LDL lipid apheresis rapidly increases peripheral endothelial progenitor cell competence.
OBJECTIVE
Endothelial progenitor cells (EPCs) have been shown to promote neovascularization under physiologic and pathologic conditions. Statins have been documented to increase the total number of circulating EPCs in long-term treated patients. Lipid apheresis is used to treat patient with refractory hyperlipidemia. The aim of our study was to evaluate whether lipid apheresis is associated with EPC mobilization.


METHODS
Thirteen patients with refractory hyperlipidemia (analysis at the beginning and at the end of a single lipid apheresis treatment) and 10 healthy controls were included into the study. For quantifying total peripheral EPCs, CD133+/Flk-1+ myelo-monocytic blood cells were enumerated by flow cytometry. The proliferative potential of EPCs was evaluated by a "colony-forming unit" assay. In some patients, EPC eNOS expression was evaluated before and after treatment.


RESULTS
Circulating EPCs and the cells' proliferative activity were lower in hyperlipidemia patients as compared to controls (0.14 +/- 0.07 vs. 0.6 +/- 0.14, P = 0.01, and 13.9 +/- 4.9 vs. 45.6 +/- 8.1, P = 0.0007). Lipid apheresis treatment was not associated with an increase in total EPCs. The cells' proliferative activity was strongly stimulated by lipid apheresis as reflected by an increase in the number of EPC colonies (13.9 +/- 4.9 to 34.1 +/- 7.3, P = 0.035). Analysis of EPC eNOS expression revealed a threefold increase in the cellular expression intensity after lipid apheresis.


CONCLUSIONS
Patients with refractory hyperlipidemia exhibit lower peripheral EPC numbers and a lower proliferative activity of circulating EPCs than healthy controls. A single lipid apheresis treatment significantly stimulates EPC proliferation, it furthermore increases cellular eNOS. In summary, these results show that lipid apheresis mediates beneficial effects on the EPC system as an essential element in the process of vascular repair in the human organism.
Patschan
Daniel
D
Zentrum Innere Medizin, Abteilung Nephrologie und Rheumatologie, Universitätsklinikum Göttingen, Göttingen 37075, Germany. d.patschan@gmail.com
Patschan
Susann
S
Henze
Elvira
E
Wessels
Johannes T
JT
Koziolek
Michael
M
Müller
Gerhard A
GA
D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D001781:Blood Component Removal; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D015971:Gene Expression Regulation, Enzymologic; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood* / Q000628:therapy*; D007958:Leukocyte Count; D008077:Lipoproteins, LDL; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis; D010455:Peptides / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; D008077:Lipoproteins, LDL; C000606023:PROM1 protein, human; D010455:Peptides; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D040301:Vascular Endothelial Growth Factor Receptor-2