Rat Model of Right-Sided Cardiac Remodeling and Arrhythmia using Pulmonary Artery Banding.

Clinical conditions, including chronic obstructive pulmonary disease or pulmonary arterial hypertension (PAH), can lead to chronic right ventricle pressure overload and progressive right heart failure (RHF). RHF can be identified by right-sided cardiac hypertrophy and dilation associated with abnormal myocardial function affecting the RV and the right atrium (RA). We recently demonstrated that severe RHF is accompanied by an increased risk of atrial inflammation, atrial fibrosis, and atrial fibrillation (AF), the most common type of cardiac arrhythmia (CA).

Daily exposure to chlordecone, an organochlorine pesticide, increases cardiac fibrosis and atrial fibrillation vulnerability.

Context: Chlordecone (CLD) is a carcinogenic organochlorine pesticide. CLD was shown to disturb the activity of cardiac Na-K-ATPase and Ca-Mg-ATPase. Conditions affecting these transmembrane pumps are often associated with cardiac arrhythmias (CA).

ERK3 is involved in regulating cardiac fibroblast function.

ERK3/MAPK6 activates MAP kinase-activated protein kinase (MK)-5 in selected cell types. Male MK5 haplodeficient mice show reduced hypertrophy and attenuated increase in Col1a1 mRNA in response to increased cardiac afterload. In addition, MK5 deficiency impairs cardiac fibroblast function.

Atrial cardiomyocytes contribute to the inflammatory status associated with atrial fibrillation in right heart disease.

Aims: Right heart disease (RHD), characterized by right ventricular (RV) and atrial (RA) hypertrophy, and cardiomyocytes' (CM) dysfunctions have been described to be associated with the incidence of atrial fibrillation (AF). Right heart disease and AF have in common, an inflammatory status, but the mechanisms relating RHD, inflammation, and AF remain unclear. We hypothesized that right heart disease generates electrophysiological and morphological remodelling affecting the CM, leading to atrial inflammation and increased AF susceptibility.

A genetic mouse model of lean-NAFLD unveils sexual dimorphism in the liver-heart axis.

Lean patients with NAFLD may develop cardiac complications independently of pre-existent metabolic disruptions and comorbidities. To address the underlying mechanisms independent of the development of obesity, we used a murine model of hepatic mitochondrial deficiency. The liver-heart axis was studied as these mice develop microvesicular steatosis without obesity.

Low-Density Neutrophils Contribute to Subclinical Inflammation in Patients with Type 2 Diabetes.

Type 2 diabetes (T2D) is characterized by low-grade inflammation. Low-density neutrophils (LDNs) represent normally less than 2% of total neutrophils but increase in multiple pathologies, releasing inflammatory cytokines and neutrophil extracellular traps (NETs). We assessed the count and role of high-density neutrophils (HDNs), LDNs, and NET-related activities in patients with T2D.

The role of cellular senescence in profibrillatory atrial remodelling associated with cardiac pathology.

Aims: Cellular senescence is a stress-related or aging response believed to contribute to many cardiac conditions; however, its role in atrial fibrillation (AF) is unknown. Age is the single most important determinant of the risk of AF. The present study was designed to (i) evaluate AF susceptibility and senescence marker expression in rat models of aging and myocardial infarction (MI), (ii) study the effect of reducing senescent-cell burden with senolytic therapy on the atrial substrate in MI rats, and (iii) assess senescence markers in human atrial tissue as a function of age and the presence of AF.

An inflammation resolution-promoting intervention prevents atrial fibrillation caused by left ventricular dysfunction.

Aims: Recent studies suggest that bioactive mediators called resolvins promote an active resolution of inflammation. Inflammatory signalling is involved in the development of the substrate for atrial fibrillation (AF). The aim of this study is to evaluate the effects of resolvin-D1 on atrial arrhythmogenic remodelling resulting from left ventricular (LV) dysfunction induced by myocardial infarction (MI) in rats.

Chymase Inhibition Resolves and Prevents Deep Vein Thrombosis Without Increasing Bleeding Time in the Mouse Model.

Background Deep vein thrombosis (DVT) is the primary cause of pulmonary embolism and the third most life-threatening cardiovascular disease in North America. Post-DVT anticoagulants, such as warfarin, heparin, and direct oral anticoagulants, reduce the incidence of subsequent venous thrombi. However, all currently used anticoagulants affect bleeding time at various degrees, and there is therefore a need for improved therapeutic regimens in DVT.

Structural dysregulation of the pulmonary autograft was associated with a greater density of p16-vascular smooth muscle cells.

The present study tested the hypothesis that a senescent phenotype of vascular smooth muscle cells (VSMCs) may represent the seminal event linked to maladaptive pulmonary autograft remodeling of a small number of patients that underwent the Ross procedure. The diameter of the pulmonary autograft (47±4 mm) of three male patients was significantly greater compared to the pulmonary artery (26±1 mm) excised from bicuspid aortic valve (BAV) patients. The pulmonary autograft was associated with a neointimal region and the adjacent medial region was significantly thinner compared to the pulmonary artery of BAV patients.

Correlation between Neutrophil Extracellular Traps (NETs) Expression and Primary Graft Dysfunction Following Human Lung Transplantation.

Primary graft dysfunction (PGD) is characterized by alveolar epithelial and vascular endothelial damage and inflammation, lung edema and hypoxemia. Up to one-third of recipients develop the most severe form of PGD (Grade 3; PGD3). Animal studies suggest that neutrophils contribute to the inflammatory process through neutrophil extracellular traps (NETs) release (NETosis).

