Abstract

Rationale and objectiveEndothelial progenitor cells (EPCs) play a role in vascular repair, while circulating endothelial cells (CECs) are biomarkers of vascular damage and regeneration. Statins may promote EPC/CEC mobilization in the peripheral blood. We evaluated whether pre-procedural exposure to different lipid-lowering drugs (statins±ezetimibe) can acutely increase levels/activity of EPCs/CECs in patients with stable coronary artery disease (CAD).MethodsIn a planned sub-analysis of the Rosuvastatin For REduction Of Myocardial DamagE During Coronary AngioplastY (REMEDY) trial, 38 patients with stable CAD on chronic low-dose statin therapy were randomized, in a double-blind, placebo-controlled design, into 4 groups before PCI: i. placebo (n = 11); ii. atorvastatin (80 mg+40 mg, n = 9); iii. rosuvastatin (40 mg twice, n = 9); and iv. rosuvastatin (5 mg) and ezetimibe (10 mg) twice, (n = 9). At baseline and 24 h after treatment–before PCI–, patients underwent blinded analyses of EPCs [colony forming units-endothelial cells (CFU-ECs), endothelial colony-forming cells (ECFCs) and tubulization activity] and CECs in peripheral blood.ResultsWe found no significant treatment effects on parameters investigated such as number of CECs [Median (IQR): i. 0(0), ii. 4.5(27), iii. 1.9(2.3), iv. 1.9(2.3)], CFU-ECs [Median (IQR): i. 27(11), ii. 19(31), iii. 47(36), iv. 30(98)], and ECFCs [Median (IQR): i. 86(84), ii. 7(84), iii. 8/(42.5), iv. 5(2)], as well as tubulization activity [total tubuli (well), Median (IQR): i. 19(7), ii. 5(4), iii. 25(13), iv. 15(24)].ConclusionsIn this study, we found no evidence of acute changes in levels or activity of EPCs and CECs after high-dose lipid-lowering therapy in stable CAD patients.

Highlights

  • Stem/progenitor cell transplantation or mobilization are emerging as promising new treatments for heart failure and myocardial infarction [1]

  • We found no evidence of acute changes in levels or activity of Endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) after high-dose lipid-lowering therapy in stable coronary artery disease (CAD) patients

  • Endothelial progenitor cells (EPCs) are rare progenitor cell subsets originated in the bone marrow, which are mobilized upon specific stimulation [2,3,4], homing to target tissues where they are involved in endothelial repair or remodeling, as well as in post-natal neo-vasculogenesis [5]

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Summary

Introduction

Stem/progenitor cell transplantation or mobilization are emerging as promising new treatments for heart failure and myocardial infarction [1]. EPCs appear to promote cardioprotection and cytoprotection by releasing paracrine factors, such as vascular endothelial growth factor (VEGF), granulocyte-colony stimulating factor (G-CSF), stem cell-derived factor (SDF)-1α and insulin growth factor (IGF)-1 [9, 10] Among their so called “pleiotropic effects”, independent of low-density lipoprotein (LDL) reduction, statins have been shown to efficiently increase levels of EPCs in patients with coronary artery disease (CAD) [11] and in patients with chronic heart failure [12], and to improve the proliferative capacity of EPCs, in a way similar to VEGF [11, 13, 14]. One hypothesis is that pre-procedural intensive statin treatment activates cardioprotection and vascular repair by stimulating proliferation, mobilization and homing of EPCs, with subsequent augmentation of circulating and cardiovascular tissue-resident EPCs, in a manner independent of cholesterol synthesis [23]

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