title: Enhanced levels of soluble and membrane-bound CD40 ligand in patients with unstable angina. Possible reflection of T lymphocyte and platelet involvement in the pathogenesis of acute coronary syndromes.
abstract: BACKGROUND
  The CD40 ligand (CD40L) on activated T cells and platelets may be activating matrix metalloproteinases, inducing procoagulant activity, and be involved in the pathogenesis of acute coronary syndromes by promoting plaque rupture in atheroma.
  
  
  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 angina, and 19 controls. Our main findings follow. (1) Patients with unstable angina had significantly raised serum levels of sCD40L when compared with patients with stable angina and controls. (2) Platelets could release large amounts of sCD40L when stimulated ex vivo with the thrombin receptor-agonist peptide SFLLRN in both patients and controls. (3) Platelets in patients with unstable angina were characterized ex vivo by decreased intracellular levels 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 expression of CD40L and increased release of sCD40L on anti-CD3/anti-CD28 stimulation in vitro when compared with patients with stable angina and controls. (5) Recombinant CD40L and serum from patients with unstable angina who had high sCD40L levels induced enhanced release of monocyte chemoattractant peptide-1 from mononuclear cells, a CC-chemokine involved in the pathogenesis of atherosclerosis.
  
  
  CONCLUSIONS
  This first demonstration of enhanced levels of soluble and membrane-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 in the triggering and propagation of acute coronary syndromes.
authors.affiliation: Section of Clinical Immunology and Infectious Diseases, Research Institute for Internal Medicine, Department of Cardiology, University of Oslo, Norway.
authors.forename: P
authors.initials: P
authors.lastname: Aukrust
authors.forename: F
authors.initials: F
authors.lastname: Müller
authors.forename: T
authors.initials: T
authors.lastname: Ueland
authors.forename: T
authors.initials: T
authors.lastname: Berget
authors.forename: E
authors.initials: E
authors.lastname: Aaser
authors.forename: A
authors.initials: A
authors.lastname: Brunsvig
authors.forename: N O
authors.initials: NO
authors.lastname: Solum
authors.forename: K
authors.initials: K
authors.lastname: Forfang
authors.forename: S S
authors.initials: SS
authors.lastname: Frøland
authors.forename: L
authors.initials: L
authors.lastname: Gullestad
mesh_terms: D000208:Acute Disease; D000368:Aged; D000787:Angina Pectoris / Q000097:blood / Q000276:immunology; D000789:Angina, Unstable / Q000097:blood / Q000453:epidemiology / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D019013:CD40 Antigens / Q000502:physiology; D023201:CD40 Ligand; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D002317:Cardiovascular Agents / Q000627:therapeutic use; D002462:Cell Membrane / Q000737:chemistry; D018932:Chemokine CCL2 / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D003327:Coronary Disease / Q000209:etiology* / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis*; D008666:Metalloendopeptidases / Q000096:biosynthesis; D008875:Middle Aged; D010446:Peptide Fragments / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects; D012422:Rupture, Spontaneous; D012907:Smoking / Q000453:epidemiology; D012995:Solubility; D013577:Syndrome; D014280:Triglycerides / Q000097:blood; D014657:Vasculitis / Q000150:complications / Q000378:metabolism
chemical_list: D019013:CD40 Antigens; D002317:Cardiovascular Agents; D018932:Chemokine CCL2; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D014280:Triglycerides; C082835:thrombin receptor peptide (42-47); D023201:CD40 Ligand; D002784:Cholesterol; D008666:Metalloendopeptidases