Toll-like Receptors 1, 3 and 7 Activate Distinct Genetic Features of NF-κB Signaling and γ-Protocadherin Expression in Human Cardiac Fibroblasts.

Fibroblasts play a pivotal role in key processes within the heart, particularly in cardiac remodeling that follows both ischemic and non-ischemic injury. During remodeling, fibroblasts drive fibrosis and inflammation by reorganizing the extracellular matrix and modulating the immune response, including toll-like receptor (TLR) activation, to promote tissue stabilization. Building on findings from our prior research on heart tissue from patients with advanced coronary artery disease and aortic valve disease, this study sought to explore specific effects of TLR1, TLR3, and TLR7 activation on NF-κB signaling, proinflammatory cytokine production, and γ-protocadherin expression in cardiac fibroblasts.

Machine learning evaluation for identification of M-proteins in human serum.

Serum electrophoresis (SPEP) is a method used to analyze the distribution of the most important proteins in the blood. The major clinical question is the presence of monoclonal fraction(s) of antibodies (M-protein/paraprotein), which is essential for the diagnosis and follow-up of hematological diseases, such as multiple myeloma. Recent studies have shown that machine learning can be used to assess protein electrophoresis by, for example, examining protein glycan patterns to follow up tumor surgery.

Regional transcriptomic profiling reveals immune system enrichment in nonfailing atria and all chambers of the failing human heart.

The different chambers of the human heart demonstrate regional physiological traits and may be differentially affected during pathological remodeling, resulting in heart failure. Few previous studies, however, have characterized the different chambers at a transcriptomic level. We, therefore, conducted whole tissue RNA sequencing and gene set enrichment analysis of biopsies collected from the four chambers of adult failing ( = 8) and nonfailing ( = 11) human hearts.

Metagenomic sequencing of human cardiac tissue reveals Microbial RNA which correlates with Toll-like receptor-associated inflammation in patients with heart disease.

Cardiovascular disease (CVD) is strongly associated with chronic low-grade inflammation, involving activated Toll-like receptors and their downstream cellular machinery. Moreover, CVD and other related inflammatory conditions are associated with infiltration of bacteria and viruses originating from distant body sites. Thus, in this study we aimed to map the presence of microbes in the myocardium of patients with heart disease that we previously found to display upregulated Toll-like receptor signaling.

Salivary biglycan-neo-epitope-BGN: A novel surrogate biomarker for equine osteoarthritic sub-chondral bone sclerosis and to monitor the effect of short-term training and surface arena.

Objective: We aimed to delineate a novel soluble Biglycan Neo-epitope-BGN262 in saliva from young reference and osteoarthritic horses in conjunction with the influence of short-term training exercise, riding surface hardness, circadian rhythm, and feeding on its soluble levels.

Design: A custom-made inhibition ELISA was used for the quantification of BGN262 in saliva. Cohort 1: A cross-sectional study comprising reference (N ​= ​19) and OA horses (N ​= ​9) with radiographically classified subchondral bone sclerosis.

Human intracardiac SSEA4+CD34 cells show features of cycling, immature cardiomyocytes and are distinct from Side Population and C-kit+CD45- cells.

Cardiomyocyte proliferation has emerged as the main source of new cardiomyocytes in the adult. Progenitor cell populations may on the other hand contribute to the renewal of other cell types, including endothelial and smooth muscle cells. The phenotypes of immature cell populations in the adult human heart have not been extensively explored.

Markedly reduced myocardial expression of γ-protocadherins and long non-coding RNAs in patients with heart disease.

Background: Adverse cardiac remodeling and tissue damage following heart disease is strongly associated with chronic low grade inflammation. The mechanisms underlying persisting inflammatory signals are not fully understood, but may involve defective and/or non-responsive transcriptional and post-transcriptional regulatory mechanisms. In the current study, we aimed to identify novel mediators and pathways involved in processes associated with inflammation in the development and maintenance of cardiac disease.

Galectin-1 is inversely associated with type 2 diabetes independently of obesity - A SCAPIS pilot study.

Objectives: Galectin-1 is a recently discovered adipokine that increases with obesity and increased energy intake in adipose tissue. Our aim was to assess whether serum galectin-1 is associated with type 2 diabetes (T2D) and other parameters of the metabolic syndrome independently of body mass index (BMI) in a cohort from the general population.

Methods: In this cross-sectional population-based cohort study from the western part of Sweden, we investigated associations between serum galectin-1, clinical characteristics and inflammatory markers in 989 women and men aged 50-65 years [part of the Swedish CArdioPulmonary bioImage Study (SCAPIS) pilot cohort].

Wide QRS-T angles are associated with markers of increased inflammatory activity independently of hypertension and diabetes.

