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

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.

Triglyceride to HDL-cholesterol ratio as an independent risk factor for the poor development of coronary collateral circulation in elderly patients with ST-segment elevation myocardial infarction and acute total occlusion

“…[ 30 ] Nevertheless, a recently study found that the acute impact influence of high-dose lipid-lowering therapy on endothelial progenitor cells is of no avail in stable CAD patients. [ 31 ] It seems to be inconsistent with previous studies. The reason may be that the treatment time was too short to show the effect or the number of cases was too small, a total of only 38 cases.…”

Counting circulating endothelial cells in allo-HSCT: an ad hoc designed polychromatic flowcytometry-based panel versus the CellSearch System

“…results have been consequently confirmed in a typical endothelial damage disease (i.e. diabetes) 24 and in coronary artery disease patients (REMEDY clinical trial) 25 . Furthermore, by using the CellSearch system, we have just recently confirmed the role of CEC changes in the diagnostic definition of GVHD in the largest series of allo-HSCT patients 20 .…”

Enrichment of Circulating Endothelial Cells by CD34 Microbeads Followed by Enumeration Using Flow Cytometry

“…23 It is present on micro-and macro-endothelial vessels, for example, coronary artery endothelial cells, lung microvascular endothelial cells and liver endothelial cells. [24][25][26][27][28] In addition, the CD34 cell population in peripheral blood is small; CD34 beads are therefore more suitable to select the CECs from between redundant blood cells and the technical selection process using these microbeads is very practical. Moreover, previously, CD34 beads were used reliably for the isolation of HUVECs, endothelial colony-forming cells and for the detection of CECs in blood of patients after myocardial infarction, yet they have not previously been applied for CEC enumeration.…”