TGFβ/activin signaling pathway activation in intimal hyperplasia and atherosclerosis

Rahmi Öklü, Robin Hesketh, Stephan Wicky, James Metcalfe

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

PURPOSE: Intimal hyperplasia and atherosclerosis are the Achilles' heels of vascular interventions. Many cytokines and growth factors have been shown to mediate these pathological processes. There are conflicting data concerning the expression of transforming growth factor-β1 (TGF β11) antigen in human intimal hyperplasia and atherosclerotic lesions and conflicting views about whether TGF β1 is pro-or anti-atherogenic. The presence of TGFβ1 is not sufficient to infer activation of its signaling pathway because TGF β1 may be present in inactive complexes. MATERIALS AND METHODS A sensitive immuno-fluorescence assay (cyanine-3 tyramide signal amplification system) was used on human coronary artery and aorta sections with early or advanced stage lesions to detect TGFβ1, activin, Smad2-P, a marker of the activated TGF β1/activin pathway and components of latent TGFβ complexes. RESULTS All antigens were readily detected in the media and neointima of early stage lesions. The levels were either reduced or undetectable in the media of advanced lesions but were increased in the neointima in areas of high cell density. In marked contrast to activin, TGFβ1 and LAP1 expression levels were closely correlated with Smad2-P throughout the artery wall. CONCLUSION Discrepancies in previous data for TGFβ1 expression are probably due to assay sensitivity. TGFβ1, but not activin, expression is consistently correlated with Smad pathway activation in the artery wall. The pattern of Smad2 activation supports a model in which TGFβ/activin signaling is anti-atherogenic in the media of normal artery walls but is equally compatible with an anti-atherogenic or pro-atherogenic response to TGFβ/activin in the neointima of lesions.

Original languageEnglish (US)
Pages (from-to)290-296
Number of pages7
JournalDiagnostic and Interventional Radiology
Volume17
Issue number3
DOIs
StatePublished - Sep 1 2011

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Keywords

  • Atherosclerosis
  • Coronary artery disease
  • Immunohistochemistry
  • Vascular intima

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

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