Increase in circulating endothelial precursors by atorvastatin in patients with systemic sclerosis.
OBJECTIVE
To evaluate whether atorvastatin can increase bone marrow-derived circulating endothelial precursors (CEPs) and improve the vascular symptoms in patients with systemic sclerosis (SSc; scleroderma).


METHODS
The study was designed as an open-label, prospective study involving 14 patients with SSc who received 10 mg/day of atorvastatin for 12 weeks and were followed up for the subsequent 4 weeks. CEPs were quantified at weeks 0 (pretreatment), 4, 8, 12 (during treatment), and 16 (posttreatment) by cell sorting followed by 3-color flow cytometry. Raynaud's phenomenon variables, global measures, and psychological scales as well as circulating angiogenic factors and endothelial activation/injury markers were serially assessed. The potential of CEPs to differentiate into mature endothelial cells was examined in cultures with angiogenic stimuli.


RESULTS
None of the patients experienced an adverse event, but 1 dropped out because of an excessive decrease in serum total cholesterol. Atorvastatin treatment resulted in a 1.7- to 8.0-fold increase in CEPs from baseline levels (P < 0.0001), but the numbers returned to within baseline levels at posttreatment. However, 8 patients (62%) experienced a gradual decrease in the number of CEPs, even while taking atorvastatin. Variables indicating the extent of Raynaud's phenomenon improved significantly, and up-regulated levels of angiogenic factors and vascular endothelial activation/injury markers decreased significantly during atorvastatin treatment. These variables returned to within baseline levels after discontinuation of the drug. In contrast, atorvastatin failed to improve the in vitro maturation potential of CEPs.


CONCLUSIONS
The results of this pilot study suggest that atorvastatin treatment can increase CEPs and may be effective in improving Raynaud's phenomenon, even in SSc patients who have CEP dysfunction intrinsically.
Kuwana
Masataka
M
Keio University School of Medicine, Tokyo, Japan. kuwanam@sc.itc.keio.ac.jp
Kaburaki
Junichi
J
Okazaki
Yuka
Y
Yasuoka
Hidekata
H
Kawakami
Yutaka
Y
Ikeda
Yasuo
Y
D000328:Adult; D000368:Aged; D000069059:Atorvastatin; D004730:Endothelium, Vascular / Q000166:cytology*; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008875:Middle Aged; D011446:Prospective Studies; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D012595:Scleroderma, Systemic / Q000188:drug therapy*
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin