title: Endothelial progenitor cells as a biological marker of peripheral artery disease.
abstract: The role of endothelial progenitor cells (EPCs) in peripheral artery disease (PAD) remains unclear. We hypothesized that EPC mobilization and function play a central role in the development of endothelial dysfunction and directly influence the degree of atherosclerotic burden in peripheral artery vessels. The number of circulating EPCs, defined as CD34(+)/KDR(+) cells, were assessed by flow cytometry in 91 subjects classified according to a predefined sample size of 31 non-diabetic PAD patients, 30 diabetic PAD patients, and 30 healthy volunteers. Both PAD groups had undergone endovascular treatment in the past. As a functional parameter, EPC colony-forming units were determined ex vivo. Apart from a broad laboratory analysis, a series of clinical measures using the ankle-brachial index (ABI), flow-mediated dilatation (FMD) and carotid intima-media thickness (cIMT) were investigated. A significant reduction of EPC counts and proliferation indices in both PAD groups compared to healthy subjects were observed. Low EPC number and pathological findings in the clinical assessment were strongly correlated to the group allocation. Multivariate statistical analysis revealed these findings to be independent predictors of disease appearance. Linear regression analysis showed the ABI to be a predictor of circulating EPC number (p=0.02). Moreover, the functionality of EPCs was correlated by linear regression (p=0.017) to cIMT. The influence of diabetes mellitus on EPCs in our study has to be considered marginal in already disease-affected patients. This study demonstrated that EPCs could predict the prevalence and severity of symptomatic PAD, with ABI as the determinant of the state of EPC populations in disease-affected groups.
authors.affiliation: Division of Clinical and Interventional Angiology, Swiss Cardiovascular Center, Inselspital, University Hospital Bern and University of Bern, Bern, Switzerland.
authors.forename: Lukas
authors.initials: L
authors.lastname: Bitterli
authors.affiliation: Division of Cardiovascular Medicine, Marienhospital Brühl, Brühl, Germany.
authors.forename: Samuel
authors.initials: S
authors.lastname: Afan
authors.affiliation: Division of Clinical and Interventional Angiology, Swiss Cardiovascular Center, Inselspital, University Hospital Bern and University of Bern, Bern, Switzerland.
authors.forename: Stephan
authors.initials: S
authors.lastname: Bühler
authors.affiliation: Division of Clinical and Interventional Angiology, Swiss Cardiovascular Center, Inselspital, University Hospital Bern and University of Bern, Bern, Switzerland.
authors.forename: Stefano
authors.initials: S
authors.lastname: DiSanto
authors.affiliation: Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland.
authors.forename: Marcel
authors.initials: M
authors.lastname: Zwahlen
authors.affiliation: Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland.
authors.forename: Kurt
authors.initials: K
authors.lastname: Schmidlin
authors.affiliation: Division of Clinical and Interventional Angiology, Swiss Cardiovascular Center, Inselspital, University Hospital Bern and University of Bern, Bern, Switzerland.
authors.forename: Zijang
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Division of Clinical and Interventional Angiology, Swiss Cardiovascular Center, Inselspital, University Hospital Bern and University of Bern, Bern, Switzerland.
authors.forename: Iris
authors.initials: I
authors.lastname: Baumgartner
authors.affiliation: Division of Clinical and Interventional Angiology, Swiss Cardiovascular Center, Inselspital, University Hospital Bern and University of Bern, Bern, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Diehm
authors.affiliation: Division of Cardiovascular Medicine, Marienhospital Brühl, Brühl, Germany kalka@marienhospital-bruehl.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kalka
mesh_terms: D000368:Aged; D055109:Ankle Brachial Index; D018952:Antigens, CD34 / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002452:Cell Count; D049109:Cell Proliferation; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D066026:Endothelial Progenitor Cells / Q000737:chemistry / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D058729:Peripheral Arterial Disease / Q000097:blood / Q000473:pathology* / Q000503:physiopathology; D011237:Predictive Value of Tests; D012720:Severity of Illness Index; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000097:blood
chemical_list: D018952:Antigens, CD34; D015415:Biomarkers; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: EPC; PAD; biomarker; endothelial function; endothelial progenitor cells; peripheral artery disease