Shear induced collateral artery growth modulated by endoglin but not by ALK1

Leonard Seghers, Margreet R. de Vries, Evangelia Pardali, Imo E. Hoefer, Beerend P. Hierck, Peter ten Dijke, Marie Jose Goumans, Paul H. A. Quax*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Transforming growth factor-beta (TGF-beta) stimulates both ischaemia induced angiogenesis and shear stress induced arteriogenesis by signalling through different receptors. How these receptors are involved in both these processes of blood flow recovery is not entirely clear. In this study the role of TGF-beta receptors 1 and endoglin is assessed in neovascularization in mice. Unilateral femoral artery ligation was performed in mice heterozygous for either endoglin or ALK1 and in littermate controls. Compared with littermate controls, blood flow recovery, monitored by laser Doppler perfusion imaging, was significantly hampered by maximal 40% in endoglin heterozygous mice and by maximal 49% in ALK1 heterozygous mice. Collateral artery size was significantly reduced in endoglin heterozygous mice compared with controls but not in ALK1 heterozygous mice. Capillary density in ischaemic calf muscles was unaffected, but capillaries from endoglin and ALK1 heterozygous mice were significantly larger when compared with controls. To provide mechanistic evidence for the differential role of endoglin and ALK1 in shear induced or ischaemia induced neovascularization, murine endothelial cells were exposed to shear stress in vitro. This induced increased levels of endoglin mRNA but not ALK1. In this study it is demonstrated that both endoglin and ALK1 facilitate blood flow recovery. Importantly, endoglin contributes to both shear induced collateral artery growth and to ischaemia induced angiogenesis, whereas ALK1 is only involved in ischaemia induced angiogenesis.
Original languageEnglish
Pages (from-to)2440-2450
Number of pages11
JournalJournal of Cellular and Molecular Medicine
Volume16
Issue number10
DOIs
Publication statusPublished - Oct 2012
Externally publishedYes

Keywords

  • TGF-beta
  • Angiogenesis
  • Arteriogenesis
  • Ischaemia
  • Shear stress

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