Requirement of β1 integrin for endothelium-dependent vasodilation and collateral formation in hindlimb ischemia
| Autor: | Eckhard Lammert, Malte Kelm, Daniel Eberhard, Jelle Ludolf Postma, Patrik Huelsemann, Christian Heiss, Dominik Schuler, Ferdinand le Noble, Christopher Nicolaus, Carina Henning, Dimitrios Dimitroulis, Anna Branopolski, Roberto Sansone |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Angiogenesis lcsh:Medicine Vasodilation Hindlimb Femoral artery 030204 cardiovascular system & hematology Neovascularization Gene Knockout Techniques Mice 0302 clinical medicine Enos Ischemia lcsh:Science Mice Knockout Multidisciplinary biology Integrin beta1 Blood flow medicine.anatomical_structure medicine.symptom Protein Binding Life sciences medicine.medical_specialty Endothelium Nitric Oxide Synthase Type III Collateral Circulation Neovascularization Physiologic Article 03 medical and health sciences Internal medicine medicine.artery ddc:570 medicine Animals Humans business.industry lcsh:R Endothelial Cells biology.organism_classification Disease Models Animal 030104 developmental biology Endocrinology lcsh:Q Arteriogenesis Endothelium Vascular business |
| Zdroj: | Scientific reports, 9 (1), Article no: 16931 Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-10 (2019) |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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