FRB) population is observationally divided into sources that have been observed to repeat and those that have not. There is tentative evidence that the bursts from repeating sources have different properties than the non-repeating ones. In order to determine the occurrence rate of repeating sources and characterize the nature of repeat emission, we have been conducting sensitive searches for repetitions from bursts detected with the Australian Square Kilometre Array Pathfinder (ASKAP) with the 64-m Parkes radio telescope, using the recently commissioned Ultra-wideband Low (UWL) receiver system, over a band spanning 0.7–4.0 GHz. We report the detection of a repeat burst from the source of FRB 20190711A. The detected burst is 1 ms wide and has a bandwidth of just 65 MHz. We find no evidence of any emission in the remaining part of the 3.3 GHz UWL band. While the emission bandwidths of the ASKAP and UWL bursts show ν−4 scaling consistent with a propagation effect, the spectral occupancy is inconsistent with diffractive scintillation. This detection rules out models predicting broad-band emission from the FRB 20190711A source and puts stringent constraints on the emission mechanism. The low spectral occupancy highlights the importance of sub-banded search methods in detecting FRBs. [ABSTRACT FROM AUTHOR]

Experiments that pursue detection of signals from the Epoch of Reionization (EoR) are relying on spectral smoothness of source spectra at low frequencies. This article empirically explores the effect of foreground spectra on EoR experiments by measuring high-resolution full-polarization spectra for the 586 brightest unresolved sources in one of the MWA EoR fields using 45 h of observation. A novel peeling scheme is used to subtract 2500 sources from the visibilities with ionospheric and beam corrections, resulting in the deepest, confusion-limited MWA image so far. The resulting spectra are found to be affected by instrumental effects, which limit the constraints that can be set on source-intrinsic spectral structure. The sensitivity and power-spectrum of the spectra are analysed, and it is found that the spectra of residuals are dominated by PSF sidelobes from nearby undeconvolved sources. We release a catalogue describing the spectral parameters for each measured source., Astronomy

We present the 21 cm power spectrum analysis approach of the Murchison Widefield Array Epoch of Reionization project. In this paper, we compare the outputs of multiple pipelines for the purpose of validating statistical limits cosmological hydrogen at redshifts between 6 and 12. Multiple, independent, data calibration and reduction pipelines are used to make power spectrum limits on a fiducial night of data. Comparing the outputs of imaging and power spectrum stages highlights differences in calibration, foreground subtraction and power spectrum calculation. The power spectra found using these different methods span a space defined by the various tradeoffs between speed, accuracy, and systematic control. Lessons learned from comparing the pipelines range from the algorithmic to the prosaically mundane; all demonstrate the many pitfalls of neglecting reproducibility. We briefly discuss the way these different methods attempt to handle the question of evaluating a significant detection in the presence of foregrounds., Astronomy

HDLs carry sphingosine-1-phosphate (S1P) and stimulate signaling pathways in different cells including macrophages and endothelial cells, involved in atherosclerotic plaque development. HDL signaling via S1P relies on the HDL receptor scavenger receptor class B, type I (SR-B1) and the sphingosine-1-phosphate receptor 1 (S1PR1), which interact when both are heterologously overexpressed in the HEK293 cell line. In this study, we set out to test if SR-B1 and S1PR1 interacted in primary murine macrophages in culture and atherosclerotic plaques. We used knock-in mice that endogenously expressed S1PR1 tagged with eGFP-(S1pr1 eGFP/eGFP mice), combined with proximity ligation analysis to demonstrate that HDL stimulates the physical interaction between SR-B1 and S1PR1 in primary macrophages, that this is dependent on HDL-associated S1P and can be blocked by an inhibitor of SR-B1's lipid transfer activity or an antagonist of S1PR1. We also demonstrate that a synthetic S1PR1-selective agonist, SEW2871, stimulates the interaction between SR-B1 and S1PR1 and that this was also blocked by an inhibitor of SR-B1's lipid transport activity. Furthermore, we detected abundant SR-B1/S1PR1 complexes in atherosclerotic plaques of S1pr1 eGFP/eGFP mice that also lacked apolipoprotein E. Treatment of mice with the S1PR1 antagonist, Ex26, for 12 h disrupted the SR-B1-S1PR1 interaction in atherosclerotic plaques. These findings demonstrate that SR-B1 and S1PR1 form ligand-dependent complexes both in cultured primary macrophages and within atherosclerotic plaques in mice and provide mechanistic insight into how SR-B1 and S1PR1 participate in mediating HDL signaling to activate atheroprotective responses in macrophages., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

