CD137 Signal Mediates Cardiac Ischemia-Reperfusion Injury by Regulating the Necrosis of Cardiomyocytes.

The injury of cardiomyocytes after ischemia-reperfusion is the main reason of cardiac dysfunction. Necrosis is one of the methods of programmed cell death and cardiomyocyte necrosis occurs in the process of reperfusion. The activation of CD137 signal is involved in various diseases.

Antithrombotic Therapy With Ticagrelor in Atrial Fibrillation Subjects After Percutaneous Coronary Intervention.

Warfarin, along with aspirin and clopidogrel, has long been recommended for patients with atrial fibrillation (AF) who are undergoing percutaneous coronary intervention with a drug-eluting stent (PCI-DES). However, this triple therapy has been known to increase the risk of bleeding complications. Meanwhile, there is no evidence from prospective trials on the use of ticagrelor in a dual therapy.

OxLDL/β2GPI/anti‑β2GPI Ab complex induces inflammatory activation via the TLR4/NF‑κB pathway in HUVECs.

Patients with antiphospholipid syndrome have been identified to have higher incidence rates of atherosclerosis (AS) due to the elevated levels of anti‑β2‑glycoprotein I (β2GPI) antibody (Ab). Our previous studies revealed that the anti‑β2GPI Ab formed a stable oxidized low‑density lipoprotein (oxLDL)/β2GPI/anti‑β2GPI Ab complex, which accelerated AS development by promoting the accumulation of lipids in macrophages and vascular smooth muscle cell. However, the effects of the complex on endothelial cells, which drive the initiation and development of AS, remain unknown.

Activating CD137 Signaling Promotes Sprouting Angiogenesis via Increased VEGFA Secretion and the VEGFR2/Akt/eNOS Pathway.

Combination of antiangiogenesis and immunotherapy may be an effective strategy for treatment of solid tumors. Our previous work reported that activation of CD137 signaling promotes intraplaque angiogenesis. A number of studies have demonstrated that vascular endothelial growth factor receptor 2 (VEGFR2) is a key target for angiogenesis.

Advanced Glycation End Products Induce Vascular Smooth Muscle Cell-Derived Foam Cell Formation and Transdifferentiate to a Macrophage-Like State.

Background: Advanced glycation end products play an important role in diabetic atherosclerosis. The effects of advanced glycation end products (AGEs) on vascular smooth muscle cell- (VSMC-) derived foam cell formation and phenotypic transformation are unknown.

Methods: Serological and histological samples were obtained from diabetic amputation patients and accident amputation patients from the Affiliated Hospital of Jiangsu University.

Extracellular cyclophilin A induces cardiac hypertrophy via the ERK/p47phox pathway.

Excessive reactive oxygen species (ROS) are a critical driver of cardiac hypertrophy developing into heart failure. Cyclophilin A (CyPA), a member of the cyclophilin family, has been highlighted as a main secreted ROS-induced factor. The mechanism by which extracellular CyPA interacts with cardiomyocytes is unclear.

Echocardiographic assessment of simultaneously measured left ventricular filling pressures in patients with normal left ventricular ejection fraction.

Background: Assessment of left ventricular (LV) diastolic function is part of routine echocardiographic examinations. Accuracy of the 2016 ASE/EACVI algorithm to detect LV diastolic dysfunction in patients with a normal LV ejection fraction (LVEF) has been examined but simultaneous measurements of LV pressures and echocardiographic parameters of diastolic function are sparse.

Methods: The accuracy of multiple echo parameters of diastolic dynamics and the 2016 guidelines were assessed by simultaneous transthoracic echocardiography and LV pressure recordings in 120 patients (derivation cohort) and 60 patients (validation cohort) with suspected coronary artery disease and normal LVEF.

Serial assessment of focal myocardial function after percutaneous coronary intervention for ST-elevation myocardial infarction: Value of layer-specific speckle tracking echocardiography.

