Alveolar hypoxia induces organ-specific inflammasome-related inflammation in male mouse lungs.

Inflammation through activation of caspase-1, seems to play a role in pulmonary hypertension induced by alveolar hypoxia. Whether alveolar hypoxia induces caspase-1-mediated inflammation and influx of leukocytes in other organs than the lungs, is not known. Our aim was to explore sites of caspase-1-related inflammation in alveolar hypoxia.

Extreme altitude induces divergent mass reduction of right and left ventricle in mountain climbers.

Mountain climbing at high altitude implies exposure to low levels of oxygen, low temperature, wind, physical and psychological stress, and nutritional insufficiencies. We examined whether right ventricular (RV) and left ventricular (LV) myocardial masses were reversibly altered by exposure to extreme altitude. Magnetic resonance imaging and echocardiography of the heart, dual x-ray absorptiometry scan of body composition, and blood samples were obtained from ten mountain climbers before departure to Mount Everest or Dhaulagiri (baseline), 13.

Thromboembolic events after high-intensity training during cisplatin-based chemotherapy for testicular cancer: Case reports and review of the literature.

The randomized "Testicular cancer and Aerobic and Strength Training trial" (TAST-trial) aimed to evaluate the effect of high-intensity interval training (HIIT) on cardiorespiratory fitness during cisplatin-based chemotherapy (CBCT) for testicular cancer (TC). Here, we report on an unexpected high number of thromboembolic (TE) events among patients randomized to the intervention arm, and on a review of the literature on TE events in TC patients undergoing CBCT. Patients aged 18 to 60 years with a diagnosis of metastatic germ cell TC, planned for 3 to 4 CBCT cycles, were randomized to a 9 to 12 weeks exercise intervention, or to a single lifestyle counseling session.

Caspase-1 induces smooth muscle cell growth in hypoxia-induced pulmonary hypertension.

Lung diseases with hypoxia are complicated by pulmonary hypertension, leading to heart failure and death. No pharmacological treatment exists. Increased proinflammatory cytokines are found in hypoxic patients, suggesting an inflammatory pathogenesis.

Absence of the inflammasome adaptor ASC reduces hypoxia-induced pulmonary hypertension in mice.

Pulmonary hypertension is a serious condition that can lead to premature death. The mechanisms involved are incompletely understood although a role for the immune system has been suggested. Inflammasomes are part of the innate immune system and consist of the effector caspase-1 and a receptor, where nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3) is the best characterized and interacts with the adaptor protein apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC).

IL-18 and IL-12 synergy induces matrix degrading enzymes in the lung.

Interleukin (IL)-18 is a pro-inflammatory cytokine suggested to be involved in the development of pulmonary emphysema and inflammation. Studies involving immunology and cancer have revealed that IL-18 can have synergistic effects with IL-12. We have studied the presence of IL-18 and IL-12 receptors (IL-18R/IL-12R) in the lungs and whether IL-18 and IL-12, alone or in combination, have the ability to initiate the induction of mediators related to the development of emphysema and inflammation.

Lack of CCR7 induces pulmonary hypertension involving perivascular leukocyte infiltration and inflammation.

The chemokine receptor CCR7 regulates lymphocyte trafficking, and CCR7 deficiency induces infiltration of T and B cells adjacent to vessels in mouse lungs. Perivascular infiltration of T and B cells has also been found in human pulmonary arterial hypertension, and downregulation of the CCR7 receptor in circulating leukocytes of such patients has been observed. To investigate whether changes in the CCR7 system contribute to the pathogenesis of pulmonary hypertension, we utilized mice deficient of the CCR7 receptor.

Elevated levels of activin A in clinical and experimental pulmonary hypertension.

Activin A, a member of the transforming growth factor (TGF)-beta superfamily, is involved in regulation of tissue remodeling and inflammation. Herein, we wanted to explore a role for activin A in pulmonary hypertension (PH). Circulating levels of activin A and its binding protein follistatin were measured in patients with PH (n = 47) and control subjects (n = 14).

Diastolic dysfunction in alveolar hypoxia: a role for interleukin-18-mediated increase in protein phosphatase 2A.

Aims: Chronic obstructive pulmonary disease with alveolar hypoxia is associated with diastolic dysfunction in the right and left ventricle (LV). LV diastolic dysfunction is not caused by increased afterload, and we recently showed that reduced phosphorylation of phospholamban at serine (Ser) 16 may explain the reduced relaxation of the myocardium. Here, we study the mechanisms leading to the hypoxia-induced reduction in phosphorylation of phospholamban at Ser16.

Alveolar hypoxia induces left ventricular diastolic dysfunction and reduces phosphorylation of phospholamban in mice.

Chronic obstructive pulmonary disease (COPD) may lead to pulmonary hypertension (PH) and reduced function of the right ventricle (RV). However, COPD patients may also develop left ventricular (LV) diastolic dysfunction. We hypothesized that alveolar hypoxia induces LV diastolic dysfunction and changes in proteins governing Ca(2+) removal from cytosol during diastole.