ArticleJournal of the American Heart Association2018
Inhibiting Integrin α5 Cytoplasmic Domain Signaling Reduces Atherosclerosis and Promotes Arteriogenesis.
Article in Journal of the American Heart Association, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Endothelial GPR68 Is Essential for Arteriogenesis and Represents a Therapeutic Target in a Model of Peripheral Artery Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Fibronectin-dependent integrin signaling drives EphA2 expression in vascular smooth muscle cells.American journal of physiology. Cell physiology · 2025Article
- Phosphorylation of endothelial histone H3.3 serine 31 by PKN1 links flow-induced signaling to proatherogenic gene expression.Nature cardiovascular research · 2025Article
- Integrated Single-Cell Analysis Revealed Novel Subpopulations of Foamy Macrophages in Human Atherosclerotic Plaques.Biomolecules · 2024Article
- Mechanosensory entities and functionality of endothelial cells.Frontiers in cell and developmental biology · 2024Review
- Integrin αProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Extracellular Matrix Remodeling in Vascular Disease: Defining Its Regulators and Pathological Influence.Arteriosclerosis, thrombosis, and vascular biology · 2023Review
- FN (Fibronectin)-Integrin α5 Signaling Promotes Thoracic Aortic Aneurysm in a Mouse Model of Marfan Syndrome.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- Cathepsin K contributed to disturbed flow-induced atherosclerosis is dependent on integrin-actin cytoskeleton-NF-κB pathway.Genes & diseases · 2023Article
- Scavenger receptor-targeted plaque delivery of microRNA-coated nanoparticles for alleviating atherosclerosis.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Article
- The role of caveolae in endothelial dysfunction.Medical review (2021) · 2021Article
- Fibronectin-Mediated Inflammatory Signaling Through Integrin α5 in Vascular Remodeling.Journal of the American Heart Association · 2021Article
- Different Approaches in Therapy Aiming to Stabilize an Unstable Atherosclerotic Plaque.International journal of molecular sciences · 2021Review
- Sex-Stratified Gene Regulatory Networks Reveal Female Key Driver Genes of Atherosclerosis Involved in Smooth Muscle Cell Phenotype Switching.Circulation · 2021Article
- Integrin affinity modulation critically regulates atherogenic endothelial activation in vitro and in vivo.Matrix biology : journal of the International Society for Matrix Biology · 2021Article
- Disturbed flow-induced Gs-mediated signaling protects against endothelial inflammation and atherosclerosis.JCI insight · 2020Article
- Integrin α5β1 regulates PP2A complex assembly through PDE4D in atherosclerosis.The Journal of clinical investigation · 2019Article
- β1 integrin is a sensor of blood flow direction.Journal of cell science · 2019Article
- Nanoparticles That Deliver RNA to Bone Marrow Identified by in Vivo Directed Evolution.Journal of the American Chemical Society · 2018Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundFibronectin in endothelial basement membranes promotes endothelial inflammatory activation and atherosclerosis but also promotes plaque stability and vascular remodeling. The fibronectin receptor α5 subunit is proinflammatory through binding to and activating phosphodiesterase 4D5, which inhibits anti-inflammatory cyclic adenosine monophosphate and protein kinase A. Replacing the α5 cytoplasmic domain with that of α2 resulted in smaller atherosclerotic plaques. Here, we further assessed plaque phenotype and compensatory vascular remodeling in this model. METHODS AND
resultsα5/2 mice in the hyperlipidemic apolipoprotein E null background had smaller plaques in the aortic root, with reduced endothelial NF-κB activation and inflammatory gene expression, reduced leukocyte content, and much lower metalloproteinase expression. However, smooth muscle cell content, fibrous cap thickness, and fibrillar collagen were unchanged, indicating no shift toward vulnerability. In vivo knockdown of phosphodiesterase 4D5 also decreased endothelial inflammatory activation and atherosclerotic plaque size. α5/2 mice showed improved recovery from hindlimb ischemia after femoral artery ligation.
conclusionsBlocking the fibronectin-Integrin α5 pathway reduces atherosclerotic plaque size, maintains plaque stability, and improves compensatory remodeling. This pathway is therefore a potential therapeutic target for treatment of atherosclerosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.