Defective vasculogenesis in systemic sclerosis

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

Research output: Contribution to journalArticle

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Abstract

Background Typical vascular features of systemic sclerosis include low capillary density and vascular obliteration. The formation and repair of blood vessels in adults involve vasculogenesis, which is mediated through the recruitment of bone-marrow-derived circulating endothelial precursors (CEP). We investigated whether vasculogenesis is impaired in patients with systemic sclerosis. Methods Peripheral blood was obtained from 11 patients with systemic sclerosis, 11 with rheumatoid arthritis, and 11 healthy controls. Factors potentially affecting the CEP number were matched among the three groups. CEP (identified as circulating cells positive for CD34, CD133, and the type 2 receptor for vascular endothelial growth factor) were quantified by cell sorting and three-colour flow cytometry. The circulating concentrations of angiogenic factors were measured by ELISA. The potential of CEP to differentiate into endothelial cells was assessed by the upregulation of von Willebrand factor after in-vitro maturation treatment. Findings The absolute number of CEP was much lower in patients with systemic sclerosis than in patients with rheumatoid arthritis or healthy controls (median 274 [IQR 178-395] vs 1154 [653-1524] and 1074 [713-1186] per 20 mL peripheral blood, respectively; p<0·0001 by Kruskal-Wallis test. Paradoxically, circulating concentrations of most angiogenic factors were significantly higher in patients with systemic sclerosis than in healthy controls. The proportion of CEP that differentiated into endothelial cells was significantly lower in patients with systemic sclerosis than in healthy controls (p<0·0001, Mann-Whitney test). Interpretation Insufficient vascular repair machinery due to defective vasculogenesis might contribute to vasculopathy in systemic sclerosis. Relevance to practice As well as providing an important insight into the pathogenesis of this disorder, these findings suggest that dysregulated vasculogenesis might be important in other disorders with abnormalities in vascular formation, including those with excessive formation of new vessels such as cancer and those with deficient vessel formation such as atherosclerosis. Circulating endothelial precursors could be a novel target for therapeutic strategies for ischaemic complications in patients with systemic sclerosis.

Original languageEnglish
Pages (from-to)603-610
Number of pages8
JournalLancet
Volume364
Issue number9434
DOIs
Publication statusPublished - 2004 Aug 14

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Systemic Scleroderma
Blood Vessels
Angiogenesis Inducing Agents
Rheumatoid Arthritis
Endothelial Cells
Vascular Endothelial Growth Factor Receptor-2
von Willebrand Factor
Atherosclerosis
Flow Cytometry
Up-Regulation
Color
Bone Marrow
Enzyme-Linked Immunosorbent Assay
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kuwana, M., Okazaki, Y., Yasuoka, H., Kawakami, Y., & Ikeda, Y. (2004). Defective vasculogenesis in systemic sclerosis. Lancet, 364(9434), 603-610. https://doi.org/10.1016/S0140-6736(04)16853-0

Defective vasculogenesis in systemic sclerosis. / Kuwana, Masataka; Okazaki, Yuka; Yasuoka, Hidekata; Kawakami, Yutaka; Ikeda, Yasuo.

In: Lancet, Vol. 364, No. 9434, 14.08.2004, p. 603-610.

Research output: Contribution to journalArticle

Kuwana, M, Okazaki, Y, Yasuoka, H, Kawakami, Y & Ikeda, Y 2004, 'Defective vasculogenesis in systemic sclerosis', Lancet, vol. 364, no. 9434, pp. 603-610. https://doi.org/10.1016/S0140-6736(04)16853-0
Kuwana M, Okazaki Y, Yasuoka H, Kawakami Y, Ikeda Y. Defective vasculogenesis in systemic sclerosis. Lancet. 2004 Aug 14;364(9434):603-610. https://doi.org/10.1016/S0140-6736(04)16853-0
Kuwana, Masataka ; Okazaki, Yuka ; Yasuoka, Hidekata ; Kawakami, Yutaka ; Ikeda, Yasuo. / Defective vasculogenesis in systemic sclerosis. In: Lancet. 2004 ; Vol. 364, No. 9434. pp. 603-610.
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