Novel functional atrial fibrillation risk genes and pathways identified from coexpression analyses in human left atria.

Background: Genomewide association studies have associated >100 genetic loci with atrial fibrillation (AF), but establishing causal genes contributing to AF remains challenging.

Objective: The purpose of this study was to determine candidate novel causal genes and mechanistic pathways associated with AF risk loci by incorporating gene expression and coexpression analyses and to provide a resource for functional studies and targeting of AF-associated genes.

Methods: Cis-expression quantitative trait loci were identified for candidate genes near AF risk variants in human left atrial tissues.

Risk factors, transcriptomics, and outcomes of myocardial injury following lower extremity revascularization.

Myocardial injury after non-cardiac surgery (MINS) is common. We investigated the incidence and outcomes of MINS, and mechanistic underpinnings using pre-operative whole blood gene expression profiling in a prospective cohort study of individuals undergoing lower extremity revascularization (LER) for peripheral artery disease (PAD). Major adverse cardiovascular and limb events (MACLE) were defined as a composite of death, myocardial infarction, stroke, major lower extremity amputation or reoperation.

Cardiac Pressure Overload Decreases ETV1 Expression in the Left Atrium, Contributing to Atrial Electrical and Structural Remodeling.

Background: Elevated intracardiac pressure attributable to heart failure induces electrical and structural remodeling in the left atrium (LA) that begets atrial myopathy and arrhythmias. The underlying molecular pathways that drive atrial remodeling during cardiac pressure overload are poorly defined. The purpose of this study is to characterize the response of the ETV1 (ETS translocation variant 1) signaling axis in the LA during cardiac pressure overload in humans and mouse models and explore the role of ETV1 in atrial electrical and structural remodeling.

Exploratory MRI measures after intravenous autologous culture-expanded mesenchymal stem cell transplantation in multiple sclerosis.

Background: Mesenchymal stem cells (MSC) have immunomodulatory and neuro-protective properties and are being studied for treatment of multiple sclerosis (MS). Tractography-based diffusion tensor imaging (DTI), cortical thickness (Cth) and T2 lesion volume (T2LV) can provide insight into treatment effects.

Objective: The objective of this study was to analyse the effects of MSC transplantation in MS on exploratory MRI measures.

Total variation minimization approach in in-line x-ray phase-contrast tomography.

The reconstruction problem in in-line X-ray Phase-Contrast Tomography is usually approached by solving two independent linearized sub-problems: phase retrieval and tomographic reconstruction. Both problems are often ill-posed and require the use of regularization techniques that lead to artifacts in the reconstructed image. We present a novel reconstruction approach that solves two coupled linear problems algebraically.

Phase retrieval in in-line x-ray phase contrast imaging based on total variation minimization.

State-of-the-art techniques for phase retrieval in propagation based X-ray phase-contrast imaging are aiming to solve an underdetermined linear system of equations. They commonly employ Tikhonov regularization - an L2-norm regularized deconvolution scheme - despite some of its limitations. We present a novel approach to phase retrieval based on Total Variation (TV) minimization.

Characterization of an x-ray phase contrast imaging system based on the miniature synchrotron MIRRORCLE-6X.

Purpose: The implementation of in-line x-ray phase contrast imaging (PCI) for soft-tissue patient imaging is hampered by the lack of a bright and spatially coherent x-ray source that fits into the hospital environment. This article provides a quantitative characterization of the phase-contrast enhancement of a PCI system based on the miniature synchrotron technology MIRRORCLE-6X.

Methods: The phase-contrast effect was measured using an edge response of a plexiglass plate as a function of the incident angle of radiation.

Nonenhanced methods for lower-extremity MRA: a phantom study examining the effects of stenosis and pathologic flow waveforms at 1.5T.

Purpose: To evaluate the signal properties of 2D time of flight (TOF), quiescent-interval single-shot (QISS), ECG-gated 3D fast spin-echo (FBI), and ungated 3D fast spin-echo ghost (Ghost) magnetic resonance angiography (MRA) over a range of flow velocities in a pulsatile flow phantom with a 50% diameter stenosis at 1.5T.

Materials And Methods: Blood-mimicking fluid was pumped at eight peak flow velocities through a stenotic region in triphasic and monophasic waveforms.

Fully automated reconstruction of ungated ghost magnetic resonance angiograms.

Purpose: To completely automate the reconstruction process during noncardiac-gated unenhanced ghost magnetic resonance angiography (MRA).

