Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0034065 (pulmonary embolism)
 14,979 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The plasma endothelin-1 (ET-1) level is elevated in patients with acute pulmonary thromboembolism (APE). Whether ET-1 is a pathogenic mediator or a simple marker of APE is not known. We investigated the role of ET-1 in hemodynamic dysfunction in APE through evaluating the effects of ET(A) receptor antagonist in an experimental APE model. We also examined ET-1 expression in embolized lungs. In a canine autologous blood clot pulmonary embolism model, ET(A) receptor antagonist ZD2574 (10 mg/kg, intravenous; ZD2574 group; n = 6) or vehicle (control group; n = 5) was administered. Hemodynamic and gas exchange parameters and plasma levels of ET-1 were serially measured. Prepro-ET-1 mRNA expression and the distribution of ET-1 peptide in lung tissues were also examined. With ZD2574 pulmonary arterial pressure and pulmonary vascular resistance significantly decreased, and were lower compared with the control group. The decrease in cardiac output was also less in the ZD2574 group. Plasma ET-1 levels increased after embolization. Prepro-ET-1 mRNA expression increased in embolized lungs and ET-1 peptide expression also increased in embolized lungs, particularly in the muscular pulmonary arteries, compared with normal lungs. These findings suggest that ET-1 partially contributes to hemodynamic derangements of APE, and that ET(A) receptor antagonists might constitute a useful therapeutic tool for APE.
 ...
PMID:Pathogenic role of endothelin 1 in hemodynamic dysfunction in experimental acute pulmonary thromboembolism. 1167 23

Acute pulmonary embolism (PE) is a life-threatening disease, and several vasoconstrictors, including endothelin-1 (ET-1), play a key role in vasoconstriction and hypoxemia during the development of PE. Rho kinase is activated by various vasoconstrictors resulting in vascular contraction and remodeling. Recent evidence has revealed an important role of Rho kinase in the pathogenesis of systemic and pulmonary vascular diseases. However, contribution of Rho kinase in PE remains unclear. We thus investigated the role of Rho kinase in the PE rat model induced by intrajugular administration of polystyrene microspheres (mean diameter, 26 microm). At 6 h following the administration of microspheres (1.5 ml/kg), right ventricular systolic pressure (RVSP) was higher in the PE than in the control rats (15.8 +/- 1.6 vs. 32.9 +/- 7.5 mmHg). Arterial oxygen tension was lower (92.3 +/- 12.5 vs. 66.0 +/- 17.7 Torr), and alveolar-arterial difference in oxygen partial pressure was higher (3.9 +/- 3.8 vs. 36.5 +/- 26.9 Torr) in the PE rats. Western blotting analysis revealed upregulation and downregulation in expression of vascular cell adhesion molecule-1 and endothelial nitric oxide synthase in lungs from the PE rats, respectively, and radioimmunoassay demonstrated an increase in plasma ET-1 levels. Lung Rho kinase alpha expression was greater in the PE rats. At 5 h following administration of microspheres (0.75 ml/kg), intravenous Rho kinase inhibitors HA1077 and Y27632 (3 mg/kg each) attenuated elevation of RVSP (22.0 +/- 3.7, 17.1 +/- 3.2, 14.3 +/- 2.6 mmHg, PE, PE+HA1077, PE+Y27632) and the severity of hypoxemia (66.3 +/- 16.2, 94.9 +/- 23.0, 89.1 +/- 8.5 Torr, PE, PE+HA1077, PE+Y27632) in the PE rats. These results suggest that pulmonary endothelial dysfunction and activation of Rho kinase may contribute to the potentiation of vasoconstriction and hypoxemia in the PE rats.
 ...
PMID:Involvement of Rho kinase in the pathogenesis of acute pulmonary embolism-induced polystyrene microspheres in rats. 1991 57

Acute pulmonary embolism (PE) is a severe and potentially fatal disease which acutely augments the right ventricle (RV) strain. Development of RV dysfunction (RVD) in the disease process is synonymous with an overall poor prognosis. The diagnosis of PE is usually established by a combination of clinical assessment, D-dimer test and medical imaging with either lung scintigraphy or pulmonary multidetector computer tomography (MDCT) angiography. Which of the two methods to use in PE diagnostic has not been determined and very limited data comparing these modalities are available. Assessment of RV function is cumbersome due to complex geometry. RVD is usually established by echocardiography which is observer dependent, has low reproducibility, and requires expertise. Therefore, a simple and reproducible biochemical method to assess RVD in patients with PE would be desirable. Brain natriuretic peptide (BNP), pro-atrial natriuretic peptide (pro-ANP), cardiac troponin I (TnI), and endothelin-1 (ET-1) have been the most studied plasma biomarkers in the context of risk stratification in PE. BNP is mainly produced in the ventricles of the heart. It is released from the left ventricle in response to increased filling pressure and is increased in chronic left heart failure. Pro-ANP is primarily produced in the atria, is released by atrial distention and is elevated in chronic pulmonary hypertension and could be an early marker for RVD. Plasma level of ET-1 has been shown to correlate with pulmonary pressure and is released from endothelial cells in the pulmonary vessels. Additionally, increases in circulating levels of ET-1 have been reported in an experimental animal model of PE. TnI is part of a complex of regulatory proteins in the cardiac myofilaments and is released upon myocyte injury. It is related to short term clinical outcome, prolonged hypotension, and cardiogenic shock after myocardial infarction and is a predictor of 30-day mortality and RVD using echocardiography in patients with PE. Our hypothesis was therefore that the neuroendocrine activation of BNP, pro-ANP, ET-1, and TnI alone or in combination could serve as markers of RVD in patients with PE. The use of plasma biomarkers would be much simpler than reproducible medical imaging methods such as magnetic resonance imaging (MRI), radionuclide based methods etc.
 ...
PMID:Neuroendocrine activation and diagnostics in pulmonary embolism: Translational studies. 2137 7