Pediatric hypertrophic cardiomyopathy caused by a novel TNNI3 variant.

TNNI3 is a gene that causes hypertrophic cardiomyopathy (HCM). A 14-year-old girl who was diagnosed with nonobstructive HCM presented with cardiopulmonary arrest due to ventricular fibrillation. Genetic testing revealed a novel de novo heterozygous missense variant in TNNI3, NM_000363.

PRELP secreted from mural cells protects the function of blood brain barrier through regulation of endothelial cell-cell integrity.

Proline/arginine-rich end leucine-rich repeat protein (PRELP), is a small secreted proteoglycan expressed by pericytes and vascular smooth muscle cells surrounding the brain vasculature of adult mouse. We utilised a knockout ( ) mouse model to interrogate vasculature integrity in the brain alongside performing in vitro assays to characterise PRELP application to endothelial cells lines. Our findings were supplemented with RNA expression profiling to elucidate the mechanism of how PRELP maintains neurovasculature function.

Potential of non-contrast stress T1 mapping for the assessment of myocardial injury in hypertrophic cardiomyopathy.

Background: Ischemia of the hypertrophied myocardium due to microvascular dysfunction is related to a worse prognosis in hypertrophic cardiomyopathy (HCM). Stress and rest T1 mapping without contrast agents can be used to assess myocardial blood flow. Herein, we evaluated the potential of non-contrast stress T1 mapping in assessing myocardial injury in patients with HCM.

Expert Consensus on the Clinical Use of Pulse Wave Velocity in Asia.

Arterial stiffness is a progressive aging process that predicts cardiovascular disease. Pulse wave velocity (PWV) has emerged as a noninvasive, valid, and reliable measure of arterial stiffness and an independent risk predictor for adverse outcomes. However, up to now, PWV measurement has mostly been used as a tool for risk prediction and has not been widely used in clinical practice.

Repression of the PRELP gene is relieved by histone deacetylase inhibitors through acetylation of histone H2B lysine 5 in bladder cancer.

Background: Proline/arginine-rich end leucine-rich repeat protein (PRELP) is a member of the small leucine-rich proteoglycan family of extracellular matrix proteins, which is markedly suppressed in the majority of early-stage epithelial cancers and plays a role in regulating the epithelial-mesenchymal transition by altering cell-cell adhesion. Although PRELP is an important factor in the development and progression of bladder cancer, the mechanism of PRELP gene repression remains unclear.

Results: Here, we show that repression of PRELP mRNA expression in bladder cancer cells is alleviated by HDAC inhibitors (HDACi) through histone acetylation.

Biophysical Characterization of the Contribution of the Fab Region to the IgG-FcγRIIIa Interaction.

The cell-surface receptor FcγRIIIa is crucial to the efficacy of therapeutic antibodies as well as the immune response. The interaction of the Fc region of IgG molecules with FcγRIIIa has been characterized, but until recently, it was thought that the Fab regions were not involved in the interaction. To evaluate the influence of the Fab regions in a biophysical context, we carried out surface plasmon resonance analyses using recombinant FcγRIIIa ligands.

Performance of Hybrid Imaging in the Diagnosis of Coronary Artery Disease.

Single-photon emission computed tomography (SPECT) and computed tomography coronary angiography (CTCA) are usually performed independently in patients with suspected coronary artery disease. We assessed the hypothesis that hybrid SPECT/CTCA imaging results in higher diagnostic accuracy than either method alone, particularly in cases presenting with high levels of coronary calcification. A total of 243 major coronary vessels in 81 patients with known or suspected coronary artery disease were screened using SPECT with semiconductor detectors and CTCA with 256-detector row computed tomography.

Ultra-selective carbon nanotubes for photoacoustic imaging of inflamed atherosclerotic plaques.

Disruption of vulnerable atherosclerotic plaques often leads to myocardial infarction and stroke, the leading causes of morbidity and mortality in the United States. A diagnostic method that detects high-risk atherosclerotic plaques at early stages could prevent these sequelae. The abundance of immune cells in the arterial wall, especially inflammatory Ly-6C monocytes and foamy macrophages, is indicative of plaque‎ inflammation, and may be associated with plaque vulnerability.

