Evidence map›Paper›PMID 37942611›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2024

FAM222A, Part of the BET-Regulated Basal Endothelial Transcriptome, Is a Novel Determinant of Endothelial Biology and Angiogenesis-Brief Report.

Aspasia Tzani, Stefan Haemmig, Henry S Cheng, Daniel Pérez-Cremades, Marina Augusto Heuschkel, Anurag Jamaiyar, Sasha A Singh, Masanori Aikawa, Paul B Yu, Tianxi Wang and 3 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.6field-weighted citation impact, top 29% 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

5 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Advances in nucleic acid delivery strategies for diabetic wound therapy.Journal of clinical & translational endocrinology · 2024
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 2 institutions in 1 country.

Aspasia TzaniDivision of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.T., S.H., H.S.C., D.P.-C., M.A.H., A.J., S.A.S., M.A., P.B.Y., M.W.F., J.P.).
Stefan HaemmigDivision of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.T., S.H., H.S.C., D.P.-C., M.A.H., A.J., S.A.S., M.A., P.B.Y., M.W.F., J.P.).
Henry S ChengDivision of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.T., S.H., H.S.C., D.P.-C., M.A.H., A.J., S.A.S., M.A., P.B.Y., M.W.F., J.P.).ORCID 0000-0002-4254-962X
Daniel Pérez-CremadesDivision of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.T., S.H., H.S.C., D.P.-C., M.A.H., A.J., S.A.S., M.A., P.B.Y., M.W.F., J.P.).ORCID 0000-0002-0969-8762
Marina Augusto HeuschkelDivision of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.T., S.H., H.S.C., D.P.-C., M.A.H., A.J., S.A.S., M.A., P.B.Y., M.W.F., J.P.).
Anurag JamaiyarDivision of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.T., S.H., H.S.C., D.P.-C., M.A.H., A.J., S.A.S., M.A., P.B.Y., M.W.F., J.P.).ORCID 0000-0002-8731-2394
Sasha A SinghDivision of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.T., S.H., H.S.C., D.P.-C., M.A.H., A.J., S.A.S., M.A., P.B.Y., M.W.F., J.P.).ORCID 0000-0003-0929-3164
Masanori AikawaDivision of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.T., S.H., H.S.C., D.P.-C., M.A.H., A.J., S.A.S., M.A., P.B.Y., M.W.F., J.P.).ORCID 0000-0002-9275-2079
Paul B YuDivision of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.T., S.H., H.S.C., D.P.-C., M.A.H., A.J., S.A.S., M.A., P.B.Y., M.W.F., J.P.).ORCID 0000-0003-2145-4944
Tianxi WangDepartment of Ophthalmology, Boston Children's Hospital, MA (T.W., Y.S.).ORCID 0000-0001-8152-3273
Ye SunDepartment of Ophthalmology, Boston Children's Hospital, MA (T.W., Y.S.).ORCID 0000-0002-7674-9056
Mark W FeinbergDivision of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.T., S.H., H.S.C., D.P.-C., M.A.H., A.J., S.A.S., M.A., P.B.Y., M.W.F., J.P.).ORCID 0000-0001-9523-3859
Jorge PlutzkyDivision of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.T., S.H., H.S.C., D.P.-C., M.A.H., A.J., S.A.S., M.A., P.B.Y., M.W.F., J.P.).ORCID 0000-0002-7194-9876
Brigham and Women's Hospital · USBoston Children's Hospital · US

