Description:
<jats:title>Abstract</jats:title><jats:p>Transforming growth factor‐beta (<jats:styled-content style="fixed-case">TGF‐β</jats:styled-content>) 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‐β receptors 1 and endoglin is assessed in neovascularization in mice. Unilateral femoral artery ligation was performed in mice heterozygous for either endoglin or <jats:styled-content style="fixed-case">ALK1</jats:styled-content> 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 <jats:styled-content style="fixed-case">ALK1</jats:styled-content> heterozygous mice. Collateral artery size was significantly reduced in endoglin heterozygous mice compared with controls but not in <jats:styled-content style="fixed-case">ALK1</jats:styled-content> heterozygous mice. Capillary density in ischaemic calf muscles was unaffected, but capillaries from endoglin and <jats:styled-content style="fixed-case">ALK1</jats:styled-content> heterozygous mice were significantly larger when compared with controls. To provide mechanistic evidence for the differential role of endoglin and <jats:styled-content style="fixed-case">ALK1</jats:styled-content> in shear induced or ischaemia induced neovascularization, murine endothelial cells were exposed to shear stress <jats:italic>in vitro</jats:italic>. This induced increased levels of endoglin <jats:styled-content style="fixed-case">mRNA</jats:styled-content> but not <jats:styled-content style="fixed-case">ALK1</jats:styled-content>. In this study it is demonstrated that both endoglin and <jats:styled-content style="fixed-case">ALK1</jats:styled-content> facilitate blood flow recovery. Importantly, endoglin contributes to both shear induced collateral artery growth and to ischaemia induced angiogenesis, whereas <jats:styled-content style="fixed-case">ALK1</jats:styled-content> is only involved in ischaemia induced angiogenesis.</jats:p>