Increased granzyme B production from peripheral blood mononuclear cells in patients with acute coronary syndrome.

OBJECTIVES

To clarify the role of granzyme B in acute coronary syndrome.

DESIGN AND

SETTING

Granzyme B is a member of the serine esterase family released from cytotoxic lymphocytes and plays an important role in cellular apoptosis by activating intracellular caspases. Granzyme B expression was compared between patients with stable and unstable angina pectoris (UAP).

PATIENTS: 173 patients with coronary artery disease (CAD) were enrolled. 84 patients were found to have stable angina pectoris (SAP) and 89 patients to have UAP.

METHODS

Peripheral blood was drawn from the patients. Peripheral blood mononuclear cells (PBMCs) isolated by gradient centrifugation were cultured at a density of 2x106 cells/ml for 24 hours. The supernatants were collected 24 hours after incubation and the granzyme B level was measured by enzyme-linked immunosorbent assay. Polychromic flow cytometric analysis was performed to evaluate the expression of granzyme B in the cells.

RESULTS

Granzyme B production from PBMCs of UAP patients was significantly higher than from those of patients with SAP (39.1 (SEM 6.6) versus 17.0 (SEM 1.8) pg/ml, p<0.05). Granzyme B production from PBMCs increased with the increasing TIMI risk score in UAP patients. The percentage of granzyme B-positive lymphocytes to CD3-positive lymphocytes in UAP patients was significantly higher than in SAP (32.1% (SEM 1.6%) versus 18.4% (SEM 0.9%), p<0.01).

CONCLUSIONS

These results suggest that granzyme B might play an important role in triggering acute coronary events by inducing apoptosis and the degradation of atherosclerotic coronary plaques.