Data from: Anthrax toxin receptor 1 is essential for arteriogenesis in a mouse model of hindlimb ischemia

Anthrax toxin receptor 1/tumor endothelial marker 8 (Antxr1 or TEM8) is
up-regulated in tumor vasculature and serves as a receptor for anthrax
toxin, but its physiologic function is unclear. The objective of this
study was to evaluate the role of Antxr1 in arteriogenesis. The role of
Antxr1 in arteriogenesis was tested by measuring gene expression and
immunohistochemistry in a mouse model of hindlimb ischemia using wild-type
and ANTXR1-/- mice. Additional tests were performed by measuring gene
expression in in vitro models of fluid shear stress and hypoxia, as well
as in human muscle tissues obtained from patients having peripheral artery
disease. We observed that Antxr1 expression transiently increased in
ischemic tissues following femoral artery ligation and that its expression
was necessary for arteriogenesis. In the absence of Antxr1, the mean
arterial lumen area in ischemic tissues decreased. Antxr1 mRNA and protein
expression was positively regulated by fluid shear stress, but not by
hypoxia. Furthermore, Antxr1 expression was elevated in human peripheral
artery disease requiring lower extremity bypass surgery. These findings
demonstrate an essential physiologic role for Antxr1 in arteriogenesis and
peripheral artery disease, with important implications for managing
ischemia and other arteriogenesis-dependent vascular diseases.