Association between Microalbuminuria Predicting In-Stent Restenosis after Myocardial Infarction and Cellular Senescence of Endothelial Progenitor Cells

作者：Ota Hisanobu; Takehara Naofumi^*; Aonuma Tatsuya; Kabara Maki; Matsuki Motoki; Yamauchi Atsushi; Takeuchi Toshiharu; Kawabe Jun ichi; Hasebe Naoyuki

来源：PLos One, 2015, 10(4): e0123733.

DOI：10.1371/journal.pone.0123733

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-beta-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-beta-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.

• 出版日期2015-4-13