Evidence map›Paper›PMID 35502657›Full record

ArticleCirculation2022

Histone Acetyltransferases p300 and CBP Coordinate Distinct Chromatin Remodeling Programs in Vascular Smooth Muscle Plasticity.

Raja Chakraborty, Allison C Ostriker, Yi Xie, Jui M Dave, Ana Gamez-Mendez, Payel Chatterjee, Yaw Abu, Jake Valentine, Kimberly Lezon-Geyda, Daniel M Greif and 5 more

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In one paragraph

Article in Circulation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed
8.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

69 citing papers in PubMed, 101 citations in OpenAlex.

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9 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 2 institutions in 2 countries.

Raja ChakrabortyDepartments of Medicine (Cardiovascular Medicine) (R.C., A.C.O., Y.X., J.M.D., P.C., Y.A., J.V., D.M.G., J.H., K.A.M), Yale University School of Medicine, New Haven, CT.
Allison C OstrikerDepartments of Medicine (Cardiovascular Medicine) (R.C., A.C.O., Y.X., J.M.D., P.C., Y.A., J.V., D.M.G., J.H., K.A.M), Yale University School of Medicine, New Haven, CT.
Yi XieDepartments of Medicine (Cardiovascular Medicine) (R.C., A.C.O., Y.X., J.M.D., P.C., Y.A., J.V., D.M.G., J.H., K.A.M), Yale University School of Medicine, New Haven, CT.ORCID 0000-0002-2641-5859
Jui M DaveDepartments of Medicine (Cardiovascular Medicine) (R.C., A.C.O., Y.X., J.M.D., P.C., Y.A., J.V., D.M.G., J.H., K.A.M), Yale University School of Medicine, New Haven, CT.
Ana Gamez-MendezPharmacology (R.C., A.C.O., Y.X., A.G.-M., P.C., Y.A., J.V., W.C.S., K.A.M.), Yale University School of Medicine, New Haven, CT.
Payel ChatterjeeDepartments of Medicine (Cardiovascular Medicine) (R.C., A.C.O., Y.X., J.M.D., P.C., Y.A., J.V., D.M.G., J.H., K.A.M), Yale University School of Medicine, New Haven, CT.
Yaw AbuDepartments of Medicine (Cardiovascular Medicine) (R.C., A.C.O., Y.X., J.M.D., P.C., Y.A., J.V., D.M.G., J.H., K.A.M), Yale University School of Medicine, New Haven, CT.
Jake ValentineDepartments of Medicine (Cardiovascular Medicine) (R.C., A.C.O., Y.X., J.M.D., P.C., Y.A., J.V., D.M.G., J.H., K.A.M), Yale University School of Medicine, New Haven, CT.
Kimberly Lezon-GeydaPediatrics (K.L.-G., V.P.S., P.G.G.), Yale University School of Medicine, New Haven, CT.ORCID 0000-0002-1958-0354
Daniel M GreifDepartments of Medicine (Cardiovascular Medicine) (R.C., A.C.O., Y.X., J.M.D., P.C., Y.A., J.V., D.M.G., J.H., K.A.M), Yale University School of Medicine, New Haven, CT.
Vincent P SchulzPediatrics (K.L.-G., V.P.S., P.G.G.), Yale University School of Medicine, New Haven, CT.
Patrick G GallagherGenetics (J.M.D., D.M.G., P.G.G.), Yale University School of Medicine, New Haven, CT.
William C SessaPharmacology (R.C., A.C.O., Y.X., A.G.-M., P.C., Y.A., J.V., W.C.S., K.A.M.), Yale University School of Medicine, New Haven, CT.ORCID 0000-0001-5759-1938
John HwaDepartments of Medicine (Cardiovascular Medicine) (R.C., A.C.O., Y.X., J.M.D., P.C., Y.A., J.V., D.M.G., J.H., K.A.M), Yale University School of Medicine, New Haven, CT.ORCID 0000-0001-7366-2628
Kathleen A MartinDepartments of Medicine (Cardiovascular Medicine) (R.C., A.C.O., Y.X., J.M.D., P.C., Y.A., J.V., D.M.G., J.H., K.A.M), Yale University School of Medicine, New Haven, CT.ORCID 0000-0002-1748-0034
Yale University · USCardiovascular Research Center · BR

