Endothelial Alpha-Parvin Controls Integrity of Developing Vasculature and Is Required for Maintenance of Cell-Cell Junctions
العنوان: | Endothelial Alpha-Parvin Controls Integrity of Developing Vasculature and Is Required for Maintenance of Cell-Cell Junctions |
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المؤلفون: | Stefan Zahler, Holger Gerhardt, Julian Kirsch, Ulrich Pohl, Abdallah Abu Taha, Alessia Fraccaroli, Eloi Montanez, Jochen Seebach, Hans-J. Schnittler, Stephan Huveneers, Ricardo P. Casaroli-Marano, Bettina Pitter |
المساهمون: | Landsteiner Laboratory |
المصدر: | Circulation research, 117(1), 29-40. Lippincott Williams and Wilkins Circulation Research |
سنة النشر: | 2015 |
مصطلحات موضوعية: | Male, Physiology, Angiogenesis, growth and development, Neovascularization, Physiologic, Mice, Transgenic, Biology, Cell junction, blood vessels, cell adhesion molecules, Adherens junction, Focal adhesion, Extracellular matrix, angiogenesis, Mice, Antigens, CD, Cell Movement, In vivo, Human Umbilical Vein Endothelial Cells, Animals, Pseudopodia, RNA, Small Interfering, Cell Shape, Cells, Cultured, Cytoskeleton, Cadherin, Cell adhesion molecule, Microfilament Proteins, Endothelial Cells, Retinal Vessels, Adherens Junctions, Cadherins, Extracellular Matrix, Cell biology, Cellular Biology, Cardiovascular and Metabolic Diseases, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Female, Genes, Lethal, RNA Interference, Endothelium, Vascular, Cardiology and Cardiovascular Medicine |
الوصف: | Supplemental Digital Content is available in the text. Rationale: Angiogenesis and vessel integrity depend on the adhesion of endothelial cells (ECs) to the extracellular matrix and to adjacent ECs. The focal adhesion protein α-parvin (α-pv) is essential for vascular development. However, the role of α-pv in ECs in vivo is not known. Objective: To determine the function of α-pv in ECs during vascular development in vivo and the underlying mechanisms. Methods and Results: We deleted the α-pv gene specifically in ECs of mice to study its role in angiogenesis and vascular development. Here, we show that endothelial-specific deletion of α-pv in mice results in late embryonic lethality associated with hemorrhages and reduced vascular density. Postnatal-induced EC-specific deletion of α-pv leads to retinal hypovascularization because of reduced vessel sprouting and excessive vessel regression. In the absence of α-pv, blood vessels display impaired VE-cadherin junction morphology. In vitro, α-pv–deficient ECs show reduced stable adherens junctions, decreased monolayer formation, and impaired motility, associated with reduced formation of integrin-mediated cell–extracellular matrix adhesion structures and an altered actin cytoskeleton. Conclusions: Endothelial α-pv is essential for vessel sprouting and for vessel stability. |
وصف الملف: | application/pdf |
اللغة: | English |
تدمد: | 0009-7330 |
DOI: | 10.1161/circresaha.117.305818 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::21e6700ddcc5a27a140df17e6bf6be8c https://doi.org/10.1161/circresaha.117.305818 |
Rights: | OPEN |
رقم الانضمام: | edsair.doi.dedup.....21e6700ddcc5a27a140df17e6bf6be8c |
قاعدة البيانات: | OpenAIRE |
تدمد: | 00097330 |
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DOI: | 10.1161/circresaha.117.305818 |