title: Platelet expression of transforming growth factor beta 1 is enhanced and associated with cardiovascular prognosis in patients with acute coronary syndrome.
abstract: BACKGROUND
  Functional recovery and prognosis after acute coronary syndromes (ACS) are mainly driven by the extent of reperfusion injury and myocardial repair mechanisms. Transforming growth factor-beta 1 (TGF-β1) is critically involved in cardiac injury, repair and remodeling. In this study, we investigated the prognostic role of platelet TGF-β1 surface expression and circulating TGF-β1 levels in patients with coronary artery disease (CAD).
  
  
  RESULTS
  Expression of TGF-β1 in platelets and circulating TGF-β1 levels were investigated by flow cytometry and ELISA, respectively, among patients with ACS and stable CAD undergoing percutaneous coronary intervention (PCI). In a cohort study, platelet and circulating TGF-β1 was measured in 299 patients with symptomatic CAD (stable CAD = 145, ACS = 154) at the time of PCI. The primary combined endpoint was defined as death and/or STEMI during 12-month follow-up. Platelets expressed TGF-β1 and circulating TGF-β1 showed a weak, but significant negative correlation. TGF-β1 surface expression was significantly elevated on platelets in ACS patients compared to patients with stable CAD (median MFI 13.4 vs. median MFI 11.7, p = 0.003). During follow-up, lower platelet expression of TGF-β1 was associated with all-cause mortality (median MFI 11.0 vs. median MFI 13.9, p = 0.011) as well as for the combined endpoint of death and/or STEMI, (median MFI 10.8 vs. median MFI 13.9, p = 0.006). In multivariate analysis platelet TGF-β1 expression was independently associated with the combined primary endpoint in the overall cohort (Hazard Ratio 0.31, 95% Confidence Interval 0.11-0.89, p = 0.029) and was strongly associated with prognosis in ACS patients. There was no significant association of circulating TGF-β1 levels neither with the presence of ACS nor the occurrence of the primary endpoint.
  
  
  CONCLUSIONS
  These findings highlight a potential role of platelet expressed TGF-β1 in ACS and indicate a prognostic value of TGF-β1 on clinical outcomes in patients with acute coronary syndromes. Large scale studies are warranted to further evaluate the regulatory mechanisms of platelet TGF-β1 expression- and its prognostic impact in CAD.
authors.affiliation: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Universität Tübingen, Tübingen, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Rath
authors.affiliation: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Universität Tübingen, Tübingen, Germany.
authors.forename: Madhumita
authors.initials: M
authors.lastname: Chatterjee
authors.affiliation: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Universität Tübingen, Tübingen, Germany.
authors.forename: Iris
authors.initials: I
authors.lastname: Müller
authors.affiliation: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Universität Tübingen, Tübingen, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Müller
authors.affiliation: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Universität Tübingen, Tübingen, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Böckmann
authors.affiliation: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Universität Tübingen, Tübingen, Germany.
authors.forename: Michal
authors.initials: M
authors.lastname: Droppa
authors.affiliation: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Universität Tübingen, Tübingen, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Stimpfle
authors.affiliation: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Universität Tübingen, Tübingen, Germany.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Karathanos
authors.affiliation: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Universität Tübingen, Tübingen, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Borst
authors.affiliation: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Universität Tübingen, Tübingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Seizer
authors.affiliation: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Universität Tübingen, Tübingen, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Langer
authors.affiliation: Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany; Department of Clinical Pharmacology, University Hospital of Tübingen, Tübingen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schwab
authors.affiliation: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Universität Tübingen, Tübingen, Germany. Electronic address: meinrad.gawaz@med.uni-tuebingen.de.
authors.forename: Meinrad
authors.initials: M
authors.lastname: Gawaz
authors.affiliation: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Universität Tübingen, Tübingen, Germany. Electronic address: tobias.geisler@med.uni-tuebingen.de.
authors.forename: Tobias
authors.initials: T
authors.lastname: Geisler
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood*; D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000166:cytology* / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood*; D002462:Cell Membrane / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D053773:Transforming Growth Factor beta1 / Q000097:blood* / Q000378:metabolism
chemical_list: D053773:Transforming Growth Factor beta1
keywords: Acute coronary syndrome; Coronary artery disease; Platelets; Transforming growth factor beta-1