Background: Wide QRS-T angles and inflammatory activity are markers of future cardiovascular events including sudden cardiac death (SCD). The association between wide QRS-T angles and inflammatory activation is however not fully understood.

Methods: 1,094 study participants of both sexes, 50-64 years old, were included from a randomly selected population-based cohort as a part of the Swedish CArdioPulmonary bioImage Study (SCAPIS) pilot study.

Toll-like receptor-mediated inflammation markers are strongly induced in heart tissue in patients with cardiac disease under both ischemic and non-ischemic conditions.

Background: A sustained low grade inflammatory state is a recognized feature of various diseases, including cardiovascular disease. This state of chronic inflammation involves activation of Toll-like receptor (TLR) signaling. However, little is known regarding the genetic profile of TLR components in cardiac tissue from patients with cardiac disease.

Cartilage oligomeric matrix protein neoepitope in the synovial fluid of horses with acute lameness: A new biomarker for the early stages of osteoarthritis.

Background: Clinical tools to diagnose the early changes of osteoarthritis (OA) that occur in the articular cartilage are lacking.

Objectives: We sought to identify and quantify a novel cartilage oligomeric matrix protein (COMP) neoepitope in the synovial fluid from the joints of healthy horses and those with different stages of OA.

Study Design: In vitro quantitative proteomics and assay development with application in synovial fluids samples obtained from biobanks of well-characterised horses.

Imaging of Intracellular and Extracellular ROS Levels in Atherosclerotic Mouse Aortas Ex Vivo: Effects of Lipid Lowering by Diet or Atorvastatin.

Objective: The first objective was to investigate if intracellular and extracellular levels of reactive oxygen species (ROS) within the mouse aorta increase before or after diet-induced lesion formation. The second objective was to investigate if intracellular and extracellular ROS correlates to cell composition in atherosclerotic lesions. The third objective was to investigate if intracellular and extracellular ROS levels within established atherosclerotic lesions can be reduced by lipid lowering by diet or atorvastatin.

The VLDL receptor promotes lipotoxicity and increases mortality in mice following an acute myocardial infarction.

Impaired cardiac function is associated with myocardial triglyceride accumulation, but it is not clear how the lipids accumulate or whether this accumulation is detrimental. Here we show that hypoxia/ischemia-induced accumulation of lipids in HL-1 cardiomyocytes and mouse hearts is dependent on expression of the VLDL receptor (VLDLR). Hypoxia-induced VLDLR expression in HL-1 cells was dependent on HIF-1α through its interaction with a hypoxia-responsive element in the Vldlr promoter, and VLDLR promoted the endocytosis of lipoproteins.

Physical training after percutaneous coronary intervention in patients with stable angina: effects on working capacity, metabolism, and markers of inflammation.

Objective: Physical activity is effective in primary and secondary prevention of cardiovascular disease. In this study, we tested the hypothesis that exercise training improves glucose and lipid metabolism, the inflammatory/anti-inflammatory balance, and the outcome of elective percutaneous coronary intervention (PCI) in patients with stable coronary disease.

Methods: Sixty-two patients scheduled to undergo PCI for stable angina were randomized to intensive physical activity (n=33) consisting of home-based exercise on a bicycle ergometer or maintain their usual sedentary life (n=29).

Myocardial release of FKBP12 and increased production of FKBP12.6 in ischemia and reperfusion experimental models.

Background: Coronary artery occlusion and reperfusion may trigger reversible and irreversible ischemic and reperfusion injury. The primary aim of this study was to evaluate protein release into the myocardium in a porcine model during ischemia and reperfusion to search for clarifying models for reperfusion injury and secondarily to investigate release and production of the immunophilins FKBP12/12.6 in this model and in cell cultures.

Release of protein as well as activity of MMP-9 from unstable atherosclerotic plaques during percutaneous coronary intervention.

Objectives: Few studies have investigated the composition of unstable coronary plaques in vivo in humans. The aims of this study were to investigate if substances released from plaques during percutaneous coronary intervention (PCI) under distal protection could give information about plaque composition and also indicate possible biomarkers in plasma that may be used to identify patients at risk.

Methods And Results: Twenty patients with acute coronary syndromes undergoing PCI with distal protection were included.

C-reactive protein, interleukin-6, secretory phospholipase A2 group IIA and intercellular adhesion molecule-1 in the prediction of late outcome events after acute coronary syndromes.

Objective: We investigated whether levels of C-reactive protein (CRP), interleukin-6 (IL-6), secretory phospholipase A(2) group IIA (sPLA(2)-IIA) and intercellular adhesion molecule-1 (ICAM-I) predict late outcomes in patients with acute coronary syndromes (ACS).

