title: Association between microalbuminuria predicting in-stent restenosis after myocardial infarction and cellular senescence of endothelial progenitor cells.
abstract: OBJECTIVE
  Relationship between microalbuminuria and worse outcome of coronary artery disease patients is discussed, but its underlying pathophysiological mechanism remains unclear. We investigated the role of microalbuminuria to the function of endothelial progenitor cells (EPCs), that might affect to outcome of acute myocardial infarction (AMI) patients.
  
  
  METHODS
  Forty-five AMI patients were divided into two groups according to their urinary albumin excretion: normal (n = 24) and microalbuminuria (>30 mg/day, n = 21). At day-2 and day-7 after AMI onset, circulating-EPCs (CD34+ Flk1+) were quantified by flow cytometry. The number of lectin-acLDL-positive cultured-EPCs immobilized on fibronectin was determined. To assess the cellular senescence of cultured-EPCs, the expression level of sirtuin-1 mRNA and the number of SA-β-gal positive cell were evaluated. Angiographic late in-stent loss after percutaneous coronary intervention (PCI) was evaluated at a six-month follow-up.
  
  
  RESULTS
  No significant differences in coronary risk and the extent of myocardial damage were observed between the two groups. Late in-stent loss at the six-month follow-up was significantly higher in the microalbuminuria group (normal:microalbuminuria = 0.76±0.34:1.18±0.57 mm, p=0.021). The number of circulating-EPCs was significantly increased in microalbuminuria group at day-7, however, improved adhesion of EPCs was observed in normal group but not in microalbuminuria group from baseline to day-7 (+3.1±8.3:-1.3±4.4%: p<0.05). On the other hand, in microalbuminuria group at day-7, the level of sirtuin-1 mRNA expression of cultured-EPCs was significantly decreased (7.1±8.9:2.5±3.7 fold, p<0.05), which was based on the negative correlation between the level of sirtuin-1 mRNA expression and the extent of microalbuminuria. The ratio of SA-β-gal-positive cells in microalbuminuria group was increased compared to that of normal group.
  
  
  CONCLUSIONS
  Microalbuminuria in AMI patients is closely associated with functional disorder of EPCs via cellular senescence, that predicts the aggravation of coronary remodeling after PCI.
authors: Department of Internal Medicine, Division of Cardiology, Nephrology, Pulmonology and Neurology, Asahikawa Medical University (AMU), Asahikawa, Japan.
authors: Hisanobu
authors: H
authors: Ota
authors: Department of Cardiovascular Regeneration and Innovation, Asahikawa Medical University (AMU), Asahikawa, Japan.
authors: Naofumi
authors: N
authors: Takehara
authors: Department of Internal Medicine, Division of Cardiology, Nephrology, Pulmonology and Neurology, Asahikawa Medical University (AMU), Asahikawa, Japan.
authors: Tatsuya
authors: T
authors: Aonuma
authors: Department of Cardiovascular Regeneration and Innovation, Asahikawa Medical University (AMU), Asahikawa, Japan.
authors: Maki
authors: M
authors: Kabara
authors: Department of Internal Medicine, Division of Cardiology, Nephrology, Pulmonology and Neurology, Asahikawa Medical University (AMU), Asahikawa, Japan.
authors: Motoki
authors: M
authors: Matsuki
authors: Department of Internal Medicine, Division of Cardiology, Nephrology, Pulmonology and Neurology, Asahikawa Medical University (AMU), Asahikawa, Japan.
authors: Atsushi
authors: A
authors: Yamauchi
authors: Department of Internal Medicine, Division of Cardiology, Nephrology, Pulmonology and Neurology, Asahikawa Medical University (AMU), Asahikawa, Japan.
authors: Toshiharu
authors: T
authors: Takeuchi
authors: Department of Cardiovascular Regeneration and Innovation, Asahikawa Medical University (AMU), Asahikawa, Japan.
authors: Jun-ichi
authors: J
authors: Kawabe
authors: Department of Internal Medicine, Division of Cardiology, Nephrology, Pulmonology and Neurology, Asahikawa Medical University (AMU), Asahikawa, Japan.
authors: Naoyuki
authors: N
authors: Hasebe
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000419:Albuminuria / Q000150:complications* / Q000175:diagnosis*; D000792:Angiography; D018952:Antigens, CD34 / Q000378:metabolism; D016922:Cellular Senescence; D023903:Coronary Restenosis / Q000150:complications* / Q000175:diagnosis*; D066026:Endothelial Progenitor Cells / Q000166:cytology*; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005919:Glomerular Filtration Rate; D006801:Humans; D037102:Lectins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications / Q000601:surgery*; D012307:Risk Factors; D056564:Sirtuin 1 / Q000378:metabolism; D015607:Stents; D016896:Treatment Outcome
chemical_list: D018952:Antigens, CD34; D005353:Fibronectins; D037102:Lectins; D056564:Sirtuin 1