Subpulmonary ventricular function and inflammation are related to clinical heart failure in patients with a systemic right ventricle.

Background: Timely diagnosis of heart failure (HF) in patients with a systemic right ventricle (sRV) is difficult but important since clinical deterioration is fast once HF develops. We aimed to compare echocardiography and biomarker profile between sRV patients with and without HF and patients with a systemic left ventricle diagnosed with HF (sLV-HF).

Methods And Results: Eighty-seven sRV patients and 30 sLV-HF patients underwent echocardiographic evaluation and blood sampling.

NET burden in left atrial blood is associated with biomarkers of thrombosis and cardiac injury in patients with enlarged left atria.

Background: Emerging data suggest an association between left atrial (LA) enlargement, thrombus formation, and ischemic stroke. However, it is unknown what may mediate such clot formation in LA dysfunction. Neutrophils promote large vessel occlusion and microthrombosis via neutrophil extracellular trap (NET) release, thus lying at the interface of inflammation, thrombosis, and fibrosis.

Involvement of peptidylarginine deiminase 4 in eosinophil extracellular trap formation and contribution to citrullinated histone signal in thrombi.

Background: Extracellular traps formed by neutrophils (NETs) and eosinophils (EETs) have been described in coronary thrombi, contributing to thrombus stability. A key mechanism during NET formation is histone modification by the enzyme PAD4. Citrullinated histones, the product of PAD4 activity, are often attributed to neutrophils.

Neutrophil peptidylarginine deiminase 4 is essential for detrimental age-related cardiac remodelling and dysfunction in mice.

Mice fully deficient in peptidylarginine deiminase 4 (PAD4) enzyme have preserved cardiac function and reduced collagen deposition during ageing. The cellular source of PAD4 is hypothesized to be neutrophils, likely due to PAD4's involvement in neutrophil extracellular trap release. We investigated haematopoietic PAD4 impact on myocardial remodelling and systemic inflammation in cardiac ageing by generating mice with deletion in circulating neutrophils under the MRP8 promoter (Ne-PAD4), and ageing them for 2 years together with littermate controls (PAD4).

Peripheral serotonin lacks effects on endothelial adhesion molecule expression in acute inflammation.

Background: Peripheral, non-neuronal serotonin promotes the recruitment of neutrophils to sites of acute inflammation and tissue damage. Direct effects of serotonin on neutrophil function were shown to be involved. However, the influence of serotonin on the endothelial counterpart is unknown.

Monocyte Dysfunction Detected by the Designed Ankyrin Repeat Protein F7 Predicts Mortality in Patients Receiving Veno-Arterial Extracorporeal Membrane Oxygenation.

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is used for critically ill patients requiring hemodynamic support but has been shown to induce an inflammatory response syndrome potentially leading to severe complications and poor outcome. Monocytes are comprised of different subsets and play a central role in the innate immune system. The small binding proteins, Designed Ankyrin Repeat Protein "F7" and single chain variable fragment "MAN-1," specifically detect the activated conformation of the leukocyte integrin Mac-1 enabling the highly sensitive detection of monocyte activation status.

Inflammation in acute coronary syndrome: Expression of TLR2 mRNA is increased in platelets of patients with ACS.

Background: Platelets are key components in atherogenesis and determine the course of its clinical sequelae acute coronary syndrome (ACS). Components of the innate immune system-the superfamily of TLR receptors-are present in platelets and represent a link between atherothrombosis and inflammation. We hypothesize that alteration in platelet TLR mRNA expression is a result of inflammation driving coronary atherosclerosis and may represent an alternative platelet activation pathway in ACS.

Diagnostic value of lead aVR in electrocardiography for identifying acute coronary lesions in patients with out-of-hospital cardiac arrest.

Aim: There is no simple clinical tool that reliably indicates the presence of acute coronary lesions in out-of-hospital cardiac arrest (OHCA) patients without typical ST-segment elevations. ST-segment elevation in electrocardiographic lead aVR suggests global subendocardial ischemia. This study aimed to evaluate the diagnostic value of lead aVR for identifying acute coronary lesions following resuscitation from OHCA.

Platelet Serotonin Aggravates Myocardial Ischemia/Reperfusion Injury via Neutrophil Degranulation.

Background: Platelets store large amounts of serotonin that they release during thrombus formation or acute inflammation. This facilitates hemostasis and modulates the inflammatory response.

Methods: Infarct size, heart function, and inflammatory cell composition were analyzed in mouse models of myocardial reperfusion injury with genetic and pharmacological depletion of platelet serotonin.

