Publications by authors named "Martin G Sirois"

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).

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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).

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  • ERK3/MAPK6 activates MK5, influencing cardiac fibroblast function and hypertrophy in male mice.
  • Male MK5 haplo-deficient mice show reduced cardiac hypertrophy and decreased Col1a1 mRNA when faced with increased cardiac afterload.
  • The study reveals that reduced ERK3 leads to lower heart mass and impacts fibroblast behavior, highlighting ERK3's crucial role in cardiac fibroblast biology.
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  • Heart failure (HF) is associated with chronic inflammation and involves two types of neutrophils: high-density neutrophils (HDNs) and low-density neutrophils (LDNs), with LDNs often increasing in various diseases and releasing inflammatory substances.
  • This study isolated and measured these neutrophil subtypes and their activities in individuals with HF, including both HFrEF and HFpEF patients, compared to healthy volunteers.
  • Results showed significantly higher counts of both HDNs and LDNs in HF patients, particularly those with HFpEF, linking LDN counts to increased inflammatory markers and the formation of neutrophil extracellular traps (NETs).
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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.

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  • Lean patients with NAFLD can experience cardiac issues without already having metabolic problems or obesity.
  • Researchers studied mice with liver mitochondrial deficiencies, which develop liver fat but not obesity, to understand this connection.
  • The findings revealed that male mice showed more significant cardiac dysfunction and metabolic disturbances than female mice, who had different cardiometabolic problems involving liver and cardiac lipid imbalances.
  • This research highlights how liver metabolism can lead to cardiac issues differently in males and females, emphasizing the need to explore these gender-related differences further in lean NAFLD.
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  • Type 2 diabetes (T2D) is linked to increased low-density neutrophils (LDNs), which contribute to inflammation by releasing inflammatory cytokines and neutrophil extracellular traps (NETs).
  • LDN counts and various inflammatory biomarkers, such as citrullinated H3 histone and myeloperoxidase, were significantly higher in T2D patients compared to healthy volunteers, indicating heightened inflammatory activity.
  • Isolated LDNs from T2D patients showed greater NET formation and adhesion capabilities on human extracellular matrix compared to those from healthy individuals, highlighting the pro-inflammatory role of LDNs in T2D.
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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.

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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.

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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.

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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.

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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).

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  • - In a study of patients with moderate to severe aortic stenosis (AS), researchers examined the relationship between two biomarkers, GDF-15 and sST2, and indicators of cardiovascular risk and LV function.
  • - Elevated levels of GDF-15 were linked to worse left ventricular (LV) function and decreased functional capacity, as measured by tests like the 6-minute walk test and gait speed.
  • - Although GDF-15 did not predict AS severity, its high levels may serve as a potential single biomarker to identify patients at greater risk for poor outcomes in AS.
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  • HFpEF is linked to chronic inflammation, which may worsen in patients with type 2 diabetes due to neutrophils releasing pro-inflammatory cytokines.
  • Blood samples were taken from groups including those with diabetes, HFpEF, HFpEF with diabetes, and healthy controls to analyze cytokine levels.
  • Results showed reduced nitric oxide and increased adhesion molecules and inflammatory cytokine levels in patients with HFpEF and diabetes, indicating heightened inflammation in these groups compared to healthy individuals.
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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.

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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.

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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.

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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.

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  • MK2-null mice show normal survival rates and initial cardiac function, but exhibit early signs of diastolic dysfunction and altered heart rate dynamics.
  • MK2 deficiency results in increased expression of key metabolic genes and affects mitochondrial sensitivity in the heart.
  • The findings suggest that MK2 plays a crucial role in autonomic heart regulation, mitochondrial function, and early cardiac remodeling during pressure overload.
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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.

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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.

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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.

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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.

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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).

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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.

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