ArticleCirculation research2013
Endothelial Shc regulates arteriogenesis through dual control of arterial specification and inflammation via the notch and nuclear factor-κ-light-chain-enhancer of activated B-cell pathways.
Article in Circulation research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 40 citations in OpenAlex.
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- Transient low shear-stress preconditioning influences long-term endothelial traction and alignment under high shear flow.American journal of physiology. Heart and circulatory physiology · 2024Article
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- Piezo1-Regulated Mechanotransduction Controls Flow-Activated Lymphatic Expansion.Circulation research · 2022Article
- The essential role for endothelial cell sprouting in coronary collateral growth.Journal of molecular and cellular cardiology · 2022Article
- Mechanical forces regulate endothelial-to-mesenchymal transition and atherosclerosis via an Alk5-Shc mechanotransduction pathway.Science advances · 2021Article
- Developmental Perspectives on Arterial Fate Specification.Frontiers in cell and developmental biology · 2021Review
- Review
- A key role for the novel coronary artery disease gene JCAD in atherosclerosis via shear stress mechanotransduction.Cardiovascular research · 2020Article
- The hydromechanics in arteriogenesis.Aging medicine (Milton (N.S.W)) · 2020Review
- NFAT5 promotes arteriogenesis via MCP-1-dependent monocyte recruitment.Journal of cellular and molecular medicine · 2020Article
- Translocating transcription factors in fluid shear stress-mediated vascular remodeling and disease.Experimental cell research · 2019Review
- Shear stress induces expression, intracellular reorganization and enhanced Notch activation potential of Jagged1.Integrative biology : quantitative biosciences from nano to macro · 2018Article
- MicroRNA-146a Regulates Perfusion Recovery in Response to Arterial OcclusionFrontiers in bioengineering and biotechnology · 2018Article
- Plasma Omentin-1 Level as a Predictor of Good Coronary Collateral Circulation.Journal of atherosclerosis and thrombosis · 2017Article
- Perpetual change: autophagy, the endothelium, and response to vascular injury.Journal of leukocyte biology · 2017Review
- Blood Brothers: Hemodynamics and Cell-Matrix Interactions in Endothelial Function.Antioxidants & redox signaling · 2016Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
rationaleArteriogenesis, the shear stress-driven remodeling of collateral arteries, is critical in restoring blood flow to ischemic tissue after a vascular occlusion. Our previous work has shown that the adaptor protein Shc mediates endothelial responses to shear stress in vitro.
objectiveTo examine the role of the adaptor protein Shc in arteriogenesis and endothelial-dependent responses to shear stress in vivo. METHODS AND
resultsConditional knockout mice in which Shc is deleted from endothelial cells were subjected to femoral artery ligation. Hindlimb perfusion recovery was attenuated in Shc conditional knockout mice compared with littermate controls. Reduced perfusion was associated with blunted collateral remodeling and reduced capillary density. Bone marrow transplantation experiments revealed that endothelial Shc is required for perfusion recovery because loss of Shc in bone marrow-derived hematopoietic cells had no effect on recovery. Mechanistically, Shc deficiency resulted in impaired activation of the nuclear factor κ-light-chain-enhancer of activated B-cell-dependent inflammatory pathway and reduced CD45⁺ cell infiltration. Unexpectedly, Shc was required for arterial specification of the remodeling arteriole by mediating upregulation of the arterial endothelial cell marker ephrinB2 and activation of the Notch pathway. In vitro experiments confirmed that Shc was required for shear stress-induced activation of the Notch pathway and downstream arterial specification through a mechanism that involves upregulation of Notch ligands delta-like 1 and delta-like 4.
conclusionsShc mediates activation of 2 key signaling pathways that are critical for inflammation and arterial specification; collectively, these pathways contribute to arteriogenesis and the recovery of blood perfusion.
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