The acute impact of high-dose lipid-lowering treatment on endothelial progenitor cells in patients with coronary artery disease-The REMEDY-EPC early substudy

PLoS One. 2017 Apr 10;12(4):e0172800. doi: 10.1371/journal.pone.0172800. eCollection 2017.

Abstract

Rationale and objective: Endothelial 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).

Methods: In 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.

Results: We 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)].

Conclusions: In 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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Anticholesteremic Agents / administration & dosage*
  • Anticholesteremic Agents / adverse effects
  • Atorvastatin / administration & dosage
  • Atorvastatin / adverse effects
  • Coronary Artery Disease / drug therapy*
  • Coronary Artery Disease / metabolism
  • Coronary Artery Disease / pathology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Therapy, Combination
  • Endothelial Progenitor Cells / drug effects*
  • Endothelial Progenitor Cells / metabolism
  • Endothelial Progenitor Cells / pathology
  • Ezetimibe / administration & dosage
  • Ezetimibe / adverse effects
  • Female
  • Flow Cytometry
  • Humans
  • Male
  • Middle Aged
  • Rosuvastatin Calcium / administration & dosage
  • Rosuvastatin Calcium / adverse effects

Substances

  • Anticholesteremic Agents
  • Rosuvastatin Calcium
  • Atorvastatin
  • Ezetimibe

Grants and funding

This study was supported by grants from the Italian Istituto Nazionale Ricerche Cardiovascolari (I.N.R.C.), the Italian Ministry of the University and Research (PRIN projects), and the CARIPLO Foundation (to R.D.C.). The REMEDY Study, including the provision of drug treatments here compared, was initially supported by a grant from AstraZeneca Italy. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.