ArticleJournal of the American Heart Association2012
Histone deacetylase activity selectively regulates notch-mediated smooth muscle differentiation in human vascular cells.
Article in Journal of the American Heart Association, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 28 citations in OpenAlex.
- HDAC inhibition reprograms stem cell fate to suppress infantile hemangioma vasculogenesis.Angiogenesis · 2026Article
- Neointimal hyperplasia and vascular restenosis: from molecular mechanisms to therapeutic interventions.Molecular biomedicine · 2026Review
- Cell signaling and transcriptional regulation of osteoblast lineage commitment, differentiation, bone formation, and homeostasis.Cell discovery · 2024Review
- Hdac1 and Hdac2 positively regulate Notch1 gain-of-function pathogenic signaling in committed osteoblasts of male mice.Birth defects research · 2024Article
- Ubiquitin Proteasome Gene Signatures in Ependymoma Molecular Subtypes.International journal of molecular sciences · 2022Review
- HDAC4 Inhibitors as Antivascular Senescence Therapeutics.Oxidative medicine and cellular longevity · 2022Review
- Notch-ing up knowledge on molecular mechanisms of skin fibrosis: focus on the multifaceted Notch signalling pathway.Journal of biomedical science · 2021Review
- HDAC Inhibitor LBH589 Suppresses the Proliferation but Enhances the Antileukemic Effect of Human γδT Cells.Molecular therapy oncolytics · 2020Article
- Metformin inhibits intracranial aneurysm formation and progression by regulating vascular smooth muscle cell phenotype switching via the AMPK/ACC pathway.Journal of neuroinflammation · 2020Article
- Characterization of smooth muscle cells from human atherosclerotic lesions and their responses to Notch signaling.Laboratory investigation; a journal of technical methods and pathology · 2019Article
- HDAC6 Regulates the MRTF-A/SRF Axis and Vascular Smooth Muscle Cell Plasticity.JACC. Basic to translational science · 2018Article
- PI3Kγ promotes vascular smooth muscle cell phenotypic modulation and transplant arteriosclerosis via a SOX9-dependent mechanism.EBioMedicine · 2018Article
- Induced pluripotent stem cells with NOTCH1 gene mutation show impaired differentiation into smooth muscle and endothelial cells: Implications for bicuspid aortic valve-related aortopathy.The Journal of thoracic and cardiovascular surgery · 2018Article
- TGF-β Signaling in Control of Cardiovascular Function.Cold Spring Harbor perspectives in biology · 2018Review
- Global phosphoproteomic profiling reveals perturbed signaling in a mouse model of dilated cardiomyopathy.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- A class of their own: exploring the nondeacetylase roles of class IIa HDACs in cardiovascular disease.American journal of physiology. Heart and circulatory physiology · 2016Review
- Cell-cell contact and matrix adhesion promote αSMA expression during TGFβ1-induced epithelial-myofibroblast transition via Notch and MRTF-A.Scientific reports · 2016Article
- Identification of Histone Deacetylase 2 as a Functional Gene for Skeletal Muscle Development in Chickens.Asian-Australasian journal of animal sciences · 2016Article
- Origin and differentiation of vascular smooth muscle cells.The Journal of physiology · 2015Review
- Effect of HDAC Inhibitors on Corneal Keratocyte Mechanical Phenotypes in 3-D Collagen Matrices.Molecular vision · 2015Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundHistone deacetylases (HDACs) modify smooth muscle cell (SMC) proliferation and affect neointimal lesion formation by regulating cell cycle progression. HDACs might also regulate SMC differentiation, although this is not as well characterized. METHODS AND
resultsNotch signaling activates SMC contractile markers and the differentiated phenotype in human aortic SMCs. Using this model, we found that HDAC inhibition antagonized the ability of Notch to increase levels of smooth muscle α-actin, calponin1, smooth muscle 22α, and smooth muscle myosin heavy chain. However, inhibition of HDAC activity did not suppress Notch activation of the HRT target genes. In fact, HDAC inhibition increased activation of the canonical C-promoter binding factor-1 (CBF-1)-mediated Notch pathway, which activates HRT transcription. Although CBF-1-mediated Notch signaling was increased by HDAC inhibition in human SMCs and in a C3H10T1/2 model, SMC differentiation was inhibited in both cases. Further characterization of downstream Notch signaling pathways showed activation of the c-Jun N-terminal kinase, p38 mitogen-activated protein kinase, and PI3K/Akt pathways. The activation of these pathways was sensitive to HDAC inhibition and was positively correlated with the differentiated phenotype.
conclusionsOur studies define novel signaling pathways downstream of Notch signaling in human SMCs. In addition to the canonical CBF-1 pathway, Notch stimulates c-Jun N-terminal kinase, mitogen-activated protein kinase, and PI3K cascades. Both canonical and noncanonical pathways downstream of Notch promote a differentiated, contractile phenotype in SMCs. Although CBF-1-mediated Notch signaling is not suppressed by HDAC inhibition, HDAC activity is required for Notch differentiation signals through mitogen-activated protein kinase and PI3K pathways in SMCs. (J Am Heart Assoc. 2012;1:e000901 doi: 10.1161/JAHA.112.000901).
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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.