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Thrombolytic therapy with urokinase reduces increased circulating endothelial adhesion molecules in acute myocardial
F Squadrito1, A Saitta, D Altavilla
1Institute of Pharmacology, University of Messina, Italy.
Insights
This study found elevated levels of soluble E-selectin and ICAM-1 in acute myocardial infarction patients. Thrombolytic therapy significantly reduced these adhesion molecules, unlike conventional treatment.
Area of Science:
- Cardiology
- Immunology
- Biochemistry
Background:
- Acute myocardial infarction (AMI) involves complex inflammatory processes.
- Adhesion molecules like E-selectin and ICAM-1 play a role in leukocyte-endothelium interactions during inflammation.
Purpose of the Study:
- To investigate serum levels of E-selectin and ICAM-1 in patients with AMI.
- To compare these levels with chronic stable angina patients and healthy controls.
- To evaluate the effect of thrombolytic therapy versus conventional therapy on these markers.
Main Methods:
- Serum samples were collected from 80 patients (40 AMI, 20 chronic angina, 20 controls) at various time points.
- Quantification of soluble E-selectin (sE-selectin), soluble ICAM-1 (sICAM-1), and TNF-alpha using specific immunoassays.
- Creatinine kinase (CK) levels were measured to assess myocardial damage.
Main Results:
- AMI patients exhibited significantly higher serum levels of sE-selectin and sICAM-1 compared to controls and angina patients.
- Tumor Necrosis Factor-alpha (TNF-alpha) levels were also elevated in AMI patients.
- Thrombolytic therapy with urokinase led to a significant reduction in sE-selectin and sICAM-1 levels.
- Conventional nitroglycerin therapy did not result in a significant reduction of these adhesion molecules.
Conclusions:
- Elevated circulating E-selectin and ICAM-1 are associated with acute myocardial infarction in humans.
- Leukocyte-endothelium adhesion mechanisms are implicated in the pathophysiology of AMI.
- Successful thrombolytic therapy can modulate these inflammatory markers, suggesting a potential therapeutic benefit.
Abstract:
The aim was to investigate circulating E-selectin and Intercellular Adhesion Molecule-1 (ICAM-1) in acute myocardial infarction. Our study was carried out in 80 patients, 40 hospitalized for acute myocardial infarction (AMI), 20 suffering from chronic stable angina and 20 healthy control subjects. Samples of venous blood were taken from all patients at the moment of hospitalization and after 2, 4, 6, 8, 10, 12 and 24 hours from the thrombolytic treatment (AMI + urokinase) or conventional therapy (AMI + nitroglycerin), for the dosage of creatinine kinase (CK) and adhesion molecules. The CK was determined by means of a Hitachi 901 automatic analyser using an enzymatic method (reagents Boheringer-Biochemia, Germany). Soluble E-selectin (sE-selectin) and soluble ICAM-1 (sICAM-1) were measured in the serum using a specific immunoassay (British Biotechnology Products). The serum levels of Tumor Necrosis Factor (TNF-alpha) were evaluated using an immunoenzymatic assay to quantitate the serum levels of the cytokine (British Biotechnology Products). Patients with acute myocardial infarction (AMI) had increased serum levels of soluble E-selectin (sE-selectin; AMI + urokinase = 312 +/- 20 ng/ml; AMI + nitroglycerin = 334 +/- 15 ng/ml) and soluble ICAM-1 (sICAM-1; AMI + urokinase = 629 +/- 30 ng/ml; AMI + nitroglycerin = 655 +/- 25 ng/ml) compared to both patients with chronic angina (sE-selectin = 67 +/- 10 ng/ml; sICAM-1 = 230 +/- 20 ng/ml) and healthy control subjects (sE-selectin = 53 +/- 15 ng/ml; sICAM-1 200 +/- 16 ng/ml). Furthermore patients with acute myocardial infarction also had increased serum levels of Tumor Necrosis Factor (TNF-alpha = 309 +/- 10 pg/ml; control subjects = 13 +/- 5 pg/ml). Thrombolytic therapy with urokinase (1,000,000 IU as an intravenous bolus for 5 minutes, followed by an infusion of an additional 1,000,000 IU for the following two hours) succeeded in producing reperfusion and reduced the serum levels of sE-selectin (52 +/- 13 ng/ml) and sICAM-1 (202 +/- 31 ng/ml). In contrast patients not eligible for thrombolytic therapy and therefore treated with conventional therapy (a continuous i.v. infusion of nitroglycerin at the dose of 50 mg/die) did not show any significant reduction in both sE-selectin and sICAM-1 throughout the study. Our results confirm previous experimental data and indicate that adhesion mechanisms supporting leukocyte-endothelium interaction may also be operative in human acute myocardial infarction.