Funding

Novel vascular smooth muscle cell progenitors in development and diseaseR35HL150766 · NHLBI · YALE UNIVERSITY · PI Daniel Greif · 2020 to 2026
$7.0M
Hyperglycemia, thromboxane and platelet activity in diabetes mellitusR01HL115247 · NHLBI · YALE UNIVERSITY · PI HWA, JOHN · 2012 to 2019
$3.8M
Novel insights into intimal hyperplasia in cardiac allograft vasculopathyR01HL142090 · NHLBI · YALE UNIVERSITY · PI MARTIN, KATHLEEN ANN · 2018 to 2021
$2.4M
Platelets in vascular injury repairR01HL150515 · NHLBI · YALE UNIVERSITY · PI HWA, JOHN · 2020 to 2023
$2.3M
Role of LMO7 in atherosclerosisR01HL151222 · NHLBI · YALE UNIVERSITY · PI MARTIN, KATHLEEN ANN · 2020 to 2023
$2.2M
Coordinated regulation of vascular smooth muscle phenotype by p300, CBP, and TET2R01HL146101 · NHLBI · YALE UNIVERSITY · PI GALLAGHER, PATRICK G, MARTIN, KATHLEEN ANN · 2019 to 2022
$2.2M
Smooth muscle progenitors in vascular remodelingR01HL133016 · NHLBI · YALE UNIVERSITY · PI GREIF, DANIEL · 2016 to 2019
$1.7M
Epigenetic control of vascular smooth muscle in cardiovascular diseaseR01HL119529 · NHLBI · YALE UNIVERSITY · PI MARTIN, KATHLEEN ANN · 2014 to 2017
$1.7M
Vascular disease pathogenesis: the interface of smooth muscle and immune cellsR01HL142674 · NHLBI · YALE UNIVERSITY · PI GREIF, DANIEL · 2018 to 2019
$1.1M
Aging and clonality in atherosclerosisR21AG062202 · NIA · YALE UNIVERSITY · PI FERNANDEZ HERNANDO, CARLOS, GREIF, DANIEL · 2019 to 2020
$461k
NHLBI NIH HHS R01 HL115247NHLBI NIH HHS R01 HL119529NHLBI NIH HHS R01 HL133016NHLBI NIH HHS R01 HL142090NHLBI NIH HHS R01 HL142674NHLBI NIH HHS R01 HL146101NHLBI NIH HHS R01 HL150515NHLBI NIH HHS R01 HL151222NHLBI NIH HHS R35 HL150766NIA NIH HHS R21 AG062202
6 · The paper itself

Abstract

backgroundVascular smooth muscle cell (VSMC) phenotypic switching contributes to cardiovascular diseases. Epigenetic regulation is emerging as a key regulatory mechanism, with the methylcytosine dioxygenase TET2 acting as a master regulator of smooth muscle cell phenotype. The histone acetyl-transferases p300 and CREB-binding protein (CBP) are highly homologous and often considered to be interchangeable, and their roles in smooth muscle cell phenotypic regulation are not known.

methodsWe assessed the roles of p300 and CBP in human VSMC with knockdown, in inducible smooth muscle-specific knockout mice (inducible knockout [iKO];

resultsP300, CBP, and histone acetylation were differently regulated in VSMCs undergoing phenotypic switching and in vessel remodeling after vascular injury. Medial p300 expression and activity were repressed by injury, but CBP and histone acetylation were induced in neointima. Knockdown experiments revealed opposing effects of p300 and CBP in the VSMC phenotype: p300 promoted contractile protein expression and inhibited migration, but CBP inhibited contractile genes and enhanced migration. p300

conclusionsThis work reveals that p300 and CBP serve nonredundant and opposing functions in VSMC phenotypic switching and coordinately regulate chromatin modifications through distinct functional interactions with TET2 or HDACs. Targeting specific histone acetyl-transferases may hold therapeutic promise for cardiovascular diseases.

Indexed as

Cardiovascular DiseasesMuscle, Smooth, VascularAcetylationAnimalsChromatin Assembly and DisassemblyContractile ProteinsCREB-Binding ProteinEpigenesis, GeneticHistonesHumansHyperplasiaMiceMice, KnockoutMyocytes, Smooth Musclep300-CBP Transcription FactorsContractile ProteinsCREB-Binding ProteinHistonesp300-CBP Transcription Factorsacetylationchromatin remodelingepigeneticshistone acetyltransferaseshyperplasiasmooth muscle cells

Identifiers

PMID35502657
PMCPMC12047542
OpenAlexW4225414547

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Registered trials

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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.