endothelin-1 and Sarcoidosis--Pulmonary

Pulmonary hypertension (PH) is a well-recognized complication of sarcoidosis. Patients with sarcoidosis-associated PH (SAPH) have poorer functional status and greater supplemental oxygen requirements than sarcoidosis patients without PH, and are more likely to be listed for lung transplantation. PH is an independent risk factor for mortality in sarcoidosis patients awaiting lung transplantation. The pathophysiology of SAPH is complex, with multiple mechanisms contributing to pathogenesis, including the fibrous destruction of the pulmonary vascular bed, extrinsic compression of the central pulmonary vessels and an intrinsic vasculopathy. Recognition of SAPH may be delayed as it can be masked by the clinical picture of underlying pulmonary sarcoidosis, and right heart catheter remains the gold-standard for diagnosis. Management of SAPH is based on reversal of resting hypoxaemia, treatment of comorbidities and treatment of the underlying sarcoidosis. The use of corticosteroids in SAPH is controversial. Specific PH therapy is not routinely recommended in SAPH as there are no successful placebo-controlled trials, although there is limited data to suggest that endothelin receptor antagonists and phosphodiesterase-5 inhibitors may be useful.

Topics: Cardiomyopathies; Endothelin-1; Humans; Hypertension, Pulmonary; Lung; Natriuretic Peptide, Brain; Sarcoidosis, Pulmonary; Ultrasonography; Vasoconstriction

Endothelin-I (ET-I) levels in BALF of symptomatic (n = 7) and asymptomatic (n = 10) asthmatic patients, sarcoidosis (n = 10), allergic alveolitis (n = 6) and healthy volunteers (n = 6) was evaluated. In all patients BALF level of endothelin-I was assessed by radioimmunoassay. We observed that patients with symptomatic asthma had more increased amounts of ET-I in BALF in comparison with asymptomatic asthmatics, patients with sarcoidosis, allergic alveolitis and control group.. 1. Presence of ET-I in BALF indicates that this peptide is involved in the pathogenesis of bronchial asthma, sarcoidosis and allergic alveolitis. 2. Endothelin-I is involved in bronchial smooth muscle contraction.

Topics: Adult; Alveolitis, Extrinsic Allergic; Asthma; Bronchoalveolar Lavage Fluid; Endothelin-1; Female; Humans; Male; Middle Aged; Respiratory Tract Diseases; Sarcoidosis, Pulmonary

To assess the role of angiogenic factors (vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1) in interstitial lung diseases (ILD), such as fibrosing alveolitis, sarcoidosis.. The blood levels of endothelial dysfunction and neoangiogenesis markers (ET-1 and VEGF) were investigated in 96 patients with different clinical forms of ILD at it different stages; the found changes were compared with the clinical and morphological manifestations of the disease.. It has been ascertained that regardless of the clinical type of ILD, there is a correlation between the blood levels of VEGF and ET-1 and the intensity of lung neoangiogenesis, the expression of VEGF by the endothelium of newly formed blood vessels, the production of angiogenic factors, the degree of endothelial dysfunction, the extent of pulmonary fibrosis, the degree of pulmonary vascular remodeling, and the severity of pulmonary hypertension. The findings suggest that the markers of neoangiogenesis play an important role in the mechanisms of ILD progression.. The study of these parameters in the blood may be used to clarify the activity and prognosis of ILD.

Topics: Adult; Aged; Aged, 80 and over; Angiogenesis Inhibitors; Biomarkers; Case-Control Studies; Disease Progression; Endothelin-1; Endothelium, Vascular; Female; Humans; Idiopathic Pulmonary Fibrosis; Lung; Male; Middle Aged; Neovascularization, Pathologic; Pulmonary Circulation; Radiography; Respiratory Function Tests; Sarcoidosis, Pulmonary; Severity of Illness Index; Vascular Endothelial Growth Factor A

Sarcoidosis is a systemic granulomatous disease of unknown etiology, in which the lungs and intrathoracic lymph nodes are predominant sites of involvement. Pulmonary hypertension is a known complication of sarcoidosis. Treatment of sarcoidosis-associated pulmonary hypertension has traditionally focused on the initiation of systemic corticosteroids, but has had inconsistent results. We present a patient with sarcoidosis-associated pulmonary hypertension who achieved substantial clinical improvement with the dual endothelin receptor antagonist bosentan.

