Reduced number and activity of circulating endothelial progenitor cells in patients with idiopathic pulmonary arterial hypertension.
BACKGROUND
Endothelial dysfunction plays a central and critical role in the initiation and development of idiopathic pulmonary arterial hypertension (IPAH), and a variety of evidence suggests that endothelial progenitor cells (EPCs) constitute one aspect of endothelium repair. In addition, transplantation of EPCs could attenuate pulmonary hypertension induced by monocrotaline in rats. However, it has not been examined and reported whether circulating EPCs from patients with IPAH are damaged.


METHODS
EPCs were isolated and cultured from patients with IPAH (n=20) and matched healthy volunteers (n=20). Circulating EPC numbers (enumerated as AC133+KDR+ cells) as well as migratory and adhesive activity were assessed. Blood levels of vascular endothelial growth factor (VEGF), homocysteine (Hcy), B-type natriuretic peptide (BNP), von Willebrand Factor (vWF) and interleukin-6 (IL-6) were also measured.


RESULTS
A significant decrease was observed in circulating EPC (AC133+KDR+ cells, 86.6+/-20.7cells/ml blood vs. 119.6+/-25.4cells/ml blood, P<0.001) numbers and the cell numbers expanded in vitro (47.2+/-14.5 vs. 70.7+/-15.2EPCs/x200 field; P<0.001) in patients with IPAH. EPCs from patients with IPAH were significantly impaired in their migratory capacity and ability to adhere to fibronectin. Blood levels of VEGF, Hcy, BNP, vWF and IL-6 were elevated in patients with IPAH. EPC numbers and activity were inversely related to Hcy, IL-6, BNP and vWF.


CONCLUSIONS
Our observations indicated that EPC numbers and functional capacity were impaired in patients with IPAH, which might not only give potential insight into the pathophysiological mechanisms but also might be useful for identifying suitable therapeutic targets in these patients.
Junhui
Zhu
Z
Department of Cardiology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou 310016, China.
Xingxiang
Wang
W
Guosheng
Fu
F
Yunpeng
Shang
S
Furong
Zhang
Z
Junzhu
Chen
C
D000328:Adult; D002448:Cell Adhesion / Q000502:physiology*; D042783:Endothelial Cells / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology*; D005080:Exercise Test / Q000379:methods; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D006976:Hypertension, Pulmonary / Q000378:metabolism*; D008297:Male; D013234:Stem Cells / Q000502:physiology*; D016138:Walking / Q000502:physiology