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

Henning, Carina, Branopolski, Anna, Schuler, Dominik, Dimitroulis, Dimitrios, Huelsemann, Patrik, Nicolaus, Christopher, Sansone, Roberto, Postma, Jelle Ludolf, Eberhard, Daniel, Le Noble, Ferdinand , Kelm, Malte, Lammert, Eckhard and Heiss, Christian (2019) Requirement of β1 integrin for endothelium-dependent vasodilation and collateral formation in hindlimb ischemia Scientific Reports.

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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/6J 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.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
Henning, Carina
Branopolski, Anna
Schuler, Dominik
Dimitroulis, Dimitrios
Huelsemann, Patrik
Nicolaus, Christopher
Sansone, Roberto
Postma, Jelle Ludolf
Eberhard, Daniel
Le Noble, Ferdinand
Kelm, Malte
Lammert, Eckhard
Heiss, Christianc.heiss@surrey.ac.uk
Date : 25 October 2019
Copyright Disclaimer : Copyright 2019 The Authors.
Depositing User : Diane Maxfield
Date Deposited : 08 Nov 2019 10:49
Last Modified : 08 Nov 2019 10:49
URI: http://epubs.surrey.ac.uk/id/eprint/853085

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