Shedding of membrane complement inhibitors CD59 and CD46 into the circulation is associated with poor prognosis in acute coronary syndrome patients: a cohort study.

Introduction: The role of the complement inhibitory proteins CD46 and CD59 in the immune response to an acute coronary syndrome (ACS) is unknown. We investigated the relationships between the shedding of CD46 and CD59 into the circulation, reflected by plasma levels of soluble CD46 and CD59, and the risk for post-ACS complications.

Methods: We measured plasma sCD46 and sCD59 in a cohort of 546 ACS patients within 24 h after hospital admission, and after 6-weeks in a subgroup of 114 patients.

IL1RAP Blockade With a Monoclonal Antibody Reduces Cardiac Inflammation and Preserves Heart Function in Viral and Autoimmune Myocarditis.

Background: Currently, there are no therapies targeting specific pathogenic pathways in myocarditis. IL (interleukin)-1 blockade has shown promise in preclinical studies and case reports. We hypothesized that blockade of IL1RAP (IL-1 receptor accessory protein), a shared subunit of the IL-1, IL-33, and IL-36 receptors, could be more efficient than IL-1 blockade alone.

Short-term S100A8/A9 Blockade Promotes Cardiac Neovascularization after Myocardial Infarction.

Acute-phase inhibition of the pro-inflammatory alarmin S100A8/A9 improves cardiac function post-myocardial infarction (MI), but the mechanisms underlying the long-term benefits of this short-term treatment remain to be elucidated. Here, we assessed the effects of S100A8/A9 blockade with the small-molecule inhibitor ABR-238901 on myocardial neovascularization in mice with induced MI. The treatment significantly reduced S100A9 and increased neovascularization in the myocardium, assessed by CD31 staining.

Increasing plasma calprotectin (S100A8/A9) is associated with 12-month mortality and unfavourable functional outcome in critically ill COVID-19 patients.

Background: Calprotectin (S100A8/A9) is a pro-inflammatory mediator primarily released from neutrophils. Previous studies have revealed associations between plasma calprotectin, disease severity and in-hospital mortality in unselected COVID-19 patients.

Objective: We aimed to assess whether plasma calprotectin dynamics during the first week of intensive care are associated with mortality and functional outcome in critically ill COVID-19 patients.

Interleukin-1 receptor accessory protein blockade limits the development of atherosclerosis and reduces plaque inflammation.

Aims: The interleukin-1 receptor accessory protein (IL1RAP) is a co-receptor required for signalling through the IL-1, IL-33, and IL-36 receptors. Using a novel anti-IL1RAP-blocking antibody, we investigated the role of IL1RAP in atherosclerosis.

Methods And Results: Single-cell RNA sequencing data from human atherosclerotic plaques revealed the expression of IL1RAP and several IL1RAP-related cytokines and receptors, including IL1B and IL33.

Special Issue "COVID-19 Coagulopathy: Advances on Pathophysiology and Therapies".

The Special Issue on COVID-19 coagulopathy initiated one year ago aimed to shed light on the mechanisms underlying the changes in the coagulation status making SARS-CoV-2 infection such a tough adversary for every one of the medical specialties encountering it, along with overseeing the therapeutic applications derived from the current understanding of these mechanisms [...

Elevated soluble LOX-1 predicts risk of first-time myocardial infarction.

Background: There is an unmet clinical need for novel therapies addressing the residual risk in patients receiving guideline preventive therapy for coronary heart disease. Experimental studies have identified a pro-atherogenic role of the oxidized LDL receptor LOX-1. We investigated the association between circulating soluble LOX-1 (sLOX-1) and the risk for development of myocardial infarction.

Invariant natural killer T cells and incidence of first-time coronary events: a nested case-control study.

Aims: Invariant natural killer T (iNKT) cells, a T cell subset that is CD1d-restricted and expresses a semi-invariant T cell receptor, have been proposed to contribute to dyslipidaemia-driven cardiovascular disease due to their ability to specifically recognize lipid antigens. Studies in mice have attributed pro-atherogenic properties to iNKT cells, but studies in humans investigating associations of iNKT cells with incident coronary events (CE) are lacking.

Methods And Results: Here, we used flow cytometry to enumerate circulating iNKT cells (CD3 CD1d-PBS57-Tetramer) in a case-control cohort nested within the prospective population-based Malmö Diet and Cancer Study ( = 416) to explore associations with incident first-time CE during a median follow-up of 14 years.

Therapeutic S100A8/A9 blockade inhibits myocardial and systemic inflammation and mitigates sepsis-induced myocardial dysfunction.

Background And Aims: The triggering factors of sepsis-induced myocardial dysfunction (SIMD) are poorly understood and are not addressed by current treatments. S100A8/A9 is a pro-inflammatory alarmin abundantly secreted by activated neutrophils during infection and inflammation. We investigated the efficacy of S100A8/A9 blockade as a potential new treatment in SIMD.

Vascular smooth muscle-specific YAP/TAZ deletion triggers aneurysm development in mouse aorta.