Background: Ischemia-reperfusion injury (IRI) frequently follows successful PCI for STEMI and is recognized by multiple modalities. Multilayer speckle tracking echocardiography (STE) has the potential of detecting myocardial dysfunction in different myocardial layers. Our objective was to describe the changes in layer-specific myocardial function over the 24 hours after successful PCI for ST-elevation myocardial infarction (STEMI).

Use of Inflammatory Biomarkers and Real-Time Cardiac Catheterisation to Evaluate the Left Ventricular Diastolic Function in Patients With Diastolic Heart Failure.

Background: Interleukin (IL)-17 and its related cytokines have been shown to be involved in myocardial fibrosis and irreversible ventricular remodelling, which have predictive values in the development of left ventricular diastolic dysfunction (LVDD). This study aimed to assess the correlation between IL-17 and LVDD, and investigate the prognostic value of IL-17 among patients with normal left ventricular ejection fraction (LVEF).

Methods: A total of 120 patients with normal LVEF underwent left ventricular (LV) catheterisation for LV end-diastolic pressure (LVEDP) measurement and routine echocardiography.

Role of Macrophages in the Progression and Regression of Vascular Calcification.

Vascular calcification is an abnormal cell-mediated process in which bone-specific hydroxyapatite crystals are actively deposited on the blood vessel wall and is a significant pathological basis for the increased incidence and mortality of adverse cardiovascular events. Macrophages play an important regulatory role in the occurrence, development, and regression of vascular calcification. After the tissue microenvironment changes, macrophages subsequently change their polarity and phenotype or secrete functional substances as an adaptive response.

Macrophage galectin-3 enhances intimal translocation of vascular calcification in diabetes mellitus.

The clinical risks and prognosis of diabetic vascular intimal calcification (VIC) and medial calcification (VMC) are different. This study aims to investigate the mechanism of VIC/VMC translocation. Anterior tibial arteries were collected from patients with diabetic foot amputation.

N-Carboxymethyl-Lysine Negatively Regulates Foam Cell Migration via the Vav1/Rac1 Pathway.

Background: Macrophage-derived foam cells play a central role in atherosclerosis, and their ultimate fate includes apoptosis, promotion of vascular inflammation, or migration to other tissues. N-Carboxymethyl-lysine (CML), the key active component of advanced glycation end products, induced foam cell formation and apoptosis. Previous studies have shown that the Vav1/Rac1 pathway affects the macrophage cytoskeleton and cell migration, but its role in the pathogenesis of diabetic atherosclerosis is unknown.

Exosome derived from CD137-modified endothelial cells regulates the Th17 responses in atherosclerosis.

The role of exosomes derived from endothelial cells (ECs) in the progression of atherosclerosis (AS) and inflammation remains largely unexplored. We aimed to investigate whether exosome derived from CD137-modified ECs (CD137-Exo) played a major role in AS and to elucidate the potential mechanism underlying the inflammatory effect. Exosomes derived from mouse brain microvascular ECs treated with agonist anti-CD137 antibody were used to explore the effect of CD137 signalling in AS and inflammation in vitro and vivo.

A Case of Transcatheter Aortic Valve Replacement for the Treatment of Severe Aortic Stenosis with Multiple Organ Dysfunction.

A 77-year-old woman with extremely high risk of mortality due to severe aortic stenosis (AS) and multiple organ failure was admitted to the affiliated hospital of Jiangsu University. She did not receive regular treatment since being diagnosed with AS 17 months previously. Frequent breakout of acute left heart failure after admission, with a low ostium of the left coronary artery showed by computed tomography, the patient underwent transcatheter aortic valve replacement (TAVR).

F-FDG uptake velocity but not uptake level is associated with progression of carotid plaque.

Objectives: The objective of this study was to evaluate whether baseline F-fluorodeoxyglucose (FDG) uptake is associated with carotid plaque progression.

Methods: A total of 156 subjects with carotid plaque were enrolled and underwent carotid magnetic resonance imaging (MRI) (at baseline and the 12-month follow-up) and positron emission tomography-computed tomography (PET-CT) (baseline). Carotid plaque progression was evaluated by two indices (the incidence of plaque progression and percentage of plaque increase) with three-dimensional (3D) imaging, while the F-FDG uptake was evaluated by the F-FDG uptake levels and F-FDG uptake velocity.

