Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiopulmonary bypass is a planned support technique that results in a period of myocardial ischemia and reperfusion. In addition, it is associated with an inflammatory response likely involving endothelial cell activation. In previous studies, we showed that E-selectin and intercellular adhesion molecule-1 (ICAM-1) messenger ribonucleic acid (mRNA) are increased in human myocardium after cardiopulmonary bypass. We have now examined the expression of P-selectin mRNA by ribonuclease protection in paired atrial biopsy specimens from 12 patients before and after cardiopulmonary bypass. By means of immunocytochemistry, we have also examined the endothelial cell surface expression of P-selectin protein, as well as that of E-selectin and ICAM-1 in three additional patients. Patient ages ranged from 1 day to 8.5 years (median 12 months), and cardiopulmonary bypass times ranged from 46 to 196 minutes (median 144 minutes). By ribonuclease protection, there was marked variability in the expression of P-selectin in biopsy specimens before bypass. However, when compared with prebypass levels, P-selectin mRNA decreased modestly in 10 of 12 patients after bypass (median decrease 1.5-fold, p = 0.016). As seen with immunocytochemistry, P-selectin protein was distributed diffusely through the vascular bed on large vessels and small vessels before bypass but was virtually absent on capillaries in specimens taken after bypass. E-selectin, which was absent in prebypass biopsy specimens, was induced in one of the three specimens after bypass, but no change in ICAM-1 protein expression above baseline was noted. We also find that cultured human endothelial cells treated with tumor necrosis factor-alpha in doses which induce ICAM-1 mRNA simultaneously decrease their expression of P-selectin mRNA as compared with untreated cells. These observations suggest that endothelial P-selectin is transcriptionally downregulated after cardiopulmonary bypass at times when E-selectin and ICAM-1 are induced. Furthermore, we find that E-selectin and ICAM-1 are expressed at times and at sites where P-selectin is absent. Although it is possible that P-selectin may have been induced and lost at early times before reperfusion, these data suggest that endothelial P-selectin plays a limited role in the inflammatory response that ensues after cardiopulmonary bypass.
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PMID:P-selectin expression in myocardium of children undergoing cardiopulmonary bypass. 747 58

The aim of our study was to examine the mechanism of E-selectin production and leukocyte accumulation in myocardial ischaemia-reperfusion injury. Myocardial injury was induced in anaesthetized rats by the clamping of the left main coronary artery followed by reperfusion. After thoracotomy a silk suture was placed under the left coronary artery. The ligature was tied for a period of 1 h and after this period it was untied and the ischaemic myocardium was reperfused for 1 h (MI/R rats) or removed (SHAM MI/R rats). Myocardial ischaemia plus reperfusion in untreated rats decreased survival rate, produced a marked myocardial necrosis, enhanced cardiac myeloperoxidase activity (a marker enzyme commonly used to assess polymorphonuclear leukocyte infiltration) and increased serum creatinephosphokinase (CPK) activity, serum levels of tumour necrosis factor-alpha (TNF-alpha) and serum levels of soluble E-selectin (sE-selectin). Furthermore, MI/R rats had an increased pressure rate index studied as a quantitative means for assessing myocardial oxygen demand. Administration of cloricromene, an inhibitor of TNF-alpha, reduced TNF-alpha production, significantly lowered serum sE-selectin levels, blunted leukocyte accumulation in the ischaemic myocardium and protected the myocardium from injury due to ischaemia and reperfusion. The results of the present study show an involvement of E-selectin in vivo in the pathogenesis of myocardial ischaemia and reperfusion and suggest that TNF-alpha may induce in vivo the production of a specific adhesion mechanism which sustains leukocyte infiltration.
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PMID:Tumour necrosis factor mediates E-selectin production and leukocyte accumulation in myocardial ischaemia-reperfusion injury. 747 25

The role of E-selectin in the pathogenesis of an experimental model of myocardial ischemia-reperfusion injury was investigated. Pentobarbital anesthetized rats underwent left main coronary artery ligation (1 h) followed by reperfusion (1 h; MI/R). Sham operated rats were used as controls (sham MI/R). Myocardial ischemia-reperfusion injury reduced survival rate (50%), caused severe myocardial damage (necrotic area/area-at-risk 69.8 +/- 5%; necrotic area/total area = 56 +/- 7.6%), increased serum creatine phosphokinase activity (sham MI/R = 33 +/- 3 U/ml; MI/R = 215 +/- 13 U/ml), and elevated myeloperoxidase activity (investigated as an index of leukocyte adhesion and accumulation; sham MI/R = 0.11 +/- 0.02 U x 10(-3)/g tissue) in the area-at-risk (7.5 +/- 1.7 U x 10(-3)/g tissue) and in the necrotic area (7.8 +/- 2.2 U x 10(-3)/g tissue). Furthermore, MI/R rats had an increased pressure rate index, studied as a quantitative means for assessing myocardial oxygen demand. Administration of a hyperimmune serum containing antibodies against E-selectin significantly improved survival rate (80%), reduced myocardial injury (necrotic area/area-at-risk = 26.4 +/- 7%, P < 0.005; necrotic area/total area 19.1 +/- 2.8%, P < 0.005), lowered serum creatine phospokinase activity (85 +/- 5 U/ml, P < 0.001) and decreased myeloperoxidase activity in the area at risk (3.7 +/- 1.3 U x 10(-3)/g tissue, P < 0.001) and in the necrotic area (3.0 +/- 0.7 U x 10(-3)/g tissue). Finally, the administration of anti E-selectin antibodies improved the PRI in MI/R rats. The present data suggest that E-selectin in vivo plays a key role in the pathogenesis of myocardial ischemia/reperfusion injury.
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PMID:E-selectin in the pathogenesis of experimental myocardial ischemia-reperfusion injury. 751 8

