Altered apoptosis pattern during pharyngeal arch artery remodelling is associated with aortic arch malformations in Tgfβ2 knock-out mice

Daniël G.M. Molin, Marco C. DeRuiter, Lambertus J. Wisse, Mohamad Azhar, Thomas Doetschman, Robert E. Poelmann, Adriana C. Gittenberger-De Groot

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

Objective: The morphogenetic process underlying the remodelling of the embryonic mammalian pharyngeal arch artery system is unknown. Within this process, the right sixth, carotid ducts and the distal part of the dorsal aorta (right α-segment) regress. In order to unravel the underlying mechanism we studied the role of apoptosis in the normal regression of pharyngeal arch artery segments and in a mouse model that develops aortic arch malformations. Methods: Normal remodelling was studied in wild-type Swiss (CPBS) and altered remodelling in the Tgfβ2-/- compared to the Tgfβ2+/+ (Swiss/Bl6) strain using immunohistochemistry and morphometric analysis. Results: During normal remodelling, apoptosis occurs in the mesenchyme surrounding pharyngeal arch arteries before regression starts. With the onset of regression, apoptosis spreads from the mesenchyme to the media. Morphometric evaluation confirms the increase in apoptosis in the actin-positive media of the disappearing segments. In Tgfβ2-/-, aberrant apoptosis was found in both fourth arch arteries, whereas the right dorsal aorta lacks apoptosis associated with normal regression. Fourth arch hypoplasia is the main arch abnormality. In the most severe case, the fourth arch is interrupted and the right dorsal aorta α-segment persists, giving rise to aortic arch interruption type-B and an aberrant right subclavian artery. Conclusions: We have shown for the first time that specific vascular apoptosis patterns accompany normal regression and that the incidence of apoptosis is selectively altered in the case of arch artery abnormalities in Tgfβ2 knock-out mice.

Original languageEnglish (US)
Pages (from-to)312-322
Number of pages11
JournalCardiovascular Research
Volume56
Issue number2
DOIs
StatePublished - Nov 1 2002
Externally publishedYes

Keywords

  • Apoptosis
  • Arteries
  • Congenital defects
  • Developmental biology
  • Growth factors

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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