An HDAC9-MALAT1-BRG1 complex mediates smooth muscle dysfunction in thoracic aortic aneurysm
Open accessAbstract
Thoracic aortic aneurysm (TAA) has been associated with mutations affecting members of the TGF-β signaling pathway, or components and regulators of the vascular smooth muscle cell (VSMC) actomyosin cytoskeleton. Although both clinical groups present similar phenotypes, the existence of potential common mechanisms of pathogenesis remain obscure. Here we show that mutations affecting TGF-β signaling and VSMC cytoskeleton both lead to the formation of a ternary complex comprising the histone deacetylase HDAC9, the chromatin-remodeling enzyme BRG1, and the long noncoding RNA MALAT1. The HDAC9–MALAT1–BRG1 complex binds chromatin and represses contractile protein gene expression in association with gain of histone H3-lysine 27 trimethylation modifications. Disruption of Malat1 or Hdac9 restores contractile protein expression, improves aortic mural architecture, and inhibits experimental aneurysm growth. Thus, we highlight a shared epigenetic pathway responsible for VSMC dysfunction in both forms of TAA, with potential therapeutic implication for other known HDAC9-associated vascular diseases.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Non-coding RNAs also control VSMC plasticity, evidenced by the effect of specific miRNAs and long non-coding RNAs on VSMC biology and function.
“Non-coding RNAs also control VSMC plasticity 235,236 evidenced by the effect of specific miRNAs and long non-coding RNAs on VSMC biology and function 237,238 .”
From Vascular smooth muscle cells in atherosclerosis (2019) · cites this paper as [235]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 70 · Cited by 150
- Authors
- Lino Cardenas, C. L., Kessinger, C. W., Cheng, Y., MacDonald, C., MacGillivray, T., Ghoshhajra, B., Huleihel, L., Nuri, S., Yeri, A. S., Jaffer, F. A., Kaminski, N., Ellinor, P., Weintraub, N. L., Malhotra, R., Isselbacher, E. M., & Lindsay, M. E.
- Affiliations
- Harvard University (US)
- University of Pittsburgh (US)
- Yale University (US)
- Augusta University (US)
- Corresponding author
- Lindsay, Mark E.
- ORCID
- Venue
- Nature Communications
- Published
- 2018-03-08
- Volume
- 9
- Issue
- 1
- Pages
- 1009-1009
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC5843596
- OpenAlex
- W2793938361
- Cited by
- 150
- References
- 70
- Citations by year
- 2026: 13 · 2025: 13 · 2024: 15 · 2023: 17 · 2022: 18 · 2021: 22 · 2020: 22 · 2019: 24 · 2018: 6
- FWCI
- 11.35
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
- Funders
- National Heart, Lung, and Blood Institute (R01HL134354, R01HL112640, R01HL130113, R01HL126949, K08HL111210)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR070029)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Aortic Disease and Treatment Approaches
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Aortic aneurysm repair treatments
- Keywords
- thoracic aortic aneurysm, HDAC9, MALAT1, SMARCA4, long non-coding RNA, histone deacetylase, chromatin remodeling, vascular smooth muscle cells, TGF-beta signaling, actomyosin cytoskeleton, H3K27me3, epigenetic regulation, aneurysm pathogenesis
- MeSH terms
- Actomyosin, Animals, Aorta, Cell Line, Cell Nucleus, Chromatin, Disease Models, Animal, DNA Helicases, Female, Fluorescent Antibody Technique, Histone Deacetylases, Histones, Humans, Male, Muscle, Smooth, Vascular, Mutation, Nuclear Proteins, Phenotype, Repressor Proteins, Transcription Factors, Signal Transduction, Transforming Growth Factor beta, Aortic Aneurysm, Thoracic, Mice, Knockout, DNA Methylation, Myocytes, Smooth Muscle, RNA Interference, RNA, Small Interfering, Mice, Primary Cell Culture, RNA, Long Noncoding
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
