title: Incidence and Expression of Circulating Cell Free p53-Related Genes in Acute Myocardial Infarction Patients.
abstract: OBJECTIVE
  The circulating RNA levels are predictive markers in several diseases. We determined the levels of circulating p53-related genes in patients with acute ST-segment elevation myocardial infarction (STEMI), indicating major heart muscle damage.
  
  
  METHODS
  Plasma RNA was extracted from the patients (n=45) upon their arrival to the hospital (STEMI 0h) and at four hours post-catheterization (STEMI 4h) as well as from controls (n=34).
  
  
  RESULTS
  Of 18 circulating p53-related genes, nine genes were detectable. A significantly lower incidence of circulating p21 (p ＜ 0.0001), Notch1 (p=0.042) and BTG2 (p ＜ 0.0001) was observed in the STEMI 0h samples in comparison to the STEMI 4h and control samples. Lower expression levels (2.1-fold) of circulating BNIP3L (p=0.011), p21 (3.4-fold, p=0.005) and BTG2 (6.3-fold, p=0.0001) were observed in the STEMI 0h samples in comparison to the STEMI 4h samples, with a 7.4-fold lower BTG2 expression (p ＜ 0.001) and 2.6-fold lower p21 expression (p=0.034) compared to the control samples. Moreover, the BNIP3L expression (borderline significance, p=0.0655) predicted the level of peak troponin, a marker of myocardial infarction. In addition, the BNIP3L levels on admission (p=0.0025), at post-catheterization (p=0.020) and the change between the groups (p=0.0079) were inversely associated with troponin. The BNIP3L (p=0.0139) and p21 levels (p=0.0447) were also associated with a longer time to catheterization.
  
  
  CONCLUSIONS
  Our results suggest that circulating downstream targets of p53 are inhibited during severe AMI and subsequently re-expressed after catheterization, uncovering possible novel death-or-survival decisions regarding the fate of p53 in the heart and the potential use of its target genes as prognostic biomarkers for oxygenation normalization.
authors.affiliation: Division of Cardiology, Meir Medical Center.
authors.forename: David
authors.initials: D
authors.lastname: Pereg
authors.forename: Keren
authors.initials: K
authors.lastname: Cohen
authors.forename: Morris
authors.initials: M
authors.lastname: Mosseri
authors.forename: Tatiana
authors.initials: T
authors.lastname: Berlin
authors.forename: David M
authors.initials: DM
authors.lastname: Steinberg
authors.forename: Martin
authors.initials: M
authors.lastname: Ellis
authors.forename: Osnat
authors.initials: O
authors.lastname: Ashur-Fabian
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000097:blood / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016158:Genes, p53; D006801:Humans; D017874:Immediate-Early Proteins / Q000097:blood / Q000235:genetics; D015994:Incidence; D008297:Male; D008565:Membrane Proteins / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000453:epidemiology / Q000235:genetics*; D010100:Oxygen / Q000737:chemistry; D062645:Percutaneous Coronary Intervention; D010477:Perfusion; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000097:blood / Q000235:genetics; D012313:RNA / Q000097:blood*; D051881:Receptor, Notch1 / Q000097:blood / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000097:blood / Q000235:genetics
chemical_list: C116838:BNIP3L protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D017874:Immediate-Early Proteins; D008565:Membrane Proteins; C497761:NOTCH1 protein, human; D011518:Proto-Oncogene Proteins; D051881:Receptor, Notch1; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C070114:BTG2 protein, human; D012313:RNA; D010100:Oxygen