Myo-inositol trispyrophosphate prevents right ventricular failure and improves survival in monocrotaline-induced pulmonary hypertension in the rat.

Background And Purpose: Pulmonary hypertension (PH) results from pulmonary vasculopathy, initially leading to a compensatory right ventricular (RV) hypertrophy, and eventually to RV failure. Hypoxia can trigger both pulmonary vasculopathy and RV failure. Therefore, we tested if myo-inositol trispyrophosphate (ITPP), which facilitates oxygen dissociation from haemoglobin, can relieve pulmonary vasculopathy and RV hypoxia, and eventually prevent RV failure and mortality in the rat model of monocrotaline-induced PH.

TGF-β Signalling Regulates Cytokine Production in Inflammatory Cardiac Macrophages during Experimental Autoimmune Myocarditis.

Myocarditis is characterized by an influx of inflammatory cells, predominantly of myeloid lineage. The progression of myocarditis to a dilated cardiomyopathy is markedly influenced by TGF-β signalling. Here, we investigate the role of TGF-β signalling in inflammatory cardiac macrophages in the development of myocarditis and post-inflammatory fibrosis.

TNF-α protects from exacerbated myocarditis and cardiac death by suppressing expansion of activated heart-reactive CD4+ T cells.

Aims: Tumour necrosis factor α (TNF-α) represents a classical pro-inflammatory cytokine, and its increased levels positively correlate with the severity of many cardiovascular diseases. Surprisingly, some heart failure patients receiving high doses of anti-TNF-α antibodies showed serious health worsening. This work aimed to examine the role of TNF-α signalling on the development and progression of myocarditis and heart-specific autoimmunity.

T Lymphocyte-Derived Exosomes Transport MEK1/2 and ERK1/2 and Induce NOX4-Dependent Oxidative Stress in Cardiac Microvascular Endothelial Cells.

Background: Activation of endothelial cells by inflammatory mediators secreted by CD4 T lymphocytes plays a key role in the inflammatory response. Exosomes represent a specific class of signaling cues transporting a mixture of proteins, nucleic acids, and other biomolecules. So far, the impact of exosomes shed by T lymphocytes on cardiac endothelial cells remained unknown.

Inhaled silica nanoparticles exacerbate atherosclerosis through skewing macrophage polarization towards M1 phenotype.

Background And Aims: Exposure to environmental nanoparticles is related to the adverse impact on health, including cardiovascular system. Various forms of nanoparticles have been reported to interact with endothelium and induce inflammation. However, the potential role of nanoparticles in the pathogenesis of atherosclerosis and their mechanisms of action are still unclear.

Regulation of Monocyte Adhesion and Type I Interferon Signaling by CD52 in Patients With Systemic Sclerosis.

Objective: Systemic sclerosis (SSc) is characterized by dysregulation of type I interferon (IFN) signaling. CD52 is known for its immunosuppressive functions in T cells. This study was undertaken to investigate the role of CD52 in monocyte adhesion and type I IFN signaling in patients with SSc.

Angiotensin II receptor 1 controls profibrotic Wnt/β-catenin signalling in experimental autoimmune myocarditis.

Aims: Angiotensin (Ang) II signalling has been suggested to promote cardiac fibrosis in inflammatory heart diseases; however, the underlying mechanisms remain obscure. Using Agtr1a-/- mice with genetic deletion of angiotensin receptor type 1 (ATR1) and the experimental autoimmune myocarditis (EAM) model, we aimed to elucidate the role of Ang II-ATR1 pathway in development of heart-specific autoimmunity and post-inflammatory fibrosis.

Methods And Results: EAM was induced in wild-type (WT) and Agtr1a-/- mice by subcutaneous injections with alpha myosin heavy chain peptide emulsified in complete Freund's adjuvant.

Complexity of TNF-α Signaling in Heart Disease.

Heart disease is a leading cause of death with unmet clinical needs for targeted treatment options. Tumor necrosis factor alpha (TNF-α) represents a master pro-inflammatory cytokine that plays an important role in many immunopathogenic processes. Anti-TNF-α therapy is widely used in treating autoimmune inflammatory disorders, but in case of patients with heart disease, this treatment was unsuccessful or even harmful.

Haploinsufficient and Mice Are Not Protected from Cardiac Inflammation and Postinflammatory Fibrosis in Experimental Autoimmune Myocarditis.

Progressive cardiac fibrosis is a common cause of heart failure. Rho-associated, coiled-coil-containing protein kinases (ROCKs) have been shown to enhance fibrotic processes in the heart and in other organs. In this study, using wild-type, and haploinsufficient mice and mouse model of experimental autoimmune myocarditis (EAM) we addressed the role of ROCK1 and ROCK2 in development of myocarditis and postinflammatory fibrosis.

Invasive bronchial fibroblasts derived from asthmatic patients activate lung cancer A549 cells .

Epidemiological data suggests that there are functional links between bronchial asthma and lung carcinogenesis. Bronchial fibroblasts serve a prominent role in the asthmatic process; however, their involvement in lung cancer progression remains unaddressed. To estimate the effect of the asthmatic microenvironment on the invasiveness of lung cancer cells, the present study compared the behavior of human non-small cell lung cancer A549 cells exposed to the signals from human bronchial fibroblasts (HBFs) derived from non-asthmatic donors (NA HBFs) and from asthmatic patients (AS HBFs).