The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Clonal Hematopoiesis–Driver DNMT3A Mutations Alter Immune Cells in Heart Failure
Abstract
Rationale: Clonal hematopoiesis driven by mutations of DNMT3A (DNA methyltransferase 3a) is associated with increased incidence of cardiovascular disease and poor prognosis of patients with chronic heart failure (HF) and aortic stenosis. Although experimental studies suggest that DNMT3A clonal hematopoiesis–driver mutations may enhance inflammation, specific signatures of inflammatory cells in humans are missing. Objective: To define subsets of immune cells mediating inflammation in humans using single-cell RNA sequencing. Methods and Results: Transcriptomic profiles of peripheral blood mononuclear cells were analyzed in n=6 patients with HF harboring DNMT3A clonal hematopoiesis–driver mutations and n=4 patients with HF and no DNMT3A mutations by single-cell RNA sequencing. Monocytes of patients with HF carrying DNMT3A mutations demonstrated a significantly increased expression of inflammatory genes compared with monocytes derived from patients with HF without DNMT3A mutations. Among the specific upregulated genes were the prototypic inflammatory IL (interleukin) IL1B (interleukin 1B), IL6, IL8 , the inflammasome NLRP3 , and the macrophage inflammatory proteins CCL3 and CCL4 as well as resistin, which augments monocyte-endothelial adhesion. Silencing of DNMT3A in monocytes induced a paracrine proinflammatory activation and increased adhesion to endothelial cells. Furthermore, the classical monocyte subset of DNMT3A mutation carriers showed increased expression of T-cell stimulating immunoglobulin superfamily members CD300LB , CD83 , SIGLEC12 , as well as the CD2 ligand and cell adhesion molecule CD58 , all of which may be involved in monocyte–T-cell interactions. DNMT3A mutation carriers were further characterized by increased expression of the T-cell alpha receptor constant chain and changes in T helper cell 1, T helper cell 2, T helper cell 17, CD8+ effector, CD4+ memory, and regulatory T-cell–specific signatures. Conclusions: This study demonstrates that circulating monocytes and T cells of patients with HF harboring clonal hematopoiesis–driver mutations in DNMT3A exhibit a highly inflamed transcriptome, which may contribute to the aggravation of chronic HF.
Overview
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
Verification
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.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease
Ridker, P. M., Everett, B. M., Thuren, T., MacFadyen, J. G., Chang, W. H., Ballantyne, C., Fonseca, F., Nicolau, J., Koenig, W., Anker, S. D., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1707914 · Cited by 9,482
Age-related clonal hematopoiesis associated with adverse outcomes
Jaiswal, S., Fontanillas, P., Flannick, J., Manning, A., Grauman, P. V., Mar, B. G., Lindsley, R. C., Mermel, C. H., Burtt, N., Chavez, A., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1408617 · Cited by 4,841
Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease
Jaiswal, S., Natarajan, P., Silver, A. J., Gibson, C. J., Bick, A. G., Shvartz, E., McConkey, M., Gupta, N., Gabriel, S., Ardissino, D., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1701719 · Cited by 2,683
Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice
Fuster, J. J., MacLauchlan, S., Zuriaga, M. A., Polackal, M. N., Ostriker, A. C., Chakraborty, R., Wu, C.-L., Sano, S., Muralidharan, S., Rius, C., et al. (2017) · Science · doi:10.1126/science.aag1381 · Cited by 1,536
Clonal hematopoiesis in human aging and disease
