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Transforming growth factor-beta mediates balance between inflammation and fibrosis during plaque progression

Lutgens, E., Gijbels, M., Smook, M., Heeringa, P., Gotwals, P., Koteliansky, VE. & Daemen, MJAP., Jun-2002, In : Arteriosclerosis thrombosis and vascular biology. 22, 6, p. 975-982 8 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • E Lutgens
  • M Gijbels
  • M Smook
  • P Heeringa
  • P Gotwals
  • VE Koteliansky
  • MJAP Daemen

The transition from stable to rupture-prone and ruptured atherosclerotic plaques involves many processes, including an altered balance between inflammation and fibrosis. An important mediator of both is transforming growth factor (TGF)-beta, and a pivotal role for TGF-beta in atherogenesis has been postulated. Here, we determine the in vivo effects of TGF-beta inhibition on plaque progression and phenotype in atherosclerosis. Recombinant soluble TGF-beta receptor II (TGFbetaRII:Fc), which inhibits TGF-beta signaling, was injected in apolipoprotein E-deficient mice for 12 weeks (50 mug, twice a week intraperitoneally) as early treatment (treatment age 5 to 17 weeks) and delayed treatment (age 17 to 29 weeks). In the early treatment group, inhibition of TGF-beta signaling treatment resulted in a prominent increase in CD3- and CD45-positive cells in atherosclerotic lesions. Most profound effects were found in the delayed treatment group. Plaque area decreased 37.5% after TGFbetaRII:Fc treatment. Moreover, plaque morphology changed into an inflammatory phenotype that was low in fibrosis: lipid cores were 64.6% larger, and inflammatory cell content had increased 2.7-fold. The amount of fibrosis decreased 49.6%, and intraplaque hemorrhages and iron and fibrin deposition were observed frequently. TGFbetaRII:Fc treatment did not result in systemic effects. These results reveal a pivotal role for TGF-beta in the maintenance of the balance between inflammation and fibrosis in atherosclerotic plaques.

Original languageEnglish
Pages (from-to)975-982
Number of pages8
JournalArteriosclerosis thrombosis and vascular biology
Volume22
Issue number6
Publication statusPublished - Jun-2002

    Keywords

  • atherosclerosis, transforming growth factor-beta, inflammation, fibrosis, TGF-BETA, ATHEROSCLEROTIC LESIONS, GENE-EXPRESSION, CAROTID ATHEROSCLEROSIS, RECEPTOR, MICE, DISEASE, FACTOR-BETA-1, INHIBITION, CELLS

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