We develop a process of image-plane self-calibration for interferometric imaging data. The process is based on shape-orientation-size (SOS) conservation for the principal triangle in an image generated from the three fringes made from a triad of receiving elements, in situations where interferometric phase errors can be factorized into element-based terms. The basis of the SOS conservation principle is that, for a three-element array, the only possible image corruption due to an element-based phase screen is a tilt of the aperture plane, leading to a shift in the image plane. Thus, an image made from any three-element interferometer represents a true image of the source brightness, modulo an unknown translation. Image-plane self-calibration entails deriving the unknown translations for each triad image via cross-correlation of the observed triad image with a model image of the source brightness. After correcting for these independent shifts, and summing the aligned triad images, a good image of the source brightness is generated from the full array, recovering source structure at diffraction-limited resolution. The process is iterative, using improved source models based on previous iterations. We demonstrate the technique in a high signal-to-noise context, and include a configuration based on radio astronomical facilities, and simple models of double sources. We show that the process converges for the simple models considered, although convergence is slower than for aperture-plane self-calibration for large- N arrays. As currently implemented, the process is most relevant for arrays with a small number of elements. More generally, the technique provides geometric insight into closure phase and the self-calibration process. The technique is generalizable to non-astronomical interferometric imaging applications across the electromagnetic spectrum.

A transfer hydrosilylation of ketones employing silyl formates as hydrosilane surrogates under mild conditions is presented. A total of 24 examples of ketones have been successfully converted to their corresponding silyl ethers with 61-99% yields in the presence of a PN H P-based ruthenium catalyst and silyl formate reagent. The crucial role of the ligand for the transformation is demonstrated.

The discovery of magnetic fields close to the M87 black hole using very long baseline interferometry by the Event Horizon Telescope collaboration utilized the novel concept of "closure traces," that are immune to element-based aberrations. We take a fundamentally new approach to this promising tool of polarimetric very long baseline interferometry, using ideas from the geometric phase and gauge theories. The multiplicative distortion of polarized signals at the individual elements are represented as gauge transformations by general 2×2 complex matrices, so the closure traces now appear as gauge-invariant quantities. We apply this formalism to polarimetric interferometry and generalize it to any number of interferometer elements. Our approach goes beyond existing studies in the following respects: (1) we use triangular combinations of correlations as basic building blocks of invariants, (2) we use well-known symmetry properties of the Lorentz group to transparently identify a complete and independent set of invariants, and (3) we do not need autocorrelations, which are susceptible to large systematic biases, and therefore unreliable. This set contains all the information, immune to corruption, available in the interferometer measurements, thus providing important robust constraints for interferometric studies.

A cosmological first-order phase transition is expected to produce a stochastic gravitational wave background. If the phase transition temperature is on the MeV scale, the power spectrum of the induced stochastic gravitational waves peaks around nanohertz frequencies, and can thus be probed with high-precision pulsar timing observations. We search for such a stochastic gravitational wave background with the latest data set of the Parkes Pulsar Timing Array. We find no evidence for a Hellings-Downs spatial correlation as expected for a stochastic gravitational wave background. Therefore, we present constraints on first-order phase transition model parameters. Our analysis shows that pulsar timing is particularly sensitive to the low-temperature (T∼1-100  MeV) phase transition with a duration (β/H_{*})^{-1}∼10^{-2}-10^{-1} and therefore can be used to constrain the dark and QCD phase transitions.

Detecting neutral hydrogen (H i) via the 21 cm line emission from the intergalactic medium at z≳6 has been identified as one of the most promising probes of the epoch of cosmic reionization-a major phase transition of the Universe. However, these studies face severe challenges imposed by the bright foreground emission from cosmic objects. Current techniques require precise instrumental calibration to separate the weak H i line signal from the foreground continuum emission. We propose to mitigate this calibration requirement by using measurements of the interferometric bispectrum phase. The bispectrum phase is unaffected by antenna-based direction-independent calibration errors and hence for a compact array it depends on the sky brightness distribution only (subject to the usual thermal-like noise). We show that the bispectrum phase of the foreground synchrotron continuum has a characteristically smooth spectrum relative to the cosmological line signal. The two can be separated effectively by exploiting this spectral difference using Fourier techniques, while eliminating the need for precise antenna-based calibration of phases introduced by the instrument, and the ionosphere, inherent in existing approaches. Using fiducial models for continuum foregrounds, and for the cosmological H i signal, we show the latter should be detectable in bispectrum phase spectra, with reasonable significance at |k_{∥}|≳0.5h  Mpc^{-1}, using existing instruments. Our approach will also benefit other H i intensity mapping experiments that face similar challenges, such as those measuring baryon acoustic oscillations (BAO).

Macrophage lipoprotein lipase (LPL) induces lipid accumulation and promotes atherosclerosis. However, the effects of lipoprotein hydrolysis products generated by LPL on macrophage-derived foam cell formation are not clearly understood. Thus, we analyzed the transcriptomic response to hydrolysis products via microarray analyses on RNA isolated from human THP-1 macrophages incubated with total lipoprotein hydrolysis products generated by LPL. The expression of 183 transcripts was significantly upregulated and 133 transcripts were significantly downregulated. Bioinformatics analyses revealed that there was a significant over-representation of genes involved in cell cycling, stress response, type I interferon signaling, cellular metal ion homeostasis, sterol metabolism, and nuclease activity. Interestingly, transcripts for 63 small nucleolar RNA were significantly upregulated. We verified the microarray data by quantitative real-time PCR and found that the expression of SNORA56, as well as the expression of genes associated with the cell cycle (PCNA and DKC1 variant 3), stress response (ATF3), type I interferon signaling (IFITM1), and lipid metabolism (CD36 and PLIN2) were significantly affected by LPL hydrolysis products. To determine if the free fatty acid (FFA) component of total lipoprotein hydrolysis products is sufficient to alter the expression of these genes, THP-1 macrophages were also incubated with the total FFA or individual classes of the FFA component. The gene regulation by the FFA component did not mimic that of the hydrolysis products, suggesting that the regulation of gene expression in THP-1 macrophages depends on the specific combination and concentration of lipid species present in the hydrolysis products, and not solely on FFA.

Lipoprotein lipase (LPL) is an extracellular lipase that primarily hydrolyzes triglycerides within circulating lipoproteins. Macrophage LPL contributes to atherogenesis, but the mechanisms behind it are poorly understood. We hypothesized that the products of lipoprotein hydrolysis generated by LPL promote atherogenesis by inhibiting the cholesterol efflux ability by macrophages. To test this hypothesis, we treated human THP-1 macrophages with total lipoproteins that were hydrolyzed by LPL and we found significantly reduced transcript levels for the cholesterol transporters ATP binding cassette transporter A1 (ABCA1), ABCG1, and scavenger receptor BI. These decreases were likely due to significant reductions for the nuclear receptors liver-X-receptor-α, peroxisome proliferator activated receptor (PPAR)-α, and PPAR-γ. We prepared a mixture of free fatty acids (FFA) that represented the ratios of FFA species within lipoprotein hydrolysis products, and we found that the FFA mixture also significantly reduced cholesterol transporters and nuclear receptors. Finally, we tested the efflux of cholesterol from THP-1 macrophages to apolipoprotein A-I, and we found that the treatment of THP-1 macrophages with the FFA mixture significantly attenuated cholesterol efflux. Overall, these data show that the FFA component of lipoprotein hydrolysis products generated by LPL may promote atherogenesis by inhibiting cholesterol efflux, which partially explains the pro-atherogenic role of macrophage LPL., (Copyright © 2014 Elsevier Inc. All rights reserved.)