Effects of atorvastatin on circulating CD34+/CD133+/ CD45- progenitor cells and indices of angiogenesis (vascular endothelial growth factor and the angiopoietins 1 and 2) in atherosclerotic vascular disease and diabetes mellitus.
BACKGROUND
Cardiovascular disease (CVD) remains a major cause of morbidity and mortality, especially in the presence of diabetes, possibly because of endothelial damage. Increased circulating progenitor cells (CPCs) and increased plasma markers of angiogenesis [vascular endothelial growth factor (VEGF) and the angiopoietins (Ang-1 and -2)] may be evidence of this damage. Treatment with hydroxy-methyl-glutaryl (HMG-CoA) reductase inhibitors ('statins') improves outcomes in patients with vascular disease, including diabetic patients. We hypothesized that 80 mg per day atorvastatin influences CPC counts of VEGF and the angiopoietins in patients with atherosclerotic CVD with or without diabetes mellitus.


METHODS
Cardiovascular disease patients with diabetes mellitus (Group A, n = 14) and nondiabetic patients with CVD only (Group B, n = 10) took atorvastatin 80 mg per day for a period of 8-10 weeks. CPCs (CD34+/CD133+/CD45-) were defined by flow cytometry, plasma levels VEGF and Ang-1 and Ang-2 by ELISA).


RESULTS
Circulating progenitor cell counts increased (P < 0.001) in Group A compared with a nonsignificant change in Group B (P = 0.37). VEGF levels fell significantly in Group A (P = 0.04) but no significant change was seen in Group B (P = 0.16). Whilst Ang-1 remained unchanged (P = 0.41), Ang-2 levels increased markedly in both groups (P < 0.05). These effects were independent of LDL and total cholesterol changes but were associated with HDL changes.


CONCLUSIONS
High-dose atorvastatin increased circulating CPCs, reduced VEGF and increased Ang-2 in patients with diabetes and CVD, providing another possible pathophysiological mechanism for the beneficial effects of statins in CVD.
Jaumdally
R J
RJ
Centre for Cardiovascular Sciences, University of Birmingham, City Hospital, Birmingham, United Kingdom.
Goon
P K Y
PK
Varma
C
C
Blann
A D
AD
Lip
G Y H
GY
D000368:Aged; D042683:Angiopoietin-1 / Q000097:blood; D042702:Angiopoietin-2 / Q000097:blood; D015703:Antigens, CD / Q000097:blood*; D018952:Antigens, CD34 / Q000097:blood; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D000069059:Atorvastatin; D003920:Diabetes Mellitus / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D017493:Leukocyte Common Antigens / Q000097:blood; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000097:blood; D011446:Prospective Studies; D011758:Pyrroles / Q000627:therapeutic use*; D013234:Stem Cells; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D042683:Angiopoietin-1; D042702:Angiopoietin-2; D015703:Antigens, CD; D018952:Antigens, CD34; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D042461:Vascular Endothelial Growth Factor A; D000069059:Atorvastatin; D017493:Leukocyte Common Antigens