Immaturity of microvessels in haemorrhagic plaques is associated with proteolytic degradation of angiogenic factors

  • Le Dall J
  • Ho-Tin-Noé B
  • Louedec L
 et al. 
  • 28

    Readers

    Mendeley users who have this article in their library.
  • 22

    Citations

    Citations of this article.

Abstract

AIMS: We investigated the causes of microvessel immaturity and destabilization in human atherosclerotic lesions. METHODS AND RESULTS: Human atherosclerotic carotid plaques (n = 24) were classified as non-haemorrhagic (NH) or haemorrhagic (Hem), according to their macroscopic aspect and haemoglobin content. Plaque microvessel density and maturity were quantified by immunohistochemistry. Expression of angiogenic factors was studied by immunohistochemistry, in situ hybridization, and ELISA. Plaque-conditioned media were tested for plasmin and elastase activities and for their ability to degrade angiogenic factors and to induce smooth muscle cell migration. Microvessel density and leucocyte infiltration were increased in Hem compared with NH plaques. Plaque vasculature appeared vulnerable as indicated by the absence of alpha-actin-positive mural cells in most plaque vessels. Despite increased numbers of angiogenic factor-expressing microvessels and leucocytes in Hem plaques, lower levels of vascular endothelial growth factor, placental growth factor, and angiopoietin-1 were found in conditioned media from Hem plaques. However, NH and Hem plaques released similar levels of the vascular destabilizing factor, angiopoietin-2. Addition of recombinant angiogenic factors to plaque extracts showed that all factors but angiopoietin-2 were selectively degraded by plasmin and/or elastase released from Hem plaques. Furthermore, conditioned media from Hem plaques showed a reduced ability to induce smooth muscle cell migration. CONCLUSION: Our results provide evidence that immaturity of plaque vessels is associated with the degradation of angiogenic factors by haemorrhage-conveyed leucocytes and proteases.

Author-supplied keywords

  • Angiogenesis
  • Angiopoietins
  • Plasmin
  • VEGF

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free