Inflammation reprogramming and immunomodulation: Next-generation treatments for atherosclerosis.

The current generation of highly successful atherosclerosis treatments, such as low-density lipoprotein (LDL)-cholesterol reduction, blood pressure management, and smoking cessation, has largely focused on ameliorating factors perceived to drive incident disease and its complications. The adverse contributions of these factors have typically been identified through epidemiological studies. The therapeutic strategies that arose in response focused on risk factors for disease development and tended to overlook the fact that patients already have established disease, by the time of presentation.

Deep learning based coronary vessels segmentation in X-ray angiography using temporal information.

Invasive coronary angiography (ICA) is the gold standard imaging modality during cardiac interventions. Accurate segmentation of coronary vessels in ICA is required for aiding diagnosis and creating treatment plans. Current automated algorithms for vessel segmentation face task-specific challenges, including motion artifacts and unevenly distributed contrast, as well as the general challenge inherent to X-ray imaging, which is the presence of shadows from overlapping organs in the background.

Patient-specific 3D coronary model in cardiac catheterisation laboratories.

Coronary artery disease is caused by the buildup of atherosclerotic plaque in the coronary arteries, affecting the blood supply to the heart, one of the leading causes of death around the world. X-ray coronary angiography is the most common procedure for diagnosing coronary artery disease, which uses contrast material and x-rays to observe vascular lesions. With this type of procedure, blood flow in coronary arteries is viewed in real-time, making it possible to detect stenoses precisely and control percutaneous coronary interventions and stent insertions.

Emerging opportunities to target inflammation: myocardial infarction and type 2 diabetes.

After myocardial infarction (MI), patients with type 2 diabetes have an increased rate of adverse outcomes, compared to patients without. Diabetes confers a 1.5-2-fold increase in early mortality and, importantly, this discrepancy has been consistent over recent decades, despite advances in treatment and overall survival.

Multi-organ single-cell RNA sequencing in mice reveals early hyperglycemia responses that converge on fibroblast dysregulation.

Diabetes causes a range of complications that can affect multiple organs. Hyperglycemia is an important driver of diabetes-associated complications, mediated by biological processes such as dysfunction of endothelial cells, fibrosis, and alterations in leukocyte number and function. Here, we dissected the transcriptional response of key cell types to hyperglycemia across multiple tissues using single-cell RNA sequencing (scRNA-seq) and identified conserved, as well as organ-specific, changes associated with diabetes complications.

Stratification of acute myocardial and endothelial cell injury, salvage index and final infarct size by systematic microRNA profiling in acute ST-elevation myocardial infarction.

Aim: Acute injury and subsequent remodelling responses to ST-segment elevation myocardial infarction (STEMI) are major determinants of clinical outcome. Current imaging and plasma biomarkers provide delayed readouts of myocardial injury and recovery. Here, we sought to systematically characterize all microRNAs (miRs) released during the acute phase of STEMI and relate miR release to magnetic resonance imaging (MRI) findings to predict acute and late responses to STEMI, from a single early blood sample.

HDL regulates TGFß-receptor lipid raft partitioning, restoring contractile features of cholesterol-loaded vascular smooth muscle cells.

Background: Cholesterol-loading of mouse aortic vascular smooth muscle cells (mVSMCs) downregulates , a master regulator of the contractile state downstream of TGFβ signaling. this results in transitioning from a contractile mVSMC to a macrophage-like state. This process likely occurs based on studies in mouse and human atherosclerotic plaques.

Trained immunity in diabetes and hyperlipidemia: Emerging opportunities to target cardiovascular complications and design new therapies.

Some metabolic diseases, such as diabetes and hyperlipidemia, are associated with a state of inflammation, which adversely affects cardiovascular health. Emerging evidence suggests that long-term hyperactivation of innate immune cells and their bone marrow progenitors, termed trained immunity, functions to accelerate atherosclerosis and its complications in cardiometabolic diseases. This review will focus on how trained immunity is established, particularly through metabolic and epigenetic reprogramming, to cause persistent and deleterious changes in immune cell function, even after the original stimulus has been corrected or removed.

10-channel phased-array coil for carotid wall MRI at 3T.

Background: Accurate assessment of plaque accumulation near the carotid bifurcation is important for the effective prevention and treatment of stroke. However, vessel and plaque delineation using MRI can be limited by low contrast-to-noise ratio (CNR) and long acquisition times. In this work, a 10-channel phased-array receive coil design for bilateral imaging of the carotid bifurcation using 3T MRI is proposed.

Prospects for Precision Medicine in Acute Myocardial Infarction: Patient-Level Insights into Myocardial Injury and Repair.

The past decade has seen a marked expansion in the understanding of the pathobiology of acute myocardial infarction and the systemic inflammatory response that it elicits. At the same time, a portfolio of tools has emerged to characterise some of these processes in vivo. However, in clinical practice, key decision making still largely relies on assessment built around the timing of the onset of chest pain, features on electrocardiograms and measurements of plasma troponin.

