Effects of rosuvastatin and allopurinol on circulating endothelial progenitor cells in patients with congestive heart failure: the impact of inflammatory process and oxidative stress.
OBJECTIVE
Endothelial progenitor cells (EPCs) contribute to the maintenance of endothelial integrity and function. We investigated the effects of rosuvastatin and allopurinol on the number of EPCs in patients with heart failure and aimed to provide insight into the molecular inflammatory and oxidative mechanisms that could be responsible for the alterations in EPC levels after treatment.


METHODS
Sixty patients with systolic heart failure were randomized to receive rosuvastatin 10mg/d, allopurinol 300mg/d or placebo and followed up for 1 month. The number of CD34(+)/KDR(+) and CD34(+)/CD133(+)/KDR(+) EPCs in blood was evaluated by flow cytometry. Endothelial function was assessed by brachial artery flow-mediated dilation. Levels of markers of inflammation and oxidative stress were also determined.


RESULTS
Circulating EPCs were significantly increased after rosuvastatin treatment (from 230 (170-380) and 10 (8-24) to 390 (230-520) and 19 (8-33) cells/10(6) lymphomonocytes, respectively, p=0.004 and p=0.008), whereas they remained unchanged in the other groups. The increase in EPC levels was not associated with the changes in the levels of the measured inflammatory and oxidative markers.


CONCLUSIONS
Short-term treatment with rosuvastatin, but not allopurinol, significantly increases the number of circulating EPCs in patients with heart failure providing further insights into its role in these individuals. The impact of rosuvastatin on EPCs is not mediated by changes in inflammatory and oxidative status.
1st Cardiology Department, Hippokration Hospital, Athens University Medical School, Athens, Greece. drtousoulis@hotmail.com
Dimitris
D
Tousoulis
Ioannis
I
Andreou
Marinos
M
Tsiatas
Antigoni
A
Miliou
Costas
C
Tentolouris
Gerasimos
G
Siasos
Nikos
N
Papageorgiou
Christos A
CA
Papadimitriou
Meletios-Athanasios
MA
Dimopoulos
Christodoulos
C
Stefanadis
D000071916:AC133 Antigen; D000368:Aged; D000493:Allopurinol / Q000627:therapeutic use*; D015703:Antigens, CD / Q000096:biosynthesis; D018952:Antigens, CD34 / Q000096:biosynthesis; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005464:Fluorobenzenes / Q000627:therapeutic use*; D006023:Glycoproteins / Q000096:biosynthesis; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D010455:Peptides; D009195:Peroxidase / Q000378:metabolism; D011743:Pyrimidines / Q000627:therapeutic use*; D000068718:Rosuvastatin Calcium; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D013449:Sulfonamides / Q000627:therapeutic use*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D004791:Enzyme Inhibitors; D005464:Fluorobenzenes; D006023:Glycoproteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C000606023:PROM1 protein, human; D010455:Peptides; D011743:Pyrimidines; D013449:Sulfonamides; D000493:Allopurinol; D000068718:Rosuvastatin Calcium; D009195:Peroxidase; D014969:Xanthine Oxidase; D040301:Vascular Endothelial Growth Factor Receptor-2