Funding

Tissue AnalysesP01HL048743 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI GLADYSHEV, VADIM N. · 1992 to 2014
$26.3M
Photoreceptor Determination of Retinal Blood Vessel Growth in RetinopathyR01EY029238 · NEI · BOSTON CHILDREN'S HOSPITAL · PI YE SUN · 2019 to 2026
$2.6M
ALDH1a1 Inhibition As A Therapeutic Target In Visceral Adiposity and Type 2 DiabetesR01DK107239 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI GRIFFIN, PATRICK ROBERT, PLUTZKY, JORGE · 2017 to 2021
$2.5M
Context-specific angiogenic signaling in the pulmonary vasculatureR01HL159443 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI YU, PAUL B · 2021 to 2024
$2.4M
The Mechanism of Immune-Vascular Crosstalk in RetinopathyR01EY030140 · NEI · BOSTON CHILDREN'S HOSPITAL · PI SUN, YE · 2019 to 2023
$2.0M
Epigenetic Control of Endothelial and T Cell States By BET Reader ProteinsR56HL125894 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI PLUTZKY, JORGE · 2015 to 2015
$429k
NEI NIH HHS R01 EY029238NEI NIH HHS R01 EY030140NHLBI NIH HHS P01 HL048743NHLBI NIH HHS R01 HL159443NHLBI NIH HHS R56 HL125894NIDDK NIH HHS R01 DK107239
6 · The paper itself

Abstract

backgroundBETs (bromodomain and extraterminal domain-containing epigenetic reader proteins), including BRD4 (bromodomain-containing protein 4), orchestrate transcriptional programs induced by pathogenic stimuli, as intensively studied in cardiovascular disease and elsewhere. In endothelial cells (ECs), BRD4 directs induced proinflammatory, proatherosclerotic transcriptional responses; BET inhibitors, like JQ1, repress these effects and decrease atherosclerosis. While BET effects in pathogenic conditions have prompted therapeutic BET inhibitor development, BET action under basal conditions, including ECs, has remained understudied. To understand BET action in basal endothelial transcriptional programs, we first analyzed EC RNA-Seq data in the absence versus presence of JQ1 before using BET regulation to identify novel determinants of EC biology and function.

methodsRNA-Seq datasets of human umbilical vein ECs without and with JQ1 treatment were analyzed. After identifying C12orf34, also known as FAM222A (family with sequence similarity 222 member A), as a previously unreported, basally expressed, potently JQ1-induced EC gene, FAM222A was studied in endothelial and angiogenic responses in vitro using small-interference RNA silencing and lentiviral overexpression, in vitro, ex vivo and in vivo, including aortic sprouting, matrigel plug assays, and murine neonatal oxygen-induced retinopathy.

resultsResting EC RNA-Seq data indicate BETs direct transcriptional programs underlying core endothelial properties including migration, proliferation, and angiogenesis. BET inhibition in resting ECs also significantly induced a subset of mRNAs, including FAM222A-a unique BRD4-regulated gene with no reported EC role. Silencing endothelial FAM222A significantly decreased cellular proliferation, migration, network formation, aorta sprouting, and Matrigel plug vascularization through coordinated modulation of VEGF (vascular endothelial growth factor) and NOTCH mediator expression in vitro, ex vivo, in vivo; lentiviral FAM222A overexpression had opposite effects. In vivo, siFAM222A significantly repressed retinal revascularization in neonatal murine oxygen-induced retinopathy through similar angiogenic signaling modulation.

conclusionsBET control over the basal endothelial transcriptome includes FAM222A, a novel, BRD4-regulated, key determinant of endothelial biology and angiogenesis.

Indexed as

Retinal DiseasesTranscription FactorsAmyloidogenic ProteinsAngiogenesisAnimalsBiologyBromodomain Containing ProteinsCell Cycle ProteinsHumansHuman Umbilical Vein Endothelial CellsMiceNerve Tissue ProteinsNuclear ProteinsOxygenTranscriptomeVascular Endothelial Growth Factor AAmyloidogenic ProteinsBRD4 protein, humanBromodomain Containing ProteinsCell Cycle ProteinsFAM222A protein, humanFam222a protein, mouseNerve Tissue ProteinsNuclear ProteinsOxygenTranscription FactorsVascular Endothelial Growth Factor Aangiogenesisbromodomain-containing proteinsendothelial cellsendotheliumepigeneticsretinopathy of prematurity

Identifiers

PMID37942611
PMCPMC10840377
OpenAlexW4388532914

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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.