Jaiswal, S., & Ebert, B. L. (2019) · Science · doi:10.1126/science.aan4673 · Cited by 1,156
Disruption of TET2 promotes the therapeutic efficacy of CD19-targeted T cells
Fraietta, J. A., Nobles, C. L., Sammons, M. A., Lundh, S., Carty, S. A., Reich, T. J., Cogdill, A. P., Morrissette, J. J. D., DeNizio, J. E., Reddy, S., et al. (2018) · Nature · doi:10.1038/s41586-018-0178-z · Cited by 862
De Novo Epigenetic Programs Inhibit PD-1 Blockade-Mediated T Cell Rejuvenation
Ghoneim, H. E., Fan, Y., Moustaki, A., Abdelsamed, H. A., Dash, P., Dogra, P., Carter, R., Awad, W., Neale, G., Thomas, P. G., et al. (2017) · Cell · doi:10.1016/j.cell.2017.06.007 · Cited by 781
The human heart contains distinct macrophage subsets with divergent origins and functions
Bajpai, G., Schneider, C., Wong, N., Bredemeyer, A., Hulsmans, M., Nahrendorf, M., Epelman, S., Kreisel, D., Liu, Y., Itoh, A., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0059-x · Cited by 712
Sano, S., Oshima, K., Wang, Y., MacLauchlan, S., Katanasaka, Y., Sano, M., Zuriaga, M. A., Yoshiyama, M., Goukassian, D., Cooper, M. A., et al. (2018) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2017.12.037 · Cited by 699
Dorsheimer, L., Assmus, B., Rasper, T., Ortmann, C. A., Ecke, A., Abou-El-Ardat, K., Schmid, T., Brüne, B., Wagner, S., Serve, H., et al. (2019) · JAMA Cardiology · doi:10.1001/jamacardio.2018.3965 · Cited by 470
Self-citation
Cited by
Inflammation, Aging, and Cardiovascular Disease
Liberale, L., Badimon, L., Montecucco, F., Lüscher, T. F., Libby, P., & Camici, G. G. (2022) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2021.12.017 · Cited by 462
Pascual-Figal, D. A., Bayes-Genis, A., Díez-Díez, M., Hernández-Vicente, Á., Vázquez-Andrés, D., de la Barrera, J., Vazquez, E., Quintas, A., Zuriaga, M. A., Asensio-López, M. C., et al. (2021) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2021.02.028 · Cited by 221
Clonal haematopoiesis and dysregulation of the immune system
Belizaire, R., Wong, W. J., Robinette, M. L., & Ebert, B. L. (2023) · Nature Reviews Immunology · doi:10.1038/s41577-023-00843-3 · Cited by 161
Clonal hematopoiesis: Mutation-specific adaptation to environmental change
Florez, M. A., Tran, B. T., Wathan, T. K., DeGregori, J., Pietras, E. M., & King, K. Y. (2022) · Cell Stem Cell · doi:10.1016/j.stem.2022.05.006 · Cited by 129
Clonal hematopoiesis in cardiovascular disease and therapeutic implications
Tall, A. R., & Fuster, J. J. (2022) · Nature Cardiovascular Research · doi:10.1038/s44161-021-00015-3 · Cited by 105
Metadata
- Authors
- Abplanalp, W. T., Cremer, S., John, D., Hoffmann, J., Schuhmacher, B., Merten, M., Rieger, M. A., Vasa-Nicotera, M., Zeiher, A. M., & Dimmeler, S.
- Venue
- Circulation Research
- Published
- 2021-01-22
- Volume
- 128
- Issue
- 2
- Pages
- 216-228
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W3097278438
- Cited by
- 257
- References
- 30
- FWCI
- 15.80
- Type
- journal article
- Language
- en
- Open access
- closed
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
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Clonal Hematopoiesis–Driver DNMT3A Mutations Alter Immune Cells in Heart Failure. https://app.cochat.ai/papers/10.1161/circresaha.120.317104
- The paper
- Abplanalp, W. T., Cremer, S., John, D., Hoffmann, J., Schuhmacher, B., Merten, M., Rieger, M. A., Vasa-Nicotera, M., Zeiher, A. M., & Dimmeler, S. (2021). Clonal Hematopoiesis–Driver DNMT3A Mutations Alter Immune Cells in Heart Failure. Circulation Research. https://doi.org/10.1161/circresaha.120.317104
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
