Ota Hisanobu, Takehara Naofumi, Aonuma Tatsuya, Kabara Maki, Matsuki Motoki, Yamauchi Atsushi, Takeuchi Toshiharu, Kawabe Jun-ichi, Hasebe Naoyuki
Department of Internal Medicine, Division of Cardiology, Nephrology, Pulmonology and Neurology, Asahikawa Medical University (AMU), Asahikawa, Japan.
Department of Cardiovascular Regeneration and Innovation, Asahikawa Medical University (AMU), Asahikawa, Japan.
PLoS One. 2015 Apr 13;10(4):e0123733. doi: 10.1371/journal.pone.0123733. eCollection 2015.
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.
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.
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.
Microalbuminuria in AMI patients is closely associated with functional disorder of EPCs via cellular senescence, that predicts the aggravation of coronary remodeling after PCI.
探讨微量白蛋白尿与冠心病患者不良预后之间的关系，但其潜在的病理生理机制仍不清楚。我们研究了微量白蛋白尿对内皮祖细胞（EPCs）功能的作用，这可能会影响急性心肌梗死（AMI）患者的预后。
45例AMI患者根据尿白蛋白排泄量分为两组：正常组（n = 24）和微量白蛋白尿组（>30 mg/天，n = 21）。在AMI发病后第2天和第7天，通过流式细胞术对循环EPCs（CD34+ Flk1+）进行定量。测定固定在纤连蛋白上的凝集素-acLDL阳性培养EPCs的数量。为评估培养EPCs的细胞衰老情况，评估sirtuin-1 mRNA的表达水平和SA-β-半乳糖苷酶阳性细胞的数量。在六个月的随访中评估经皮冠状动脉介入治疗（PCI）后血管造影的晚期支架内血栓形成。
两组之间在冠心病风险和心肌损伤程度方面未观察到显著差异。微量白蛋白尿组在六个月随访时的晚期支架内血栓形成明显更高（正常组：微量白蛋白尿组 = 0.76±0.34:1.18±0.57 mm，p = 0.021）。微量白蛋白尿组在第7天时循环EPCs数量显著增加，然而，从基线到第7天，正常组观察到EPCs的黏附改善，而微量白蛋白尿组未观察到（+3.1±8.3:-1.3±4.4%: p<0.05）。另一方面，在第7天的微量白蛋白尿组中，培养EPCs的sirtuin-1 mRNA表达水平显著降低（7.1±8.9:2.5±3.7倍，p<0.05），这基于sirtuin-1 mRNA表达水平与微量白蛋白尿程度之间的负相关。微量白蛋白尿组中SA-β-半乳糖苷酶阳性细胞的比例高于正常组。
AMI患者的微量白蛋白尿通过细胞衰老与EPCs的功能障碍密切相关，这预示着PCI后冠状动脉重塑的加重。
