The relationship between endothelial progenitor cell populations and epicardial and microvascular coronary disease-a cellular, angiographic and physiologic study

Kim H Chan; Philippa J L Simpson; Andy S Yong; Louise L Dunn; Chirapan Chawantanpipat; Chijen Hsu; Young Yu; Anthony C Keech; David S Celermajer; Martin K C Ng

doi:10.1371/journal.pone.0093980

The relationship between endothelial progenitor cell populations and epicardial and microvascular coronary disease-a cellular, angiographic and physiologic study

PLoS One. 2014 Apr 15;9(4):e93980. doi: 10.1371/journal.pone.0093980. eCollection 2014.

Authors

Affiliations

¹ Department of Cardiology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia; The Heart Research Institute, Sydney, New South Wales, Australia; Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
² The Heart Research Institute, Sydney, New South Wales, Australia.
³ Department of Cardiology, Concord Hospital, Sydney, New South Wales, Australia.
⁴ Department of Cardiology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
⁵ Department of Cardiology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia; Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia; National Health and Medical Research Council Clinical Trials Centre, Sydney, New South Wales, Australia.

Abstract

Background: Endothelial progenitor cells (EPCs) are implicated in protection against vascular disease. However, studies using angiography alone have reported conflicting results when relating EPCs to epicardial coronary artery disease (CAD) severity. Moreover, the relationship between different EPC types and the coronary microcirculation is unknown. We therefore investigated the relationship between EPC populations and coronary epicardial and microvascular disease.

Methods: Thirty-three patients with a spectrum of isolated left anterior descending artery disease were studied. The coronary epicardial and microcirculation were physiologically interrogated by measurement of fractional flow reserve (FFR), index of microvascular resistance (IMR) and coronary flow reserve (CFR). Two distinct EPC populations (early EPC and late outgrowth endothelial cells [OECs]) were isolated from these patients and studied ex vivo.

Results: There was a significant inverse relationship between circulating OEC levels and epicardial CAD severity, as assessed by FFR and angiography (r=0.371, p=0.04; r=-0.358, p=0.04; respectively). More severe epicardial CAD was associated with impaired OEC migration and tubulogenesis (r=0.59, p=0.005; r=0.589, p=0.004; respectively). Patients with significant epicardial CAD (FFR<0.75) had lower OEC levels and function compared to those without hemodynamically significant stenoses (p<0.05). In contrast, no such relationship was seen for early EPC number and function, nor was there a relationship between IMR and EPCs. There was a significant relationship between CFR and OEC function.

Conclusions: EPC populations differ in regards to their associations with CAD severity. The number and function of OECs, but not early EPCs, correlated significantly with epicardial CAD severity. There was no relationship between EPCs and severity of coronary microvascular disease.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Cell Count
Coronary Angiography
Coronary Artery Disease / diagnosis
Coronary Artery Disease / metabolism
Coronary Artery Disease / physiopathology
Coronary Circulation*
Coronary Disease / diagnosis
Coronary Disease / metabolism*
Coronary Disease / physiopathology*
Endothelial Cells / metabolism
Endothelial Progenitor Cells / drug effects
Endothelial Progenitor Cells / metabolism*
Female
Hemodynamics
Humans
Male
Microcirculation*
Middle Aged
Pericardium / metabolism*
Prospective Studies
Severity of Illness Index

Grants and funding

Dr. Chan was supported by the National Heart Foundation scholarship (PC 08S 4127) and Royal Australasian College of Physicians scholarship. This study was supported by a grant from the National Health and Medical Research Council to Dr. Ng (No. 1013027). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.