Potential of Gold Nanoparticles for Noninvasive Imaging and Therapy for Vascular Inflammation.

Purpose: Macrophages contribute to the progression of vascular inflammation, making them useful targets for imaging and treatment of vascular diseases. Gold nanoparticles (GNPs) are useful as computed tomography (CT) contrast agents and light absorbers in photothermal therapy. In this study, we aimed to assess the viability of macrophages incubated with GNPs after near-infrared (NIR) laser light exposure and to evaluate the utility of intravenously injected GNPs for in vivo imaging of vascular inflammation in mice using micro-CT.

Detection of Carotid Artery Stenosis with Intraplaque Hemorrhage and Neovascularization Using a Scanning Interferometer.

Carotid artery stenosis (CAS) is a major cause of stroke or transient ischemic attack (TIA, mini-stroke) in the United States. Carotid endarterectomy (CEA), a surgical procedure, is used to treat CAS. According to the American Heart Association, 1 out of 5 patients underwent CEA inappropriately, which was most commonly due to apparent overestimation of stenosis severity, and half had uncertain indicators.

study of iron oxide-calcium phosphate composite nanoparticles for delivery to atherosclerosis.

Atherosclerosis is a macrophage-related inflammatory disease that remains a leading cause of death worldwide. Magnetic iron oxide (IO) nanocrystals are clinically used as magnetic resonance imaging contrast agents and their application as a detection agent for macrophages in arterial lesions has been studied extensively. We recently fabricated heparin-modified calcium phosphate (CaP) nanoparticles loaded with a large number of IO nanocrystals via coprecipitation from a supersaturated CaP solution supplemented with heparin and ferucarbotran (IO nanocrystals coated with carboxydextran).

Proteomic identification and validation of novel interactions of the putative tumor suppressor PRELP with membrane proteins including IGFI-R and p75NTR.

Proline and arginine-rich end leucine-rich repeat protein (PRELP) is a member of the small leucine-rich repeat proteoglycans (SLRPs) family. Levels of PRELP mRNA are downregulated in many types of cancer, and PRELP has been reported to have suppressive effects on tumor cell growth, although the molecular mechanism has yet to be fully elucidated. Given that other SLRPs regulate signaling pathways through interactions with various membrane proteins, we reasoned that PRELP likely interacts with membrane proteins to maintain cellular homeostasis.

Fabrication of gold-calcium phosphate composite nanoparticles through coprecipitation mediated by amino-terminated polyethylene glycol.

Calcium phosphate (CaP) nanoparticles immobilizing gold (Au) nanocrystals (Au-CaP composite nanoparticles) would be useful in diagnoses and/or treatments with Au nanocrystals. In this study, we achieved the rapid one-pot fabrication of such nanoparticles via coprecipitation in labile supersaturated CaP solutions by using appropriate Au sources, namely, Au nanocrystals coated with amino-terminated polyethylene glycol (PEG). In this process, amino groups at the PEG terminal played a crucial role in the coprecipitation with CaP through affinity interactions, and thus in the formation of Au-CaP composite nanoparticles; however, the molecular weight of the PEG chain was not a controlling factor in the coprecipitation.

Highly sensitive HPLC analysis and biophysical characterization of N-glycans of IgG-Fc domain in comparison between CHO and 293 cells using FcγRIIIa ligand.

Quality control of monoclonal antibodies is challenging due in part to the diversity of post-translational modifications present. The regulation of the N-glycans of IgG-Fc domain is one of the key factors to maintain the safety and efficacy of antibody drugs. The FcγRIIIa affinity column is an attractive tool for the precise analysis of the N-glycans in IgG-Fc domain.

Noninvasive Mapping of Premature Ventricular Contractions by Merging Magnetocardiography and Computed Tomography.

Objectives: This study aimed to develop a novel premature ventricular contraction (PVC) mapping method to predict PVC origins in whole ventricles by merging a magnetocardiography (MCG) image with a cardiac computed tomography (CT) image.

Background: MCG can noninvasively discriminate PVCs originating from the aortic sinus cusp from those originating from the right ventricular outflow tract.