Topics: Antihypertensive Agents; Bosentan; Endothelin-1; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Middle Aged; Respiratory Function Tests; Sarcoidosis, Pulmonary; Sulfonamides

Pulmonary fibrosis in sarcoidosis is a significant cause of morbidity and mortality. Various factors have been intensely studied to define the pathogenesis of lung fibrosis in sarcoidosis. Endothelin (ET) consists of three isoforms and is known for its potent vasoconstrictor properties. ET plays an important role in the fibroproliferative process of interstitial lung diseases.. To investigate the role of ET in the progression of pulmonary fibrosis in sarcoidosis, ET-1 and ET-3 concentrations were measured in BAL fluid (BALF) in 22 non-smoking patients with sarcoidosis and in control subjects (n = 12). Immunoreactivity of ET-1 was also evaluated in alveolar macrophages (AMs) from sarcoidosis patients. To assess the effects of ET in BALF on fibroblast proliferation, human foetal lung fibroblasts were cultured with sarcoidosis or control BALFs in the presence or absence of the ET-receptor antagonist TAK-044.. ET-1 levels in sarcoidosis BALF were significantly higher than those in control, whereas ET-3 levels were not different between sarcoidosis and control. ET-1 levels were correlated with the number of AMs in BALF. ET-1-immunoreactivity was found mainly in AM of sarcoidosis BALF. Sarcoidosis BALF significantly stimulated fibroblast proliferation, compared with control BALF, and the fibroblast proliferation induced by sarcoidosis BALF was inhibited by TAK-044.. Increased levels of ET-1 in AM could enhance fibrogenesis in pulmonary sarcoidosis.

Topics: Adult; Aged; Biomarkers; Bronchoalveolar Lavage Fluid; Cell Proliferation; Disease Progression; Endothelin-1; Female; Fibroblasts; Flow Cytometry; Humans; Immunohistochemistry; Macrophages, Alveolar; Male; Middle Aged; Sarcoidosis, Pulmonary

The phenotype of alveolar-associated fibroblasts (Afb) in sarcoidosis (SA) and idiopathic pulmonary fibrosis (IPF) is unclear. In the present study, we characterized the cytoskeletal proteins and the contraction properties in alveolar-associated fibroblasts recovered by bronchoalveolar lavage (BAL) in the two diseases. Afb were studied from BAL cells in eight IPF and seven SA patients. Cytoskeletal proteins were identified by ELISA and immunofluorescent methods. Biochemical measurements were done by dry chemistry. Contraction was performed by a gel contraction assay. Afb alpha-SM actin measured by ELISA was higher in IPF than in SA (p = 0.042). Vimentin, desmin, myosin, and fibroblast markers were expressed equally. Only in IPF did the Afb reveal the myofibroblast phenotype showing alpha-SM actin immunofluorescence labeling and, by electron microscopy, filaments with associated dense bodies with rough endoplasmic reticulum. Gel contraction showed that cells in IPF contracted significantly more than in SA (p = 0.046 IPF versus SA). The addition of ET-1 increased contraction in all groups. Dry chemistry analysis showed higher levels (p = 0.0065) of creatine phosphokinase (CPK), lower levels of glucose (p = 0.0082), and similar levels of Ca(2+) and lactate in the IPF and SA Afb. Dinitrofluorobenzene (DNFB), a potent inhibitor of CPK, completely abolished spontaneous cell contraction. Afb differentiates into myofibroblasts with different biochemical and energetic properties in IPF. Moreover, Afb from IPF patients showed increased contractile properties. This may explain the difference in the behavior patterns and outcomes of the two diseases.

Topics: Adult; Aged; Bronchoalveolar Lavage Fluid; Calcium; Cell Count; Cells, Cultured; Collagen; Creatine Kinase; Cytoskeletal Proteins; Endothelin-1; Enzyme-Linked Immunosorbent Assay; Female; Fibroblasts; Fluorescent Antibody Technique; Gels; Glucose; Humans; Lactic Acid; Male; Pulmonary Alveoli; Pulmonary Fibrosis; Sarcoidosis, Pulmonary

To evaluate the roles of the Endothelin-1 (ET-1) in pathogenesis of the patients with interstitial lung disease (ILD).. The ET-1 activities in the serum and BALF from 10 patients with sarcoidosis, 7 with idiopathic pulmonary fibrosis (IPF) and 8 normal subjects non-smokers were determined using the radio-immunoassay.. In the activities of ET-1 in the serum and BALF in the patients with sarcoiosis (62 +/- 29 and 17.0 +/- 2.4) ng/L and in the IPF (77 +/- 71 and 10 +/- 3) ng/L. was higher than those in the normal control subjects (20 +/- 8 and 4.0 +/- 0.6) ng/L. The activities of ET-1 in serum was negative correlated with PaO2 (r = -0.538, P < 0.01). The level of ET-1 in the BALF of the patient was positive correlated with total cells in BALF (r = 0.649, P < 0.01). The levels of ET-1 in the BALF in the sarcoidosis was positive correlated with the percentage of lymphocyte (r = 0.712, P < 0.01) but in patients with IPF was positive correlated with the percentage of neutrophil (r = 0.813, P < 0.01).. ET-1 might play an important role in pathogenic of the patients with sarcoidosis and IPF. The levels of ET-1 can act as the markers of activity of disease.

Topics: Adult; Bronchoalveolar Lavage Fluid; Cell Count; Endothelin-1; Female; Humans; Lymphocytes; Male; Middle Aged; Neutrophils; Pulmonary Fibrosis; Sarcoidosis, Pulmonary