Increase in circulating endothelial precursors by atorvastatin in patients with systemic sclerosis

Masataka Kuwana, Junichi Kaburaki, Yuka Okazaki, Hidekata Yasuoka, Yutaka Kawakami, Yasuo Ikeda

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

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. Conclusion. 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.

Original languageEnglish
Pages (from-to)1946-1951
Number of pages6
JournalArthritis and Rheumatism
Volume54
Issue number6
DOIs
Publication statusPublished - 2006 Jun
Externally publishedYes

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Systemic Scleroderma
Raynaud Disease
Angiogenesis Inducing Agents
Blood Vessels
Wounds and Injuries
Therapeutics
Atorvastatin Calcium
Flow Cytometry
Endothelial Cells
Color
Bone Marrow
Cholesterol
Prospective Studies
Psychology
Serum
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

Cite this

Kuwana, M., Kaburaki, J., Okazaki, Y., Yasuoka, H., Kawakami, Y., & Ikeda, Y. (2006). Increase in circulating endothelial precursors by atorvastatin in patients with systemic sclerosis. Arthritis and Rheumatism, 54(6), 1946-1951. https://doi.org/10.1002/art.21899

Increase in circulating endothelial precursors by atorvastatin in patients with systemic sclerosis. / Kuwana, Masataka; Kaburaki, Junichi; Okazaki, Yuka; Yasuoka, Hidekata; Kawakami, Yutaka; Ikeda, Yasuo.

In: Arthritis and Rheumatism, Vol. 54, No. 6, 06.2006, p. 1946-1951.

Research output: Contribution to journalArticle

Kuwana, M, Kaburaki, J, Okazaki, Y, Yasuoka, H, Kawakami, Y & Ikeda, Y 2006, 'Increase in circulating endothelial precursors by atorvastatin in patients with systemic sclerosis', Arthritis and Rheumatism, vol. 54, no. 6, pp. 1946-1951. https://doi.org/10.1002/art.21899
Kuwana, Masataka ; Kaburaki, Junichi ; Okazaki, Yuka ; Yasuoka, Hidekata ; Kawakami, Yutaka ; Ikeda, Yasuo. / Increase in circulating endothelial precursors by atorvastatin in patients with systemic sclerosis. In: Arthritis and Rheumatism. 2006 ; Vol. 54, No. 6. pp. 1946-1951.
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abstract = "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. Conclusion. 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.",
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