Soluble adhesion molecules E-selectin, intercellular adhesion molecule (sICAM) and vascular cell adhesion molecule (sVCAM) were measured alongside von Willebrand factor (vWf) in 40 patients with peripheral vascular disease (PVD), 43 with ischaemic heart disease (IHD) and in equal numbers of age and sex matched asymptomatic controls. Increased vWf was found in patients with IHD (p = 0.0008) and in patients with PVD (p = 0.0001) relative to their respective controls but levels did not differ between the two patient groups. Raised sICAM was found in both PVD (p = 0.0003) and IHD (p = 0.0059) compared to their respective controls and was higher in PVD than in IHD (p = 0.0088). In the subjects taken as a whole, there was no correlation between vWf and sICAM. Levels of soluble E-selectin and sVCAM did not differ in patients or controls. These data suggest that soluble ICAM may be useful as an index of endothelial cell activation in clinical manifestations of atherosclerosis.
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PMID:Circulating endothelial cell/leukocyte adhesion molecules in atherosclerosis. 752 83

The time course of endothelial P-selectin, ICAM-1, and E-selectin expression was studied in a feline model of myocardial ischemia and reperfusion. Cats were subjected to 90 min of myocardial ischemia followed by 0, 10, 20, 60, 150, or 270 min of reperfusion. At the end of reperfusion, the coronary vasculature was examined immunohistochemically to localize monoclonal antibodies (mAbs) PB1.3, RR1/1, and Cy1787 directed against P-selectin, ICAM-1, and E-selectin, respectively. Immunohistochemical localization for P-selectin, recognized by mAb PB1.3, was maximally expressed 20 min after reperfusion in 60 +/- 6% of coronary venules (P < 0.05 compared to non-reperfused controls), and covered 59 +/- 3% of the endothelial cell perimeter of immunostained coronary venules. Immunolocalization of mAb PB1.3 gradually declined at 60, 150, and 270 min of reperfusion. Immunohistochemical localization of mAb RR1/1 (anti-ICAM-1) in endothelial cells of coronary venules was observed to a modest extent in non-ischemic myocardium and at 10, 20, and 60 min of reperfusion, but was significantly increased following 150 and 270 min of reperfusion (P < 0.05 compared non-reperfused controls). At 270 min post-reperfusion, mAb RR1/1 was seen in 50 +/- 4% of coronary venules. Endothelial immunolocalization of mAb Cy1787 (anti-E-selectin) was only observed in 13 +/- 1 and 14 +/- 3% of coronary venules after 150 and 270 min of reperfusion, respectively, suggesting that pronounced expression of E-selectin does not occur within 270 min after reperfusion. These results demonstrate sequential expression of three major endothelial cell adherence molecules in situ following myocardial ischemia and reperfusion. The timing of endothelial cell expressed P-selectin and ICAM-1 could coordinate neutrophil trafficking during the early stages of reperfusion.
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PMID:Time course of coronary vascular endothelial adhesion molecule expression during reperfusion of the ischemic feline myocardium. 753 Feb 83

Murine monoclonal antibody E9 recognises a transforming growth factor (TGF) beta receptor, which is expressed in increased amounts by activated endothelial cells. In order to examine the biological role of this molecule in atherosclerosis, we have measured levels of the TGF-beta receptor alongside those of two other endothelial cell products (von Willebrand factor and soluble E-selectin) in the serum of 55 patients with atherosclerosis (29 with ischaemic heart disease and 26 with peripheral vascular disease), and in a cohort of 26 age- and sex-matched asymptomatic controls. There were increased levels of the TGF-beta receptor (P = 0.0079) and von Willebrand factor (P = 0.0001), but not soluble E-selection in patients' serum relative to the controls. In multivariate analysis of the endothelial cell products against total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol, triglycerides, systolic and diastolic blood pressures, age, sex and smoking, both the TGF-beta receptor and von Willebrand factor correlated with total cholesterol (Spearman's r = 0.37 and r = 0.35, respectively, both P < 0.001). Lack of a correlation with a coarse endothelial damage marker von Willebrand factor or soluble E-selectin (produced by immunologically stimulated endothelial cells) implies other mechanisms are responsible for increased levels of the TGF-beta receptor in serum of patients with atherosclerosis.
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PMID:Serum levels of the TGF-beta receptor are increased in atherosclerosis. 864 63

It has been suggested that leukocyte adhesion mechanisms play a key role in experimental myocardial infarction. We have recently shown that E-selectin, an adhesion molecule belonging to the selectin family, is involved in the pathogenesis of experimental myocardial ischemia. We investigated the circulating levels of E-selectin, studied as a marker of endothelial dysfunction, in acute myocardial infarction. Our study was carried out in 60 patients, 20 hospitalized for acute myocardial infarction, 20 suffered from angina pectoris and 20 healthy control subjects. Patients with acute myocardial infarction had increased serum levels of soluble E-selectin (sE-selectin = 255 +/- 12 ng/ml) compared to both patients with angina pectoris (sE-selectin = 51 +/- 14 ng/ml). Thrombolytic therapy with urokinase (1,000,000 IU as an intravenous bolus in 5 min, followed by producing reperfusion and reduced the serum levels of sE-selectin (71 +/- 19 ng/ml). Our results confirm previous experimental data and indicate that adhesion mechanisms supporting leukocyte-endothelium interaction may also be operative in human acute myocardial infarction.
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PMID:Soluble E-selectin levels in acute human myocardial infarction. 865 56

Increased levels of the endothelial markers soluble E-selectin (P = 0.011), soluble thrombomodulin (P < 0.0001) and von Willebrand factor (VWF, P < 0.0001) were found in 116 patients with ischaemic heart disease compared to an equal number of age- and sex-matched asymptomatic controls. In a multivariate analysis of the markers versus the major risk factors for atherosclerosis, VWF correlated with total cholesterol (P = 0.002) and E-selectin with sex (lower in women, P = 0.004) and triglycerides (P = 0.007). The data point to profound differences in the release mechanisms of these three endothelial cell products and suggests that further studies into the roles of these molecules in coronary artery disease are warranted.
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PMID:Circulating endothelial cell/leucocyte adhesion molecules in ischaemic heart disease. 890 79

Endothelial cell dysfunction is likely to be important in the pathophysiology of ischaemic heart disease and increased levels of endothelial cell markers soluble E-selectin and soluble thrombomodulin may reflect this damage. To determine whether increased levels of these markers were predictive of disease progression, we obtained plasma from 54 patients who had survived a myocardial infarction. Soluble E-selectin and soluble thrombomodulin were measured by ELISA. After 49 months, 24 patients had suffered an additional cardiovascular event such as a second myocardial infarction or requirement for arterial surgery. Soluble E-selectin was 60+/-30 ng/mL in patients who suffered an end-point and was 54+/-23 ng/mL in those without an end-point (p=0.43). Soluble thrombomodulin was 65+/-24 ng/mL in patients who suffered an end-point and was 49+/-19 ng/mL in patients who were free of an end-point (p=0.009). The major risk factors for atherosclerosis (hypercholesterolaemia, hypertension, smoking) or peak creatinine kinase levels were unable to predict the development of an end-point. Using life tables, soluble thrombomodulin had a significant effect on survival free of an end-point (p=0.011). We conclude that the measurement of soluble E-selectin is of limited value in epidemiological studies, and that raised soluble thrombomodulin is a new marker for the progression of atherosclerosis in patients with ischaemic heart disease.
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PMID:Prognostic value of increased soluble thrombomodulin and increased soluble E-selectin in ischaemic heart disease. 929 60

Previous studies have shown that adhesion molecules play a crucial role in leukocyte-endothelium interactions that occur during myocardial ischemia and reperfusion. We assessed the plasma levels of the soluble form of E-selectin (sE-selectin) and intercellular adhesion molecule-1 (sICAM-1) in 15 patients with acute myocardial infarction (AMI) and in 15 controls with chronic stable angina. In patients with AMI, the levels of sE-selectin and sICAM-1 increased significantly during the first 8 h after infarction and subsequently decreased. Soluble E-selectin levels were inversely related to the peak plasma levels of creatine kinase-MB (CK-MB), and the time course of their appearance in plasma correlated with that of neutrophil count and plasma D-dimer. In individual patients, peak and mean sICAM-1 levels correlated respectively with plasma D-dimer concentrations and monocyte count, but no correlation were found when their time courses were analyzed. Eight hours after symptom onset, the mean plasma sE-selectin levels were higher in patients with AMI than in those with stable angina, whereas no significant differences were found in mean plasma sICAM-1 levels between the two groups at every time analyzed. In the acute phase of MI (a) sE-selectin and sICAM-1 levels increase during the first 8 h and subsequently decrease; (b) the increase in sE-selectin probably reflects activation of endothelial cells, correlates with other inflammatory and coagulation parameters, and is inversely related to the degree of myocardial damage; and (c) sICAM-1 plasma levels do not represent a good marker of "cell activation" because they reflect activation of different cells and may be affected by different conditions.
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PMID:Soluble E-selectin and intercellular adhesion molecule-1 plasma levels increase during acute myocardial infarction. 933 4


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