Design: Prospective longitudinal study. CRP (mg L(-1)), IL-6 (pg mL(-1)), sPLA(2)-IIA (ng mL(-1)) and ICAM-1 (ng mL(-1)) were measured at days 1 (n = 757) and 4 (n = 533) after hospital admission for ACS.

Inhibitory effect of known antioxidants and of press juice from herring (Clupea harengus) light muscle on the generation of free radicals in human monocytes.

Reactive oxygen species (ROS) can cause oxidative stress, which has been linked to various diseases. It has been suggested that antioxidant-rich foods can reduce such oxidative stress. However, the lack of suitable model systems to screen for in vivo effects of food-derived antioxidants has prevented a clear consensus in this area.

Secretory phospholipase A2 group V: lesion distribution, activation by arterial proteoglycans, and induction in aorta by a Western diet.

Objective: To study the distribution of group V secretory phospholipase A2 (sPLA2) in human and mouse lesions and compare its expression by human vascular cells, its activity toward lipoproteins, and the interaction with arterial proteoglycans (proteoglycans) with those of sPLA2-IIA. In addition, we also investigated the effect of a Western diet and lipopolysaccharide challenge on the aortic expression of these enzymes in mouse models.

Methods And Results: Immunohistochemistry showed sPLA2-V in human and mouse lesions to be associated with smooth muscle cells and also surrounding foam cells in lipid core areas.

CRP, interleukin-6, secretory phospholipase A2 group IIA, and intercellular adhesion molecule-1 during the early phase of acute coronary syndromes and long-term follow-up.

Objectives: The objectives of this study were to examine the time course of the inflammatory response in acute coronary syndromes (ACS) and to assess the markers of inflammation and their relation to disease severity.

Methods: We prospectively studied 134 patients with ACS who survived for at least 30 months. The patients were divided into four groups: acute myocardial infarction (MI) with (n=54) or without (n=46) ST-segment elevation and unstable angina with (n=14) or without (n=20) increased risk.

Regulation and splicing of scavenger receptor class B type I in human macrophages and atherosclerotic plaques.

Background: The protective role of high-density lipoprotein (HDL) in the cardiovascular system is related to its role in the reverse transport of cholesterol from the arterial wall to the liver for subsequent excretion via the bile. Scavenger receptor class B type I (SR-BI) binds HDL and mediates selective uptake of cholesterol ester and cellular efflux of cholesterol to HDL. The role of SR-BI in atherosclerosis has been well established in murine models but it remains unclear whether SR-BI plays an equally important role in atherosclerosis in humans.

Growth hormone induces myocardial expression of creatine transporter and decreases plasma levels of IL-1beta in rats during early postinfarct cardiac remodeling.

Growth hormone has been proposed as a potential new therapeutic agent for treatment of myocardial infarction (MI) and congestive heart failure (CHF). The purpose of this study was to evaluate the effects of GH on: (a) myocardial expression of creatine transporter (CreaT) during early postinfarct remodeling, (b) myocardial levels of total creatine (TCr) and adenine pool (TAN) and (c) plasma levels of inflammatory cytokines interleukin-1beta (IL-1beta), tumor-necrosis-factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in rat model of postinfarct cardiac remodeling. Myocardial infarction (MI) was induced by ligation of the left coronary artery in male Sprague-Dawley rats (200-250 g).

Circulating ICAM-1 (intercellular cell-adhesion molecule 1) is associated with early stages of atherosclerosis development and with inflammatory cytokines in healthy 58-year-old men: the Atherosclerosis and Insulin Resistance (AIR) study.

There is a lack of data on circulating levels of cell-adhesion molecules in relation to subclinical atherosclerosis measured in both the carotid and femoral arteries in humans. The aim of the present study was to investigate the relationship between clinically silent atherosclerosis and cell-adhesion molecules, and to explore the relationship between these molecules, C-reactive protein and the inflammatory cytokines interleukin-6, tumour necrosis factor-alpha (TNF-alpha), soluble TNF-alpha receptor p55 and soluble TNF-alpha receptor p75. The study group (n=391) consisted of clinically healthy 58-year-old men recruited from the general population.

Effects of simvastatin and atorvastatin on inflammation markers in plasma.

Objectives: To study the effect of statins on plasma markers for inflammation.

Design: Patients with hypercholesterolemia were randomized in one of the following treatments: Simvastatin (S) + placebo: S 40 mg for 6 weeks - S 80 mg for 6 weeks - S 80 mg for 24 weeks and Atorvastatin (A) + placebo: A 20 mg for 6 weeks - A 40 mg for 6 weeks - A 80 mg for 24 weeks.

Subjects: Forty-seven patients with hypercholesterolemia were recruited in four different outpatient clinics.