title: Effect of rosuvastatin or its combination with omega-3 fatty acids on circulating CD34(+) progenitor cells and on endothelial colony formation in patients with mixed dyslipidaemia.
abstract: Hypercholesterolaemia is associated with a reduced number of circulating progenitor cells, a defect that is restored by statin therapy. We studied the effect of rosuvastatin monotherapy or its combination with omega-3 polyunsaturated fatty acids (ω-3 PUFAs) on progenitor cell number and function in patients with mixed dyslipidaemia.
  
  
  
  Fifty patients with mixed dyslipidaemia and fifty-five normolipidaemic, apparently healthy, age- and sex-matched volunteers participated in the study. Patients were randomized to receive a daily dose of either 40 mg rosuvastatin (R group, n = 26) or 10 mg rosuvastatin plus 2 g of ω-3 PUFAs (R + O group, n = 24). The number of circulating CD34(+) and CD34(+)/KDR(+) progenitor cells as well as the number of colony-forming units-endothelial cells (CFU-ECs) at 10 days of culture were assessed at baseline and 3 months post-treatment.
  
  
  
  The number of CD34(+) and CD34(+)/KDR(+) cells per 10,000 leukocytes as well as the number of CFU-ECs were significantly lower in both patient groups compared with healthy volunteers (all p = 0.03). A 3-month treatment with either R or R + O significantly increased circulating CD34(+) and CD34(+)/KDR(+) cells as well as the number of CFU-ECs compared with baseline (all p = 0.03). Importantly, the increase in the above parameters was inversely correlated with therapy-induced reduction in lipid parameters in both patient groups.
  
  
  
  Patients with mixed dyslipidaemia exhibit low numbers of circulating CD34(+) and CD34(+)/KDR(+) cells as well as CFU-ECs in culture, a defect restored by 3-month treatment with either high-rosuvastatin dose or a combination of low-rosuvastatin dose with ω-3 PUFAs. The pathophysiological meaning of our results regarding the increased cardiovascular risk in these patients remains to be established.
authors.affiliation: Atherothrombosis Research Centre/Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece.
authors.forename: Vasileios G
authors.initials: VG
authors.lastname: Chantzichristos
authors.affiliation: Department of Internal Medicine, School of Medicine, University of Ioannina, 45110 Ioannina, Greece.
authors.forename: Aris P
authors.initials: AP
authors.lastname: Agouridis
authors.affiliation: Department of Internal Medicine, School of Medicine, University of Ioannina, 45110 Ioannina, Greece.
authors.forename: Elisavet
authors.initials: E
authors.lastname: Moutzouri
authors.affiliation: Department of Cardiology and Institute of Cardiovascular Regeneration, Goethe University Frankfurt, Frankfurt am Main, 60590, Germany; German Centre of Cardiovascular Research (DZHK), Rhein-Main Partner Site, Frankfurt, Germany.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Stellos
authors.affiliation: Department of Internal Medicine, School of Medicine, University of Ioannina, 45110 Ioannina, Greece.
authors.forename: Moses S
authors.initials: MS
authors.lastname: Elisaf
authors.affiliation: Atherothrombosis Research Centre/Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece. Electronic address: atselep@uoi.gr.
authors.forename: Alexandros D
authors.initials: AD
authors.lastname: Tselepis
mesh_terms: D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000097:blood*; D002318:Cardiovascular Diseases / Q000188:drug therapy; D050171:Dyslipidemias / Q000188:drug therapy*; D004730:Endothelium, Vascular / Q000473:pathology*; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007962:Leukocytes / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D000068718:Rosuvastatin Calcium / Q000627:therapeutic use*; D013234:Stem Cells
chemical_list: D018952:Antigens, CD34; D015525:Fatty Acids, Omega-3; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D000068718:Rosuvastatin Calcium
keywords: CD34(+) cells; CD34(+)/KDR(+) cells; CFU-ECs; Mixed dyslipidaemia; Omega-3 polyunsaturated fatty acids; Rosuvastatin