Recombinant Human ADAMTS13 Treatment Improves Myocardial Remodeling and Functionality After Pressure Overload Injury in Mice.

Background: A disintegrin-like metalloproteinase with thrombospondin motif type 1 member 13 (ADAMTS13), the von Willebrand factor-cleaving enzyme, decreases leukocyte and platelet recruitment and, thus, reduces thrombosis and inflammation. Recombinant human ADAMTS13 (rhADAMTS13) is a novel drug candidate for ischemia/reperfusion injury and has shown short-term benefits in mouse models of myocardial injury, but long-term outcome has not been investigated.

Methods And Results: We evaluated the impact of rhADAMTS13 on cardiac remodeling, scarring, and contractile function, under chronic left ventricular pressure overload.

Sirt3 deficiency does not affect venous thrombosis or NETosis despite mild elevation of intracellular ROS in platelets and neutrophils in mice.

Inflammation is a common denominator in chronic diseases of aging. Yet, how inflammation fuels these diseases remains unknown. Neutrophils are the primary leukocytes involved in the early phase of innate immunity and inflammation.

Peptidylarginine deiminase 4 promotes age-related organ fibrosis.

Aging promotes inflammation, a process contributing to fibrosis and decline in organ function. The release of neutrophil extracellular traps (NETs [NETosis]), orchestrated by peptidylarginine deiminase 4 (PAD4), damages organs in acute inflammatory models. We determined that NETosis is more prevalent in aged mice and investigated the role of PAD4/NETs in age-related organ fibrosis.

Aortic Dissection Presenting as "Hysteria".

Background: Patients with medical conditions may present with psychiatric symptoms, which may lead to worse physical health care. Here we present the case of a patient with acute aortic dissection masked by psychiatric symptoms after a stressful event.

Case Report: A 29-year-old female medical student presented to the Emergency Department (ED) complaining about the feeling of "hysteria" after an argument with her boyfriend earlier the same day.

Dual-contrast molecular imaging allows noninvasive characterization of myocardial ischemia/reperfusion injury after coronary vessel occlusion in mice by magnetic resonance imaging.

Background: Inflammation and myocardial necrosis play important roles in ischemia/reperfusion injury after coronary artery occlusion and recanalization. The detection of inflammatory activity and the extent of myocardial necrosis itself are of great clinical and prognostic interest. We developed a dual, noninvasive imaging approach using molecular magnetic resonance imaging in an in vivo mouse model of myocardial ischemia and reperfusion.

Transglutaminase 2: a new player in bronchopulmonary dysplasia?

Aberrant remodelling of the extracellular matrix in the developing lung may underlie arrested alveolarisation associated with bronchopulmonary dysplasia (BPD). Transglutaminases are regulators of extracellular matrix remodelling. Therefore, the expression and activity of transglutaminases were assessed in lungs from human neonates with BPD and in a rodent model of BPD.

Acute fluoxetine treatment induces slow rolling of leukocytes on endothelium in mice.

Objective: Activated platelets release serotonin at sites of inflammation where it acts as inflammatory mediator and enhances recruitment of neutrophils. Chronic treatment with selective serotonin reuptake inhibitors (SSRI) depletes the serotonin storage pool in platelets, leading to reduced leukocyte recruitment in murine experiments. Here, we examined the direct and acute effects of SSRI on leukocyte recruitment in murine peritonitis.

Deregulation of the lysyl hydroxylase matrix cross-linking system in experimental and clinical bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a common and serious complication of premature birth, characterized by a pronounced arrest of alveolar development. The underlying pathophysiological mechanisms are poorly understood although perturbations to the maturation and remodeling of the extracellular matrix (ECM) are emerging as candidate disease pathomechanisms. In this study, the expression and regulation of three members of the lysyl hydroxylase family of ECM remodeling enzymes (Plod1, Plod2, and Plod3) in clinical BPD, as well as in an experimental animal model of BPD, were addressed.

A novel hollow and perforated flexible wire allows the safe and effective local application of thrombolytic therapy in a mouse model of deep vein thrombosis.

We tested the feasibility of local thrombolytic therapy via a novel hollow flexible and perforated wire in a mouse model of deep vein thrombosis. Inferior vena cava (IVC) thrombosis was induced by vessel wall exposure to ferric chloride after laparotomy in anesthetized C57Bl/6 mice. Thrombus formation was visualized by intravital microscopy of rhodamine-labeled platelets and leukocytes.