title: Role of cathepsin D activation in major adverse cardiovascular events and new-onset heart failure after STEMI.
abstract: OBJECTIVE
  Increased serum levels of the activated aspartic lysosomal endopeptidase cathepsin D (CatD) have been found in patients with acute myocardial infarction (AMI). However, to date there have been no analyses of clinical follow-up data measuring the enzyme course and its role in the development of post-MI heart failure. This study aimed to evaluate the role of serum CatD activity in the development of heart failure in patients with ST-segment elevation acute myocardial infarction (STEMI).
  
  
  METHODS
  Eighty-eight consecutive patients (79.5 % men, mean age 57.4 ± 10.2 years) with STEMI were included in this study. Serum CatD activity was measured directly after primary percutaneous coronary intervention (PCI), before discharge, and at the 6-month follow-up. Patients were monitored for major adverse cardiovascular events (MACE), defined as hospitalization due to cardiovascular causes, recurrent nonfatal myocardial infarction, unplanned PCI, new-onset heart failure, and cardiovascular mortality.
  
  
  RESULTS
  Serum CatD activity was significantly higher in patients with AMI after PCI and during follow-up (FU) than that in age-matched controls (16.2 ± 7.5 and 29.8 ± 8.9 vs. 8.5 ± 4.2 RFU; p < 0.001 for each time point). At the 6-month follow-up, serum CatD activity in these patients was inversely related to new-onset cardiac dysfunction compared with patients with preserved and improved LVEF after treatment (23.1 ± 3.2 vs. 28.8 ± 7.0 and 29.7 ± 5.0 RFU respectively, p < 0.01). Patients suffering from MACE during a follow-up period of 6 months had lower serum levels of activated CatD than those without any MACE (23.8 ± 4.6 vs 29.6 ± 6.9 RFU; p < 0.001).
  
  
  CONCLUSIONS
  Serum CatD activity as a marker of healthy endogenous phagocytosis and remodeling was impaired in patients with new-onset cardiac dysfunction, and lower levels of serum CatD were associated with MACE at the 6-month post-MI follow-up.
authors.affiliation: Faculty of Medicine, Department of Cardiology, BezmiÂlem Foundation University, Adnan Menderes Avenue, Vatan Street, 34093, Fatih/Istanbul, Turkey. haticeyamac80@yahoo.de.
authors.forename: Aylin Hatice
authors.initials: AH
authors.lastname: Yamac
authors.affiliation: Faculty of Medicine, Department of Cardiology, BezmiÂlem Foundation University, Adnan Menderes Avenue, Vatan Street, 34093, Fatih/Istanbul, Turkey.
authors.forename: Emrah
authors.initials: E
authors.lastname: Sevgili
authors.affiliation: Faculty of Medicine, Department of Cardiology, BezmiÂlem Foundation University, Adnan Menderes Avenue, Vatan Street, 34093, Fatih/Istanbul, Turkey.
authors.forename: Sitki
authors.initials: S
authors.lastname: Kucukbuzcu
authors.affiliation: Faculty of Medicine, Department of Cardiology, BezmiÂlem Foundation University, Adnan Menderes Avenue, Vatan Street, 34093, Fatih/Istanbul, Turkey.
authors.forename: Muharrem
authors.initials: M
authors.lastname: Nasifov
authors.affiliation: Faculty of Medicine, Department of Cardiology, BezmiÂlem Foundation University, Adnan Menderes Avenue, Vatan Street, 34093, Fatih/Istanbul, Turkey.
authors.forename: Ziya
authors.initials: Z
authors.lastname: Ismailoglu
authors.affiliation: Faculty of Medicine, Department of Biochemistry, BezmiÂlem Foundation University, Istanbul, Turkey.
authors.forename: Elif
authors.initials: E
authors.lastname: Kilic
authors.affiliation: Faculty of Medicine, Department of Medical Biology, BezmiÂlem Foundation University, Istanbul, Turkey.
authors.forename: Cilem
authors.initials: C
authors.lastname: Ercan
authors.affiliation: Faculty of Medicine, Department of Cardiology, BezmiÂlem Foundation University, Adnan Menderes Avenue, Vatan Street, 34093, Fatih/Istanbul, Turkey.
authors.forename: Parviz
authors.initials: P
authors.lastname: Jafarov
authors.affiliation: Faculty of Medicine, Department of Cardiology, BezmiÂlem Foundation University, Adnan Menderes Avenue, Vatan Street, 34093, Fatih/Istanbul, Turkey.
authors.forename: Hüseyin
authors.initials: H
authors.lastname: Uyarel
authors.affiliation: Faculty of Medicine, Department of Cardiology, BezmiÂlem Foundation University, Adnan Menderes Avenue, Vatan Street, 34093, Fatih/Istanbul, Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Bacaksiz
mesh_terms: D015415:Biomarkers / Q000097:blood; D002402:Cathepsin D / Q000097:blood*; D015984:Causality; D015897:Comorbidity; D016757:Death, Sudden, Cardiac / Q000453:epidemiology; D004789:Enzyme Activation; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000401:mortality* / Q000517:prevention & control; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000401:mortality / Q000601:surgery*; D062645:Percutaneous Coronary Intervention / Q000401:mortality*; D011379:Prognosis; D012008:Recurrence; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity; D015996:Survival Rate; D014421:Turkey / Q000453:epidemiology
chemical_list: D015415:Biomarkers; C533922:CTSD protein, human; D002402:Cathepsin D
keywords: Cardiac remodeling; Heart failure; Myocardial infarction; Percutaneous coronary intervention; Serum cathepsin D activity