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

Abstract

ObjectiveRelationship 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.MethodsForty-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.ResultsNo 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.ConclusionsMicroalbuminuria in AMI patients is closely associated with functional disorder of EPCs via cellular senescence, that predicts the aggravation of coronary remodeling after PCI.

Associations of serum uric acid and urinary albumin with the severity of diabetic retinopathy in individuals with type 2 diabetes

“…Studies also have shown that microalbuminuria is an independent risk factor for cardiovascular diseases not only in hypertensive and diabetic individuals but also for general population [ 29 ]. In the people with acute myocardial infarction, microalbuminuria is closely associated with functional disorder of endothelial progenitor cells, predicting the aggravation of coronary remodeling after percutaneous coronary intervention [ 30 ]. There is a positive correlation between microalbuminuria and the severity of coronary artery disease in T2DM individuals [ 15 ].…”

Mikroalbuminüri, Kritik Uzuv İskemisi Sebebi ile Diz Altı Arterlere Uygulanan Endovasküler Tedavide Restenoz İçin Risk Faktörü Değildir.

“…In a study it is suggested that microalbuminuria of AMI patients is associated with EPC dysfunction, which aggravates coronary remodeling which may affect in-stent restosis 19 . Moreover endothelial cell and microvascular dysfunction related to MA may also contribute to augmented neointimal formation 20 . In or study we did not fi nd any statistically signifi cant association between restenosis of BTK angioplasty and amputation rate with microalbuminuria, which may Mean Rutherford Becker Class was signifi cantly decreased after a follow-up of 12 months, which refl ected the outcome of intervention, is good in both groups.…”

Therapeutic opportunities for senolysis in cardiovascular disease

“…When used to augment myocardial repair post‐infarction, the beneficial effects of EPC on cardiac function and the survival benefit are lost in cells treated with Gdf11 or TERT inhibitors [ 108 ]. Clinically, senescence in this population of cells correlates with risk of restenosis of coronary stents following percutaneous coronary intervention, suggesting an inability to positively remodel the vasculature [ 109 ].…”