Neutrophils and Circulating Inflammatory Biomarkers in Diabetes Mellitus and Heart Failure With Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is characterized by low-grade chronic inflammation, which could be exacerbated by type 2 diabetes mellitus (DM). We hypothesized that neutrophils in patients with DM and patients with HFpEF with/without DM contribute to low-grade inflammation through the release of pro-inflammatory cytokines. Venous blood was withdrawn from patients with DM (n = 22), HFpEF (n = 15), HFpEF with DM (n = 13), and healthy controls (CTL) (n = 21).

Acute effect of passive heat exposure on markers of cardiometabolic function in adults with type 2 diabetes mellitus.

Heat therapy is a promising strategy to improve cardiometabolic health. This study evaluated the acute physiological responses to hot water immersion in adults with type 2 diabetes mellitus (T2DM). On separate days in randomized order, 13 adults with T2DM [8 males/5 females, 62 ± 12 yr, body mass index (BMI): 30.

Cholesterol absorption blocker ezetimibe prevents muscle wasting in severe dysferlin-deficient and mdx mice.

Background: Muscular dystrophy (MD) causes muscle wasting and is often lethal in patients due to a lack of proven therapies. In contrast, mouse models of MD are notoriously mild. We have previously shown severe human-like muscle pathology in mdx [Duchenne MD (DMD)] and dysferlin-deficient limb-girdle MD type 2B (LGMD2B) mice by inactivating the gene encoding for apolipoprotein E (ApoE), a lipid transporter synthesized by the liver, brain and adipocytes to regulate lipid and fat metabolism.

Neutrophils pro-inflammatory and anti-inflammatory cytokine release in patients with heart failure and reduced ejection fraction.

Aims: Heart failure with reduced ejection fraction (HFrEF) is characterized by sub-clinical inflammation. Changes in selected biomarkers of inflammation concomitant with the release of pro-inflammatory and anti-inflammatory cytokines by neutrophils have not been investigated in patients with HFrEF.

Methods And Results: Fifty-two patients, aged 68.

Angiopoietin 1 release from human neutrophils is independent from neutrophil extracellular traps (NETs).

Background: Neutrophils induce the synthesis and release of angiopoietin 1 (Ang1), a cytosolic growth factor involved in angiogenesis and capable of inducing several pro-inflammatory activities in neutrophils. Neutrophils also synthesize and release neutrophil extracellular traps (NETs), comprised from decondensed nuclear DNA filaments carrying proteins such as neutrophil elastase (NE), myeloperoxidase (MPO), proteinase 3 (PR3) and calprotectin (S100A8/S100A9), which together, contribute to the innate immune response against pathogens (e.g.

MK2-Deficient Mice Are Bradycardic and Display Delayed Hypertrophic Remodeling in Response to a Chronic Increase in Afterload.

Background Mitogen-activated protein kinase-activated protein kinase-2 (MK2) is a protein serine/threonine kinase activated by p38α/β. Herein, we examine the cardiac phenotype of pan MK2-null (MK2) mice. Methods and Results Survival curves for male MK2 and MK2 mice did not differ (Mantel-Cox test, =0.

Impact of diabetes on serum biomarkers in heart failure with preserved ejection fraction: insights from the TOPCAT trial.

Aims: Diabetes mellitus (DM) is common in heart failure with preserved ejection fraction (HFpEF). Patients with DM and heart failure with reduced ejection fraction have higher levels of cardiac, profibrotic, and proinflammatory biomarkers relative to non-diabetics. Limited data are available regarding the biomarker profiles of HFpEF patients with diabetes (DM) vs.

Colchicine reduces lung injury in experimental acute respiratory distress syndrome.

The acute respiratory distress syndrome (ARDS) is characterized by intense dysregulated inflammation leading to acute lung injury (ALI) and respiratory failure. There are no effective pharmacologic therapies for ARDS. Colchicine is a low-cost, widely available drug, effective in the treatment of inflammatory conditions.

Impact of Finnish sauna bathing on circulating markers of inflammation in healthy middle-aged and older adults: A crossover study.

Objectives: Finnish sauna bathing is associated with a reduced risk of adverse health outcomes. The acute physiological responses elicited by Finnish sauna bathing that could explain this association remain understudied. This study characterized the acute effect of Finnish sauna bathing on circulating markers of inflammation in healthy middle-aged and older adults.

Lymphocytopenia During Hospitalization for Acute Heart Failure and Its Relationship With Portal Congestion and Right Ventricular Function.

Background: Lymphocytopenia is associated with mortality in acute heart failure (AHF), and portal congestion has been suggested to play a role in leukocyte distribution. The associations between lymphocytopenia and ultrasound surrogates for portal congestion have never been studied. We aimed to characterize the determinants of lymphocytopenia, explore the associations between lymphocytopenia and portal congestion, and explore the relationships between lymphocytopenia and outcomes in AHF.

Acute Vascular Benefits of Finnish Sauna Bathing in Patients With Stable Coronary Artery Disease.

Background: Finnish sauna bathing habits are associated with a decreased risk of cardiovascular mortality. The physiologic adaptations mediating this association remain to be fully elucidated. This study tested the hypothesis that Finnish sauna bathing acutely improves peripheral flow-mediated dilation (FMD) in middle-aged and older adults with stable coronary artery disease (CAD).

Increased Circulating Levels of Neutrophil Extracellular Traps During Cardiopulmonary Bypass.

Background: The intensity of inflammatory response triggered by cardiopulmonary bypass (CPB) during cardiac surgery has been associated with adverse outcomes. Neutrophils might contribute to organ injury through the liberation of DNA histone-based structures named "neutrophil extracellular traps" (NETs). Our objective was to assess circulating NETs levels before and after cardiac surgery in low-risk and high-risk patients.