Zeitschrift fur Kardiologie · 2001
Vascular repair processes mediated by transforming growth factor-beta.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Lindner V
Аннотация
OBJECTIVES: The goal of this study was to determine the role of transforming growth factor-beta (TGF-beta) family members in arterial repair processes related to vascular injury.
BACKGROUND: TGF-beta plays important roles in many tissues including calcifying tissues and blood vessels. The family members of TGF-beta 1, -beta 2, and -beta 3 have overlapping functions and signal via the same receptor complex. To examine the role of TGF-beta in vascular remodeling and intimal hyperplasia we disrupted this signaling pathway using recombinant soluble TGF-beta receptor II (TGF-beta R:Fc).
METHODS: The balloon catheter injury model of the rat carotid artery was used and TGF-beta R:Fc was injected every other day for a period of two weeks after which the vessels were harvested for analysis by histology, morphometry, and Northern blotting.
RESULTS: In situ hybridization showed TGF-beta receptor II expression in smooth muscle cells (SMC) of the injured vessel wall while the same cells also revealed abundant expression of all three TGF-beta ligands. Injection of TGF-beta R:Fc localized to the adventitia and developing neointima in the injured carotid artery, causing a reduction in intimal lesion formation (65%) and an increase in lumen area (88%). The increase in lumen area was largely due to inhibition of negative remodeling which coincided with reduced adventitial fibrosis and collagen synthesis. Four days after injury, TGF-beta R:Fc treatment almost completely inhibited the induction of smooth muscle alpha-actin expression in adventitial cells.
CONCLUSIONS: These results identify TGF-beta isoforms as the major mediators of adventitial fibrosis and negative remodeling after arterial injury, which is a major cause for restenosis following angioplasty.
BACKGROUND: TGF-beta plays important roles in many tissues including calcifying tissues and blood vessels. The family members of TGF-beta 1, -beta 2, and -beta 3 have overlapping functions and signal via the same receptor complex. To examine the role of TGF-beta in vascular remodeling and intimal hyperplasia we disrupted this signaling pathway using recombinant soluble TGF-beta receptor II (TGF-beta R:Fc).
METHODS: The balloon catheter injury model of the rat carotid artery was used and TGF-beta R:Fc was injected every other day for a period of two weeks after which the vessels were harvested for analysis by histology, morphometry, and Northern blotting.
RESULTS: In situ hybridization showed TGF-beta receptor II expression in smooth muscle cells (SMC) of the injured vessel wall while the same cells also revealed abundant expression of all three TGF-beta ligands. Injection of TGF-beta R:Fc localized to the adventitia and developing neointima in the injured carotid artery, causing a reduction in intimal lesion formation (65%) and an increase in lumen area (88%). The increase in lumen area was largely due to inhibition of negative remodeling which coincided with reduced adventitial fibrosis and collagen synthesis. Four days after injury, TGF-beta R:Fc treatment almost completely inhibited the induction of smooth muscle alpha-actin expression in adventitial cells.
CONCLUSIONS: These results identify TGF-beta isoforms as the major mediators of adventitial fibrosis and negative remodeling after arterial injury, which is a major cause for restenosis following angioplasty.