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Increased expression of neutrophil and monocyte adhesion molecules in unstable coronary artery disease
A Mazzone1, S De Servi, G Ricevuti
1Department of Internal Medicine and Therapeutics, IRCCS S Matteo Hospital, Pavia, Italy.
Insights
Patients with unstable angina show increased CD11b/CD18 receptors on leukocytes in coronary blood, suggesting an inflammatory response within the coronary tree. This may contribute to the pathogenesis of unstable coronary artery disease.
Area of Science:
- Cardiovascular Medicine
- Immunology
- Inflammation Research
Background:
- Leukocyte adhesion to endothelial cells is an early event in acute inflammation and vascular disease pathogenesis.
- The CD11/CD18 glycoprotein complex, particularly the CD11b/CD18 receptor, is crucial for leukocyte adhesion and can be upregulated by chemotactic factors.
- Understanding receptor expression during blood flow through the coronary tree is vital for ischemic heart disease research.
Purpose of the Study:
- To investigate the expression of CD11b/CD18 receptors on granulocytes and monocytes in the coronary tree of patients with ischemic heart disease.
- To determine if CD11b/CD18 receptor upregulation occurs during blood passage through coronary vessels in patients with clinical manifestations of ischemic heart disease.
Main Methods:
- Studied 39 patients undergoing coronary arteriography, categorized into unstable angina, stable exertional angina, and atypical chest pain groups.
- Collected simultaneous blood samples from the coronary sinus and aorta.
- Quantified cell surface CD11b/CD18 receptor expression on leukocytes using direct immunofluorescence and flow cytometry with monoclonal antibodies, without in vitro manipulation.
Main Results:
- Patients with unstable angina (Group 1) exhibited significantly higher CD11b/CD18 expression on granulocytes and monocytes in the coronary sinus compared to the aorta (P < .01).
- No significant difference in CD11b/CD18 expression was observed between the coronary sinus and aorta in patients with stable exertional angina (Group 2) or atypical chest pain (Group 3).
- Groups 1 and 2 had significant coronary artery disease, while Group 3 had normal coronary arteries.
Conclusions:
- Increased expression of CD11b/CD18 adhesion receptors on leukocytes in the coronary sinus of unstable angina patients indicates an active inflammatory process within the coronary tree.
- Leukocyte activation in unstable angina may contribute to coronary vasoconstriction, thrombosis, and platelet activation.
- These findings highlight the potential role of leukocyte-endothelial interactions in the pathogenesis of unstable coronary artery disease.
Background:
A rapid increase in leukocyte adhesion to endothelial cells is one of the first events in the acute inflammatory response and in the pathogenesis of vascular diseases. A subgroup of cell surface glycoproteins (the CD11/CD18 complex) play a major role in the leukocyte adhesion process; in particular, the CD11b/CD18 receptor can be upregulated severalfold in response to chemotactic factors. The purpose of this study was to assess whether upmodulation of granulocyte and monocyte CD11b/CD18 receptors takes place during the passage of blood through the coronary tree of patients with clinical manifestations of ischemic heart disease.
Methods And Results:
Thirty-nine patients who underwent diagnostic coronary arteriography were studied. Group 1 (15 patients) had a clinical diagnosis of unstable angina, group 2 (14 patients) had stable exertional angina, and group 3 (10 patients) had atypical chest pain. Simultaneous sampling from the coronary sinus and aorta was obtained before coronary arteriography. Cell surface receptors were detected by direct immunofluorescence evaluated by flow cytofluorimetry using monoclonal antibodies tagged with fluorescent markers. Leukocytes were stained in unseparated blood to avoid in vitro manipulation that could activate phagocytes. Group 1 and 2 patients had significant coronary artery disease (> 50% coronary narrowing in at least one major coronary vessel), whereas group 3 patients had normal coronary arteries. In group 1, granulocytes and monocytes showed a significantly higher expression of the CD11b/CD18 adhesion receptor in the coronary sinus than in the aorta (both P < .01), whereas no difference in CD11b/CD18 expression was seen in groups 2 and 3.
Conclusions:
Patients with unstable angina have an increased expression of granulocyte and monocyte CD11b/CD18 adhesion receptors, indicating that an inflammatory reaction takes place within their coronary tree. Activation of these leukocytes may induce coronary vasoconstriction, favor thrombotic processes, and further activate platelets, thus having potential implications on the pathogenesis of unstable coronary artery disease.