ArticleLaboratory investigation; a journal of technical methods and pathology2014
γ-Secretase inhibitor DAPT attenuates intimal hyperplasia of vein grafts by inhibition of Notch1 signaling.
Article in Laboratory investigation; a journal of technical methods and pathology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 20 citations in OpenAlex.
- Review
- [Advances in pharmacological research for retinopathy of prematurity].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2025Review
- Salidroside promotes pro-angiogenesis and repair of blood brain barrier via Notch/ITGB1 signal path in CSVD Model.Journal of advanced research · 2025Article
- Gamma-Secretase Inhibitor, DAPT, Prevents the Development of Retinopathy of Prematurity in a Rat Model by Regulating the Delta-Like Ligand 4/Notch Homolog-1 (DLL4/Notch-1) Pathway.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
- Effects of NOTCH1 signaling inhibitor γ-secretase inhibitor II on growth of cancer stem cells.Oncology letters · 2018Article
- Arterial Venous Differentiation for Vascular Bioengineering.Annual review of biomedical engineering · 2018Review
- TNF-α promotes survival and migration of MSCs under oxidative stress via NF-κB pathway to attenuate intimal hyperplasia in vein grafts.Journal of cellular and molecular medicine · 2017Article
- Article
- Delta-Like Ligand 4-Notch Signaling in Macrophage Activation.Arteriosclerosis, thrombosis, and vascular biology · 2016Review
- Role of Notch-1 signaling pathway in PC12 cell apoptosis induced by amyloid beta-peptide (25-35).Neural regeneration research · 2014Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The proliferation and high plasticity of vascular smooth muscle cells (vSMCs) are the major reasons for restenosis of vein grafts. N-[N-(3, 5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT), specific inhibitor of γ-secretase, has been shown to regulate vSMC proliferation and differentiation through the Notch signaling pathway, but the pathophysiological importance of these findings in venous grafts has not yet been determined. A rat vein graft model was employed wherein the left jugular vein was surgically interposed into the left common carotid artery. Daily subcutaneous injections of DAPT or placebo (DMSO) were administered postoperatively (control animals received no treatment). We showed that DAPT can inhibit restenosis of vein grafts by inhibiting vSMC proliferation and increasing apoptosis in vivo. Notch1 signaling was highly active during the development of intima thickening. By blocking the Notch signaling pathway, the γ-secretase inhibitor DAPT can significantly attenuated intima thickening. These changes in vein grafts coincided with enhanced binding of myocardin to the smooth muscle-specific protein SM22 and smooth muscle myosin heavy chain at the promoters of vSMC differentiation-specific genes. These studies showed that DAPT can restore the vSMC phenotype and inhibit vSMC proliferation through suppression of the Notch1 signaling pathway, and thus opens a new avenue for the treatment of restenosis in vein grafts.
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