Abstract 12809: Microalbuminuria Associated with Functionally Impaired Endothelial Progenitor Cells Predicts In-Stent Late Loss via Cellular Senescence after Myocardial Infarction
Introduction: Microalbuminuria in patients with acute myocardial infarction (AMI) is well known to be associated with an increased risk of cardiovascular events and mortality. However, the underlying pathophysiological mechanism remains unclear. We assessed the hypothesis that patients with microalbuminuria after AMI have functional disorders of endothelial progenitor cells (EPCs) associated with adverse coronary outcome.
Methods: Forty-five consecutive AMI patients, who underwent percutaneous coronary intervention (PCI), were divided into two groups by urinary albumin excretion ratio: normal albuminuria group (NRM; <30mg/day, n = 24) and microalbuminuria group (ALB; ≥30mg/day, n = 21). At 2nd and 7th day after AMI, circulating EPCs (CD34/Flk1-positive cells) were counted and cultured-EPCs were generated from peripheral blood mononuclear cells (MNC). To evaluate adhesion ability and cellular senescence of cultured-EPCs, the numbers of lectin-acLDL-positive cells and SA-beta galactosidase-positive cells were counted by immunohistochemistry. The expression level of mRNA of Sirtuin1 in cultured-EPCs was measured by qRT-PCR. Angiographic in-stent late loss in PCI lesions of patients who were implanted bare-metal stents was evaluated at the 6-month after PCI.
Results: Although the numbers of circulating EPCs were significantly increased in ALB at day7, increased adhesion ability of EPCs was not observed in ALB from day2 to day7 (9.4% to 9.0%: lectin-acLDL positive EPCs per MNCs, p = 0.55), which was observed in NRM (9.1% to 13.3%, p<0.05). Meanwhile, the large numbers of SA-beta galactosidase-positive cells in cultured-EPCs were observed in ALB compared with NRM (ALB, 63.4%; NRM, 28.9%; p<0.001) and mRNA level of Sirtuin1 in cultured-EPCs was significantly lower in ALB (ALB, 2.42 ± 0.86 fold; NRM, 7.10 ± 1.91 fold; p<0.05) compared with NRM at day7. At 6-month after AMI, in-stent late loss was significantly higher in ALB (ALB, 1.14 ± 0.16 mm; NRM, 0.75 ± 0.09 mm, p<0.05).
Conclusions: These findings suggest that the functional disorder of EPCs, is accompanied by cellular senescence via impairment of Sirtuin1 gene expression, and is closely associated with microalbuminuria after AMI, and may aggravate coronary remodeling.
- © 2012 by American Heart Association, Inc.