Acute Response in the Noninfarcted Myocardium Predicts Long-Term Major Adverse Cardiac Events After STEMI.

Background: Acute ST-segment elevation myocardial infarction (STEMI) has effects on the myocardium beyond the immediate infarcted territory. However, pathophysiologic changes in the noninfarcted myocardium and their prognostic implications remain unclear.

Objectives: The purpose of this study was to evaluate the long-term prognostic value of acute changes in both infarcted and noninfarcted myocardium post-STEMI.

Comparative and integrated analysis of plasma extracellular vesicle isolation methods in healthy volunteers and patients following myocardial infarction.

Plasma extracellular vesicle (EV) number and composition are altered following myocardial infarction (MI), but to properly understand the significance of these changes it is essential to appreciate how the different isolation methods affect EV characteristics, proteome and sphingolipidome. Here, we compared plasma EV isolated from platelet-poor plasma from four healthy donors and six MI patients at presentation and 1-month post-MI using ultracentrifugation (UC), polyethylene glycol precipitation, acoustic trapping, size-exclusion chromatography (SEC) and immunoaffinity capture. The isolated EV were evaluated by Nanoparticle Tracking Analysis (NTA), Western blot, transmission electron microscopy (TEM), an EV-protein array, untargeted proteomics (LC-MS/MS) and targeted sphingolipidomics (LC-MS/MS).

Automated 3D Whole-Heart Mesh Reconstruction From 2D Cine MR Slices Using Statistical Shape Model.

Cardiac magnetic resonance (CMR) imaging is the one of the gold standard imaging modalities for the diagnosis and characterization of cardiovascular diseases. The clinical cine protocol of the CMR typically generates high-resolution 2D images of heart tissues in a finite number of separated and independent 2D planes, which are appropriate for the 3D reconstruction of biventricular heart surfaces. However, they are usually inadequate for the whole-heart reconstruction, specifically for both atria.

Automated Torso Contour Extraction from Clinical Cardiac MR Slices for 3D Torso Reconstruction.

Whilst the electrocardiogram (ECG) is an essential tool for diagnosing cardiac electrical abnormalities, its characteristics are dependent on anatomical variability. Specifically variation in torso geometry affects relative positions of the leads with respect to the heart. We propose a novel pipeline that uses standard cardiac magnetic resonance images to reconstruct the torso and heart, and recreate the ECG considering torso and cardiac anatomy.

Neuropeptide-Y Levels in ST-Segment-Elevation Myocardial Infarction: Relationship With Coronary Microvascular Function, Heart Failure, and Mortality.

Background The sympathetic cotransmitter, neuropeptide Y (NPY), is released into the coronary sinus during ST-segment-elevation myocardial infarction and can constrict the coronary microvasculature. We sought to establish whether peripheral venous (PV) NPY levels, which are easy to obtain and measure, are associated with microvascular obstruction, myocardial recovery, and prognosis. Methods and Results NPY levels were measured immediately after primary percutaneous coronary intervention and compared with angiographic and cardiovascular magnetic resonance indexes of microvascular function.

Impaired phosphocreatine metabolism in white adipocytes promotes inflammation.

The mechanisms promoting disturbed white adipocyte function in obesity remain largely unclear. Herein, we integrate white adipose tissue (WAT) metabolomic and transcriptomic data from clinical cohorts and find that the WAT phosphocreatine/creatine ratio is increased and creatine kinase-B expression and activity is decreased in the obese state. In human in vitro and murine in vivo models, we demonstrate that decreased phosphocreatine metabolism in white adipocytes alters adenosine monophosphate-activated protein kinase activity via effects on adenosine triphosphate/adenosine diphosphate levels, independently of WAT beigeing.

Rapid neutrophil mobilization by VCAM-1+ endothelial cell-derived extracellular vesicles.

Aims: Acute myocardial infarction rapidly increases blood neutrophils (<2 h). Release from bone marrow, in response to chemokine elevation, has been considered their source, but chemokine levels peak up to 24 h after injury, and after neutrophil elevation. This suggests that additional non-chemokine-dependent processes may be involved.

A completely automated pipeline for 3D reconstruction of human heart from 2D cine magnetic resonance slices.

Cardiac magnetic resonance (CMR) imaging is a valuable modality in the diagnosis and characterization of cardiovascular diseases, since it can identify abnormalities in structure and function of the myocardium non-invasively and without the need for ionizing radiation. However, in clinical practice, it is commonly acquired as a collection of separated and independent 2D image planes, which limits its accuracy in 3D analysis. This paper presents a completely automated pipeline for generating patient-specific 3D biventricular heart models from cine magnetic resonance (MR) slices.