Inadequate adaption to mechanical forces, including blood pressure, contributes to development of arterial aneurysms. Recent studies have pointed to a mechanoprotective role of YAP and TAZ in vascular smooth muscle cells (SMCs). Here, we identified reduced expression of YAP1 in human aortic aneurysms.

S100A8∕A9 is a valuable biomarker and treatment target to detect and modulate neutrophil involvement in myocardial infarction.

Myocardial infarction (MI) leads to irreversible ischemic damage of the heart muscle and is the leading cause of heart failure. The ischemic cardiac injury triggers a potent local and systemic immune response. In the acute phase post-MI, neutrophils infiltrate the myocardium in large numbers and induce further cardiomyocyte death, expanding the infarcted area.

Long-term Safety of Revascularization Deferral Based on Instantaneous Wave-Free Ratio or Fractional Flow Reserve.

Background: Deferral of coronary revascularization is safe whether guided by instantaneous wave-free ratio (iFR) or by fractional flow reserve (FFR). We aimed to assess long-term outcomes in patients deferred from revascularization based on iFR or FFR in a large real-world population.

Methods: From 2013 through 2017, 201,933 coronary angiographies were registered in the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART).

S100A9 induces reactive oxygen species-dependent formation of neutrophil extracellular traps in abdominal sepsis.

Recent evidence suggests that targeting S100A9 reduces pathological inflammation in abdominal sepsis. Herein, we investigated the role of S100A9 in neutrophil extracellular trap (NET) formation in septic lung damage. NETs were detected by electron microscopy in the lung and by confocal microscopy in vitro.

Organizational and patient-level predictors for attaining key risk factor targets in cardiac rehabilitation after myocardial infarction: The Perfect-CR study.

Background: Benefits of cardiac rehabilitation (CR) programme components on attaining risk factor targets post-myocardial infarction (MI) and their predictive strength relative to patient characteristics remain unclear. We aimed to identify organizational and patient-level predictors of risk factor target attainment at one-year post-MI.

Methods: In this observational study data on CR organization at 78 Swedish CR centres was collected and merged with patient-level registry data (n = 7549).

Effect of a Lifestyle-Focused Web-Based Application on Risk Factor Management in Patients Who Have Had a Myocardial Infarction: Randomized Controlled Trial.

Background: Cardiac rehabilitation is central in reducing mortality and morbidity after myocardial infarction. However, the fulfillment of guideline-recommended cardiac rehabilitation targets is unsatisfactory. eHealth offers new possibilities to improve clinical care.

Targeting S100A9 Reduces Neutrophil Recruitment, Inflammation and Lung Damage in Abdominal Sepsis.

S100A9, a pro-inflammatory alarmin, is up-regulated in inflamed tissues. However, the role of S100A9 in regulating neutrophil activation, inflammation and lung damage in sepsis is not known. Herein, we hypothesized that blocking S100A9 function may attenuate neutrophil recruitment in septic lung injury.

Transcriptional Profiling and Functional Analysis of N1/N2 Neutrophils Reveal an Immunomodulatory Effect of S100A9-Blockade on the Pro-Inflammatory N1 Subpopulation.

Neutrophils have been classically viewed as a homogenous population. Recently, neutrophils were phenotypically classified into pro-inflammatory N1 and anti-inflammatory N2 sub-populations, but the functional differences between the two subtypes are not completely understood. We aimed to investigate the phenotypic and functional differences between N1 and N2 neutrophils, and to identify the potential contribution of the S100A9 alarmin in neutrophil polarization.

Safety of early hospital discharge following admission with ST-elevation myocardial infarction treated with percutaneous coronary intervention: a nationwide cohort study.

Background: The Second Primary Angioplasty in Myocardial Infarction (PAMI-II) risk score is recommended by guidelines to identify low-risk patients with ST-elevation myocardial infarction (STEMI) for an early discharge strategy.

Aims: We aimed to assess the safety of early discharge (≤2 days) for low-risk STEMI patients treated with primary percutaneous coronary intervention (PCI).

Methods: Using nationwide data from the SWEDEHEART registry, we identified patients with STEMI treated with primary PCI during the period 2009-2017, of whom 8,092 (26.

S100A9 Links Inflammation and Repair in Myocardial Infarction.

Rationale: The alarmin S100A9 has been identified as a potential therapeutic target in myocardial infarction. Short-term S100A9 blockade during the inflammatory phase post-myocardial infarction inhibits systemic and cardiac inflammation and improves cardiac function long term.

Objective: To evaluate the impact of S100A9 blockade on postischemic cardiac repair.

Association between attending exercise-based cardiac rehabilitation and cardiovascular risk factors at one-year post myocardial infarction.

Background: Randomized trials confirm the benefits of exercise-based cardiac rehabilitation on cardiovascular risk factors. Whether exercise-based cardiac rehabilitation provides the same favourable effects in real-life cardiac rehabilitation settings, in the modern era of myocardial infarction treatment, is less well known. We examined the association between attending exercise-based cardiac rehabilitation and improvements in cardiovascular risk factors at one-year post myocardial infarction in patients included in the Swedish heart disease registry, SWEDEHEART.