Endothelial damage inhibitor preserves the integrity of venous endothelial cells from patients undergoing coronary bypass surgery.

Objectives: Despite the success of coronary artery bypass graft (CABG) surgery using autologous saphenous vein grafts (SVGs), nearly 50% of patients experience vein graft disease within 10 years of surgery. One contributing factor to early vein graft disease is endothelial damage during short-term storage of SVGs in inappropriate solutions. Our aim was to evaluate the effects of a novel endothelial damage inhibitor (EDI) on SVGs from patients undergoing elective CABG surgery and on venous endothelial cells (VECs) derived from these SVGs.

A clinical study to evaluate the safe and effective use of a new, single use stethoscope cover to enable reduction in pathogen transmission during auscultation.

Objectives: Stethoscopes carry a significant risk for pathogen transmission. Here, the safe use and performance of a new, non-sterile, single-use stethoscope cover (SC), that is impermeable for pathogens, was investigated by different healthcare professionals (HCPs) in the postoperative care setting of an intensive care unit (ICU).

Methods: Fifty-four patients underwent routine auscultations with the use of the SC (Stethoglove, Stethoglove GmbH, Hamburg, Germany).

Anisotropic topographies restore endothelial monolayer integrity and promote the proliferation of senescent endothelial cells.

Thrombogenicity remains a major issue in cardiovascular implants (CVIs). Complete surficial coverage of CVIs by a monolayer of endothelial cells (ECs) prior to implantation represents a promising strategy but is hampered by the overall logistical complexity and the high number of cells required. Consequently, extensive cell expansion is necessary, which may eventually lead to replicative senescence.

MiRNA Profiles of Extracellular Vesicles Secreted by Mesenchymal Stromal Cells-Can They Predict Potential Off-Target Effects?

The cardioprotective properties of extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) are currently being investigated in preclinical studies. Although microRNAs (miRNAs) encapsulated in EVs have been identified as one component responsible for the cardioprotective effect of MSCs, their potential off-target effects have not been sufficiently characterized. In the present study, we aimed to investigate the miRNA profile of EVs isolated from MSCs that were derived from cord blood (CB) and adipose tissue (AT).

MicroRNA Mediated Cardioprotection - Is There a Path to Clinical Translation?

In the past 20 years, there have been several approaches to achieve cardioprotection or cardiac regeneration using a vast variety of cell therapies and remote ischemic pre-conditioning (RIPC). To date, substantial proof that either cell therapy or RIPC has the potential for clinically relevant cardiac repair or regeneration of cardiac tissue is still pending. Preclinical trials indicate that the secretome of cells (during RIPC) as well as of transplanted cells may exhibit cardioprotective properties in the acute setting of cardiac injury.

Serelaxin Improves Regional Myocardial Function in Experimental Heart Failure: An In Vivo Cardiac Magnetic Resonance Study.

Background Animal studies demonstrated that serelaxin lessens fibrosis in heart failure. This study assessed its effect on myocardial deformation using cardiac magnetic resonance and elucidated its relationship to gene regulation and histology in a mouse heart failure model. Methods and Results C57BL/6J mice were subjected to SHAM (n=4) or transverse aortic constriction (TAC).

Cardiovascular magnetic resonance feature tracking in small animals - a preliminary study on reproducibility and sample size calculation.

Background: Cardiovascular magnetic resonance feature tracking (CMR-FT) is a novel tissue tracking technique developed for noninvasive assessment of myocardial motion and deformation. This preliminary study aimed to evaluate the observer's reproducibility of CMR-FT in a small animal (mouse) model and define sample size calculation for future trials.

Methods: Six C57BL/6 J mice were selected from the ongoing experimental mouse model onsite and underwent CMR with a 3 Tesla small animal MRI scanner.

PCSK9 regulates the chemokine receptor CCR2 on monocytes.

Unlabelled: Monocyte migration is a key element in atherosclerosis. LDL-C facilitates monocyte migration via induction of CCR2. PCSK9 regulates cell surface expression of the LDL-R and is expressed in vascular smooth muscle cells (VSMCs).

Inhibition of Src homology 2 domain-containing phosphatase 1 increases insulin sensitivity in high-fat diet-induced insulin-resistant mice.