Role of CyPA in cardiac hypertrophy and remodeling.

Pathological cardiac hypertrophy is a complex process and eventually develops into heart failure, in which the heart responds to various intrinsic or external stress, involving increased interstitial fibrosis, cell death and cardiac dysfunction. Studies have shown that oxidative stress is an important mechanism for this maladaptation. Cyclophilin A (CyPA) is a member of the cyclophilin (CyPs) family.

Activation of CD137 signaling promotes neointimal formation by attenuating TET2 and transferrring from endothelial cell-derived exosomes to vascular smooth muscle cells.

Activated endothelial cells (ECs) play an important role in the development of atherosclerosis (AS) because they form neointima resulting from abnormal vascular smooth muscle cell (VSMC) hyperplasia. TET2 was recently reported as a major regulator of the phenotypic switch of VSMCs, and it also protects ECs from noxious stimuli and represses inflammation in AS. The purpose of the present study is to determine whether activation of CD137 signaling can regulate the function of VSMCs by altering endothelial TET2 expression and to explore the potential mechanisms.

CD137-CD137L Signaling Affects Angiogenesis by Mediating Phenotypic Conversion of Macrophages.

Background: Angiogenesis in atherosclerotic plaque is an important factor causing plaque hemorrhage, vulnerability, and rupture, and different phenotypes of macrophages have different effects on angiogenesis. Our previous study has demonstrated CD137-CD137L signaling, a pair of inflammatory costimulatory molecules, can promote angiogenesis in atherosclerotic plaque. Therefore, we aimed to investigate whether this signaling could affect angiogenesis by regulating phenotypic transition of macrophages.

Role of Matrix Vesicles in Bone-Vascular Cross-Talk.

Matrix mineralization can be divided into physiological mineralization and pathological mineralization. There is a consensus among existing studies that matrix vesicles (MVs) are the starting sites of bone mineralization, and each component of MVs serves a certain function in mineralization. In addition, ectopic MVs pathologically promote undesired calcification, the primary focus of which is the promotion of vascular calcification.

Increased ASL-CBF in the right amygdala predicts the first onset of depression in healthy young first-degree relatives of patients with major depression.

Healthy first-degree relatives of patients with major depression are at an elevated risk of developing depression, and regional cerebral blood flow (CBF) alterations are observed in patients with depression. Therefore, in a 33-month follow-up study, we used arterial spin labeling-magnetic resonance imaging (ASL-MRI) to investigate quantitative CBF before and after the diagnosis of depression in healthy young adults with and without first-degree relatives with major depression (FH + and FH-, respectively). In cross-sectional and longitudinal CBF comparisons, CBF in the right amygdala was increased or decreased.

Mechanisms of Matrix Vesicles Mediating Calcification Transition in Diabetic Plaque.

Vascular calcification is a key character of advanced plaque in diabetic atherosclerosis. Microcalcification induces plaque rupture, whereas macrocalcification contributes to plaque stability. However, there is still no clear explanation for the formation and transition of these two types of calcification.

Cyclophilin A Protects Cardiomyocytes against Hypoxia/Reoxygenation-Induced Apoptosis via the AKT/Nox2 Pathway.

Hypoxia/reoxygenation (H/R) accelerates the process of cardiomyocyte apoptosis during ischemia-reperfusion. Excessive reactive oxygen species (ROS) are a critical driver of oxidative stress injury. Cyclophilin A (CyPA) is a major ROS-induced factor in atherosclerosis.

Nε-carboxymethyl-lysine-induced PI3K/Akt signaling inhibition promotes foam cell apoptosis and atherosclerosis progression.

Advanced glycation end products (AGEs) are closely associated with diabetic macrovascular complications. The present study aimed to investigate the effects of Nε-Carboxymethyl-Lysine (the key active component of AGEs) in diabetic atherosclerosis on foam cell apoptosis and to explore the underlying mechanisms. Tissue sections were collected from 12 Type 2 diabetic patients and 4 control patients who underwent amputation surgery following a car accident.