Materials And Methods: Ungated unenhanced ghost MRA of the calf was performed in 16 volunteers. K-means and fuzzy c-means (FCM) clustering algorithms using prominent image features were applied to automatically create angiograms of the calf in volunteers undergoing ungated ghost MRA.

Multipurpose furnace for in situ studies of polycrystalline materials using synchrotron radiation.

We report a multipurpose furnace designed for studies using synchrotron radiation on polycrystalline materials, namely, metals, ceramics, and (semi)crystalline polymers. The furnace has been designed to carry out three-dimensional (3D) x-ray diffraction measurements but can also be used for other types of synchrotron radiation research. The furnace has a very low thermal gradient across the specimen (<0.

Apolipoprotein C-I binds free fatty acids and reduces their intracellular esterification.

Mice that overexpress human apolipoprotein C-I (apoC-I) homozygously (APOC1(+/+) mice) are protected against obesity and show cutaneous abnormalities. Although these effects can result from our previous observation that apoC-I inhibits FFA generation by LPL, we have also found that apoC-I impairs the uptake of a FFA analog in adipose tissue. In this study, we tested the hypothesis that apoC-I interferes with cellular FFA uptake independent of LPL activity.

Apolipoprotein CI aggravates atherosclerosis development in ApoE-knockout mice despite mediating cholesterol efflux from macrophages.

Objective: Apolipoprotein CI (apoCI) is expressed in the liver and in macrophages, and has several roles in lipid metabolism. Since macrophage apoCI expression might affect macrophage lipid homeostasis and atherosclerotic lesion development locally in the arterial wall, we investigated the effect of both systemic and macrophage apoCI on atherosclerotic lesion development.

Methods And Results: To investigate whether physiological expression levels of apoCI affect atherosclerosis development, we first assessed the effect of systemic endogenous apoCI expression on atherosclerosis in apoe-/- apoc1+/+ as compared to apoe-/- apoc1-/- mice at 26 weeks of age.

Cholesteryl ester transfer protein decreases high-density lipoprotein and severely aggravates atherosclerosis in APOE*3-Leiden mice.

Objective: The role of cholesteryl ester transfer protein (CETP) in the development of atherosclerosis is still undergoing debate. Therefore, we evaluated the effect of human CETP expression on atherosclerosis in APOE*3-Leiden (E3L) mice with a humanized lipoprotein profile.

Methods And Results: E3L mice were crossbred with human CETP transgenic mice.

Anti-atherosclerotic effect of amlodipine, alone and in combination with atorvastatin, in APOE*3-Leiden/hCRP transgenic mice.

We investigated the pleiotropic effects of a calcium antagonist (amlodipine) on early atherosclerosis development in the presence and absence of an HMG-CoA-reductase inhibitor (atorvastatin) in apolipoprotein E*3-Leiden/human C-reactive protein (E3L/CRP) transgenic mice. Male E3L/CRP transgenic mice were fed a cholesterol-containing diet either with or without amlodipine and/or atorvastatin. After 31 weeks, atherosclerosis in the aortic root area was quantified.

Absence of an atheroprotective effect of the garlic powder printanor in APOE*3-Leiden transgenic mice.

Numerous animal studies have reported that garlic can protect against atherosclerosis. However, a comparable number of studies do not support this observation. This contradiction may result from differences in study design, use of different animal models, and use of different garlic formulations and preparations.

Effect of low dose atorvastatin versus diet-induced cholesterol lowering on atherosclerotic lesion progression and inflammation in apolipoprotein E*3-Leiden transgenic mice.

Objective: To evaluate whether low-dose atorvastatin suppresses atherosclerotic lesion progression and inflammation in apolipoprotein E*3 (apoE*3)-Leiden mice beyond its cholesterol-lowering effect.

Methods And Results: ApoE*3-Leiden mice were fed a high-cholesterol (HC) diet until mild atherosclerotic lesions had formed. Subsequently, HC diet feeding was continued or mice received HC supplemented with 0.

Genetic deletion of tissue-type plasminogen activator (t-PA) in APOE3-Leiden mice reduces progression of cholesterol-induced atherosclerosis.

During recent years it has become increasingly recognized that the plasmin activation system is involved in the development of atherosclerosis. In this paper, we have studied the contribution of the plasminogen activation system in the development of atherosclerosis by cross-breeding apoE3-Leiden mice, which have a human-like lipid profile, with mice deficient in PAI-1 (plasminogen-activator inhibitor-1), u-PA (urokinase plasminogen activator), and t-PA (tissue plasminogen activator). Genetic compound offspring was used to evaluate the progression of atherosclerotic lesions after they were fed a variant atherogenic diet for 12 weeks.