Insulin resistance plays a crucial role in the development of type 2 diabetes. Insulin receptor signalling is antagonized and tightly controlled by protein tyrosine phosphatases (PTPs). However, the precise role of the PTP src homology 2 domain-containing phosphatase 1 (SHP-1) in insulin resistance has not been explored.

Proprotein convertase subtilisin/kexin type 3 promotes adipose tissue-driven macrophage chemotaxis and is increased in obesity.

Background: Matrix metalloproteinase (MMP)-dependent extracellular matrix (ECM) remodeling is a key feature in cardiometabolic syndrome-associated adipogenesis and atherosclerosis. Activation of membrane-tethered (MT) 1-MMP depends on furin (PCSK3). However, the regulation and function of the natural furin-inhibitor serpinB8 and thus furin/MT1-MMP-activity in obesity-related tissue inflammation/remodeling is unknown.

Targeting density-enhanced phosphatase-1 (DEP-1) with antisense oligonucleotides improves the metabolic phenotype in high-fat diet-fed mice.

Background: Insulin signaling is tightly controlled by tyrosine dephosphorylation of the insulin receptor through protein-tyrosine-phosphatases (PTPs). DEP-1 is a PTP dephosphorylating tyrosine residues in a variety of receptor tyrosine kinases. Here, we analyzed whether DEP-1 activity is differentially regulated in liver, skeletal muscle and adipose tissue under high-fat diet (HFD), examined the role of DEP-1 in insulin resistance in vivo, and its function in insulin signaling.

Soluble P-selectin level correlates with acetylsalicylic acid but not with clopidogrel response in patients with stable coronary artery disease after a percutaneous coronary intervention.

Background: Impaired response to dual antiplatelet therapy is associated with worse cardiovascular outcome. Besides antiplatelet effects, there is evidence that both clopidogrel and acetylsalicylic acid (ASA) have anti-inflammatory properties. However, little is known about the relationship between platelet function and inflammation under dual antiplatelet therapy in patients with stable coronary artery disease.

Proprotein convertase furin enhances survival and migration of vascular smooth muscle cells via processing of pro-nerve growth factor.

Maturation of nerve growth factor (NGF) in neuronal cells requires endoproteolytic processing of the precursor protein proNGF to β-NGF by the proprotein convertase furin. Pro- and β-NGF elicit opposite biological functions by differential neurotrophin-receptor binding, leading to apoptosis via sortilin or survival via neurotrophic tyrosine kinase receptor type-1 (TrkA), respectively. The present study was done to investigate the impact of furin-dependent proNGF processing on vascular smooth muscle cell (VSMC) function.

The (pro)renin receptor ((P)RR) can act as a repressor of Wnt signalling.

The (pro)renin receptor ((P)RR) and Wnt signalling are both involved in different diseases ranging from cardiac and renal end-organ damage to cancer. (P)RR function involves signalling via the transcription factor promyelocytic leukemia zinc finger protein (PLZF) as well as the furin-mediated generation of vacuolar proton-translocating ATPase (V-ATPase)-associated and soluble (P)RR isoforms. Recently, the (P)RR was described as adaptor protein of Wnt (co)receptors.

Granulocyte colony-stimulating factor improves cerebrovascular reserve capacity by enhancing collateral growth in the circle of Willis.

Background And Purpose: Restoration of cerebrovascular reserve capacity (CVRC) depends on the recruitment and positive outward remodeling of preexistent collaterals (arteriogenesis). With this study, we provide functional evidence that granulocyte colony-stimulating factor (G-CSF) augments therapeutic arteriogenesis in two animal models of cerebral hypoperfusion. We identified an effective dosing regimen that improved CVRC and stimulated collateral growth, thereby improving the outcome after experimentally induced stroke.

Acetylsalicylic acid, but not clopidogrel, inhibits therapeutically induced cerebral arteriogenesis in the hypoperfused rat brain.

This study investigated the effects of acetylsalicylic acid (ASA) and clopidogrel, standardly used in the secondary prevention of vascular occlusions, on cerebral arteriogenesis in vivo and in vitro. Cerebral hypoperfusion was induced by three-vessel occlusion (3-VO) in rats, which subsequently received vehicle, ASA (6.34 mg/kg), or clopidogrel (10 mg/kg).

