Senescent endothelial progenitor cells from dogs with pulmonary arterial hypertension: a before-after self-controlled study.
Previous studies have underlined the importance of endothelial dysfunction and microvascular occlusion in the pathogenesis of pulmonary artery hypertension (PAH). Since the endothelial progenitor cells (EPCs) are involved in maintaining endothelial homeostasis, we observed the change of peripheral EPCs in canines before and after PAH onset. PAH was induced by intra-pulmonary artery injection of dehydromonocrotaline (DHMC) in nine beagles. Before and 48 h and 6 weeks after DHMC injection, 40 ml peripheral blood was obtained from the femoral vein. Circulating EPCs were identified as CD133 + KDR + cells and numerated by fluorescence-activated cell sorter; the EPCs functional capacity was determined by in vitro tubule-forming assay. The senescence of EPCs was determined by beta-galactosidase staining. At each time point, 2 ml blood from femoral artery was obtained for arterial oxygen pressure (PaO(2)). Forty-eight hours after DHMC injection, treated beagles suffered from hypoxemia; however, both the number and the tubule-forming capacity of EPCs were transiently raised. Six weeks later, PAH was confirmed by obviously high mean pulmonary arterial pressure (20.2 +/- 1.64 vs. 11.3 +/- 2.0 mmHg, p < 0.05) and low PaO(2) (69.30 +/- 9.15 vs. 95.94 +/- 1.43 mmHg, p < 0.01) in beagles after DHMC treatment, and their EPCs exhibited a predominant decrease in either the number (206.1 +/- 26.8 vs. 632.8 +/- 42.8 cells/ml blood, p < 0.01) or the tubule-forming capacity (21.1 +/- 2.8 vs. 11.2 +/- 2.8 tubules/x200 field, p < 0.01). Additionally, senescence-associated beta-galactosidase-positive EPCs were significantly increased. Our data suggested that, after the acute stage of DHMC injury to pulmonary vessels, the EPCs from PAH beagles suffered from exhaustion and senescence.
Xia
Liang
L
Department of Cardiology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, No. 3 Qingchun East Road, 310016, Hangzhou, Zhejiang, People's Republic of China.
Zhu
Jun-hui
JH
Qiu
Fu-yu
FY
Yang
Ying
Y
Xie
Xu-dong
XD
Wang
Xing-xiang
XX
Chen
Jun-zhu
JZ
Fu
Guo-sheng
GS
D000818:Animals; D018929:Cell Culture Techniques; D002469:Cell Separation; D002478:Cells, Cultured; D016922:Cellular Senescence; D004195:Disease Models, Animal; D004285:Dogs; D042783:Endothelial Cells / Q000378:metabolism / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology*; D005434:Flow Cytometry; D006976:Hypertension, Pulmonary / Q000139:chemically induced*; D008297:Male; D016686:Monocrotaline / Q000031:analogs & derivatives / Q000494:pharmacology; D018919:Neovascularization, Physiologic; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*
C014114:monocrotaline pyrrole; D016686:Monocrotaline