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  • Requirement of β1 integrin for endothelium-dependent vasodilation and collateral formation in hindlimb ischemia.

Requirement of β1 integrin for endothelium-dependent vasodilation and collateral formation in hindlimb ischemia.

Scientific reports (2019-11-16)
Carina Henning, Anna Branopolski, Dominik Schuler, Dimitrios Dimitroulis, Patrik Huelsemann, Christopher Nicolaus, Roberto Sansone, Jelle Ludolf Postma, Daniel Eberhard, Ferdinand Le Noble, Malte Kelm, Eckhard Lammert, Christian Heiss
ABSTRACT

An acute increase in blood flow triggers flow-mediated dilation (FMD), which is mainly mediated by endothelial nitric oxide synthase (eNOS). A long-term increase in blood flow chronically enlarges the arterial lumen, a process called arteriogenesis. In several common human diseases, these processes are disrupted for as yet unknown reasons. Here, we asked whether β1 integrin, a mechanosensory protein in endothelial cells, is required for FMD and arteriogenesis in the ischemic hindlimb. Permanent ligation of the femoral artery in C57BL/6 J mice enlarged pre-existing collateral arteries and increased numbers of arterioles in the thigh. In the lower leg, the numbers of capillaries increased. Notably, injection of β1 integrin-blocking antibody or tamoxifen-induced endothelial cell-specific deletion of the gene for β1 integrin (Itgb1) inhibited both arteriogenesis and angiogenesis. Using high frequency ultrasound, we demonstrated that β1 integrin-blocking antibody or endothelial cell-specific depletion of β1 integrin attenuated FMD of the femoral artery, and blocking of β1 integrin function did not further decrease FMD in eNOS-deficient mice. Our data suggest that endothelial β1 integrin is required for both acute and chronic widening of the arterial lumen in response to hindlimb ischemia, potentially via functional interaction with eNOS.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Actin, α-Smooth Muscle - Cy3 antibody, Mouse monoclonal, clone 1A4, purified from hybridoma cell culture
Sigma-Aldrich
Anti-Integrin β1 Antibody, clone MB1.2, clone MB1.2, Chemicon®, from rat
Sigma-Aldrich
5-Bromo-4-chloro-3-indolyl β-D-galactopyranoside, ≥98%, powder
Roche
In Situ Cell Death Detection Kit, TMR red, sufficient for ≤50 tests