CD40/CD40L interaction induces E-selectin dependent leukocyte adhesion to human endothelial cells and inhibits endothelial cell migration.

Background: CD40 is a receptor expressed on a wide range of cells such as leukocytes and endothelial cells (EC). As a member of the tumor necrosis factor (TNF) superfamily the activation of CD40 by CD40-ligand (CD40L) plays a crucial role for the development and progression of a variety of inflammatory processes including atherosclerosis. The aim of the present study was to investigate the effect of CD40/CD40L interaction on leukocyte adhesion to the endothelium and on endothelial cell migration.

IGF-1 increases macrophage motility via PKC/p38-dependent alphavbeta3-integrin inside-out signaling.

Unlabelled: Macrophage migration is a key aspect in the initiation and progression of atherosclerosis. Insulin-like growth factor (IGF)-1 is highly expressed in macrophages in human atheroma. Its function in macrophage motility, however, remains to be elucidated.

Integrin cleavage regulates bidirectional signalling in vascular smooth muscle cells.

Integrins link the cytoskeleton to the extracellular matrix, providing outside-in/inside-out signalling essential for vascular smooth muscle cell (VSMC) migration in atherosclerosis. The integrin av subunit is synthesised from its precursor via furin-dependent endoproteolytic cleavage. Furin is a proprotein convertase (PC) highly expressed in VSMCs and in human atherosclerotic lesions.

Integrin cleavage facilitates cell surface-associated proteolysis required for vascular smooth muscle cell invasion.

Vascular smooth muscle cell (VSMC) invasion is a key element in atherogenesis and restenosis, requiring integrins for adhesion/de-adhesion as well as matrix metalloproteinases (MMPs) for focalized proteolysis. Among the MMP family, pro-MMP-2 is unique in its activation, depending on the formation of a multiprotein complex with MT1-MMP/TIMP-2 at the cell surface, in which integrin alphavbeta3 participates. Integrin alphav and MT1-MMP are synthesized from precursors via furin-dependent cleavage of their pro-peptide.

Insulin facilitates monocyte migration: a possible link to tissue inflammation in insulin-resistance.

Mononuclear cells (MNCs) are the primary cell type involved in the pro-inflammatory state of obesity-linked insulin-resistance, and atherosclerosis. Increased serum levels of MMP-9 are reported in insulin-resistant type 2 diabetic patients. Here we demonstrate insulin facilitating human monocytic THP-1 cell chemotaxis via prolonged Erk1/2-dependent induction of MMP-9.

ED-B fibronectin (ED-B) can be targeted using a novel single chain antibody conjugate and is associated with macrophage accumulation in atherosclerotic lesions.

It has been shown that ED-B fibronectin (ED-B) is a potential target for plaque imaging. The aim of this study was to test a novel modified single chain anti-ED-B antibody (scFv) conjugated for near infrared fluorescence imaging (NIRF) with tetrasulfonated carbocyanine-maleimide (TSC-scFv) and to examine the association of ED-B with the presence of macrophages in a murine model of atherosclerosis. Expression of ED-B was observed in plaque areas in apolipoprotein E-deficient (apoE(-/-)) mice which increased with age and plaque load.

Insulin augments matrix metalloproteinase-9 expression in monocytes.

Objective: Insulin resistance and hyperinsulinemia are major causes of cardiovascular morbidity and mortality. Matrix metalloproteinases (MMPs), highly expressed in activated mononuclear cells in vulnerable atherosclerotic lesions, are the main proteolytic enzymes controlling plaque stability. The aim of this study was to investigate the regulation of monocyte MMP-9 by insulin.

Furin-like proprotein convertases are central regulators of the membrane type matrix metalloproteinase-pro-matrix metalloproteinase-2 proteolytic cascade in atherosclerosis.

Background: Accumulation of macrophages and their in situ expression of matrix metalloproteinases (MMPs) are important determinants of plaque stability. Activation of membrane-bound MT1-MMP, the major activator of pro-MMP-2, requires intracellular endoproteolytic cleavage of its precursor protein. This type of activation typically requires suitable furin-like proprotein convertases (PCs), specifically furin and PC5.