Methods: This study was composed of 22 candidates referred for catheter ablation of idiopathic PVCs.

Facile one-pot fabrication of calcium phosphate-based composite nanoparticles as delivery and MRI contrast agents for macrophages.

We developed a facile one-pot fabrication process for magnetic iron oxide-calcium phosphate (IO-CaP) composite nanoparticles via coprecipitation in labile supersaturated CaP solutions containing IO nanocrystals. All the source solutions used were clinically approved for injection, including water and magnetic IO nanocrystals (ferucarbotran, used as a negative magnetic resonance imaging (MRI) contrast agent). This ensured that the resulting nanoparticles were pathogen- and endotoxin-free.

Myocardial perfusion reserve quantified by cardiac magnetic resonance imaging is associated with late gadolinium enhancement in hypertrophic cardiomyopathy.

Late gadolinium enhancement (LGE) with cardiac magnetic resonance (CMR) imaging has demonstrated the capability of stratifying hypertrophic cardiomyopathy (HCM). Stress perfusion test of CMR can quantify myocardial perfusion reserve (MPR), but its clinical role is not determined. The purpose of this study was to investigate the relationship between MPR and LGE in patients with HCM.

RGD targeting of human ferritin iron oxide nanoparticles enhances in vivo MRI of vascular inflammation and angiogenesis in experimental carotid disease and abdominal aortic aneurysm.

Purpose: To evaluate Arg-Gly-Asp (RGD)-conjugated human ferritin (HFn) iron oxide nanoparticles for in vivo magnetic resonance imaging (MRI) of vascular inflammation and angiogenesis in experimental carotid disease and abdominal aortic aneurysm (AAA).

Materials And Methods: HFn was genetically engineered to express the RGD peptide and Fe O nanoparticles were chemically synthesized inside the engineered HFn (RGD-HFn). Macrophage-rich left carotid lesions were induced by ligation in FVB mice made hyperlipidemic and diabetic (n = 14), with the contralateral right carotid serving as control.

Cathepsin Activity-Based Probes and Inhibitor for Preclinical Atherosclerosis Imaging and Macrophage Depletion.

Background And Purpose: Cardiovascular disease is the leading cause of death worldwide, mainly due to an increasing prevalence of atherosclerosis characterized by inflammatory plaques. Plaques with high levels of macrophage infiltration are considered "vulnerable" while those that do not have significant inflammation are considered stable; cathepsin protease activity is highly elevated in macrophages of vulnerable plaques and contributes to plaque instability. Establishing novel tools for non-invasive molecular imaging of macrophages in plaques could aid in preclinical studies and evaluation of therapeutics.

Multimodality Molecular Imaging of Cardiac Cell Transplantation: Part II. In Vivo Imaging of Bone Marrow Stromal Cells in Swine with PET/CT and MR Imaging.

Purpose To quantitatively determine the limit of detection of marrow stromal cells (MSC) after cardiac cell therapy (CCT) in swine by using clinical positron emission tomography (PET) reporter gene imaging and magnetic resonance (MR) imaging with cell prelabeling. Materials and Methods Animal studies were approved by the institutional administrative panel on laboratory animal care. Seven swine received 23 intracardiac cell injections that contained control MSC and cell mixtures of MSC expressing a multimodality triple fusion (TF) reporter gene (MSC-TF) and bearing superparamagnetic iron oxide nanoparticles (NP) (MSC-TF-NP) or NP alone.

Multimodality Molecular Imaging of Cardiac Cell Transplantation: Part I. Reporter Gene Design, Characterization, and Optical in Vivo Imaging of Bone Marrow Stromal Cells after Myocardial Infarction.

Purpose To use multimodality reporter-gene imaging to assess the serial survival of marrow stromal cells (MSC) after therapy for myocardial infarction (MI) and to determine if the requisite preclinical imaging end point was met prior to a follow-up large-animal MSC imaging study. Materials and Methods Animal studies were approved by the Institutional Administrative Panel on Laboratory Animal Care. Mice (n = 19) that had experienced MI were injected with bone marrow-derived MSC that expressed a multimodality triple fusion (TF) reporter gene.