Enhanced levels of soluble and membrane-bound CD40 ligand in patients withunstable angina - Possible reflection of T lymphocyte and platelet involvement in the pathogenesis of acute coronary syndromes

Background-The CD40 ligand (CD40L) on activated T cells and platelets may b e activating matrix metalloproteinases, inducing procoagulant activity, and be involved in the pathogenesis of acute coronary syndromes by promoting p laque rupture in atheroma. Methods and Results-To study the role of CD40L-CD40 interaction in coronary disease, we analyzed levels of soluble (s) and membrane-bound CD40L in the peripheral blood from 29 patients with stable angina, 26 with unstable ang ina, and 19 controls. Our main findings follow. (1) Patients with unstable angina had significantly raised serum levels of sCD40L when compared with p atients with stable angina and controls. (2) Platelets could release large amounts of sCD40L when stimulated ex vivo with the thrombin receptor-agonis t peptide SFLLRN in both patients and controls. (3) Platelets in patients w ith unstable angina were characterized ex vivo by decreased intracellular l evels and decreased SFLLRN-stimulated release of sCD40L, which may possibly represent a higher percentage of degranulated platelets in these patients. (4) T cells in patients with unstable angina had enhanced surface expressi on of CD40L and increased release of sCD40L on anti-CD3/anti-CD28 stimulati on in vitro when compared with patients with stable angina and controls. (5 ) Recombinant CD40L and serum from patients with unstable angina who had hi gh sCD40L levels induced enhanced release of monocyte chemoattractant pepti de-1 from mononuclear cells, a CC-chemokine involved in the pathogenesis of atherosclerosis. Conclusions-This first demonstration of enhanced levels of soluble and memb rane-bound forms of CD40L in angina patients, with particularly high levels in patients with unstable angina, suggests that CD40L-CD40 interaction may play a pathogenic role in both the long-term atherosclerotic process and i n the triggering and propagation of acute coronary syndromes.