Different populations of circulating endothelial cells in patients with age-related macular degeneration: a novel insight into pathogenesis.
OBJECTIVE
Circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs) may serve as novel markers of endothelial dysfunction. The presence and clinical implications of CECs and the expression of endothelin (ET)-1, one of the most potent vasoconstrictors, have not been evaluated in patients with the neovascular form of age-related macular degeneration (AMD). This study was conducted to determine the different populations of endothelial cells (ECs) in the peripheral blood of AMD patients and to correlate these findings with the expression of ET-1 and the cytokines and growth factors responsible for EC migration and function.


METHODS
Peripheral blood samples were collected from 29 patients with diagnosed neovascular AMD and from 38 healthy control subjects. CD133(-)CD144(+) CECs and CD34(+)CD133(+)CD144(+) EPCs were counted and analyzed by flow cytometry. The intracellular expression of ET-1 in peripheral blood nuclear cells (PBNCs) was studied by using qRT-PCR, Western blot, and immunocytofluorescence assays, and ET-1, IGF-1, VEGF, SDF-1, and HGF plasma concentrations were measured in enzyme-linked immunosorbent assays.


RESULTS
Increased CECs and EPCs were found in the AMD patients compared with the counts in healthy individuals. The expression of intracellular ET-1 was significantly elevated in PBNCs from the AMD patients compared with the control subjects. In addition a significantly higher plasma concentration of IGF-1 was observed, but a lower SDF-1 level in the group of AMD patients.


CONCLUSIONS
These findings suggest that circulating endothelial cells, together with high ET-1 content, may contribute to the development of AMD. Further prospective investigations on the mechanism involved may be relevant to the potential treatment of this disease.
Machalinska
Anna
A
Department of Histology and Embryology, Pomeranian Medical University, Szczecin, Poland.
Safranow
Krzysztof
K
Dziedziejko
Violetta
V
Mozolewska-Piotrowska
Katarzyna
K
Paczkowska
Edyta
E
Klos
Patrycja
P
Pius
Ewa
E
Grymula
Katarzyna
K
Wiszniewska
Barbara
B
Karczewicz
Danuta
D
Machalinski
Boguslaw
B
D000368:Aged; D015703:Antigens, CD; D001775:Blood Circulation; D015153:Blotting, Western; D016207:Cytokines / Q000378:metabolism; D019332:Endothelin-1 / Q000097:blood; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008268:Macular Degeneration / Q000097:blood* / Q000209:etiology; D008297:Male; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D015703:Antigens, CD; D016207:Cytokines; D019332:Endothelin-1; D042461:Vascular Endothelial Growth Factor A; D007334:Insulin-Like Growth Factor I