The DOI matches its Crossref record; 64 of the 64 references it cites were found in a registry or an index.
Increased stem cell proliferation in atherosclerosis accelerates clonal hematopoiesis
Open accessAbstract
Clonal hematopoiesis, a condition in which individual hematopoietic stem cell clones generate a disproportionate fraction of blood leukocytes, correlates with higher risk for cardiovascular disease. The mechanisms behind this association are incompletely understood. Here, we show that hematopoietic stem cell division rates are increased in mice and humans with atherosclerosis. Mathematical analysis demonstrates that increased stem cell proliferation expedites somatic evolution and expansion of clones with driver mutations. The experimentally determined division rate elevation in atherosclerosis patients is sufficient to produce a 3.5-fold increased risk of clonal hematopoiesis by age 70. We confirm the accuracy of our theoretical framework in mouse models of atherosclerosis and sleep fragmentation by showing that expansion of competitively transplanted Tet2-/- cells is accelerated under conditions of chronically elevated hematopoietic activity. Hence, increased hematopoietic stem cell proliferation is an important factor contributing to the association between cardiovascular disease and clonal hematopoiesis.
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“These cytokines display overlapping features, such as inducing cell cycle entry of HSCs and their differentiation, frequently toward the granulo-monocytic lineage 1,4-6,12-15 .”
From Type 1 interferon perturbates clonal competition by reshaping human blood development (2026) · cites this paper as [5]
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“While clonal expansion during normal ageing has not yet been observed in mice, it has been reported in mouse models for disease61 and in physiologically aged macaques62.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [61]
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“The disease process itself has been suggested to reciprocally accelerate CH [41] (Figure 1).”
From Clonal hematopoiesis and inflammation – the perpetual cycle (2023) · cites this paper as [41]
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In the citing paper
“The isolated effects of individual inflammatory cytokines, including type 1 interferons (IFNa/b) 1-3 , type 2 IFN (IFNg) 4-6 , TNFa 7,8 , and IL-1 9-11 , have been well-documented in mouse hematopoietic development.”
From Type 1 interferon perturbates clonal competition by reshaping human blood development (2026) · cites this paper as [5]
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Citations
Cites
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 blood-cancer risk inferred from blood DNA sequence
Genovese, G., Kähler, A. K., Handsaker, R. E., Lindberg, J., Rose, S. A., Bakhoum, S. F., Chambert, K., Mick, E., Neale, B. M., Fromer, M., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1409405 · Cited by 3,531
Fate Mapping Reveals Origins and Dynamics of Monocytes and Tissue Macrophages under Homeostasis
Yona, S., Kim, K.-W., Wolf, Y., Mildner, A., Varol, D., Breker, M., Strauss-Ayali, D., Viukov, S., Guilliams, M., Misharin, A., et al. (2013) · Immunity · doi:10.1016/j.immuni.2012.12.001 · Cited by 3,245
Kiel, M. J., Yilmaz, Ö. H., Iwashita, T., Yilmaz, O. H., Terhorst, C., & Morrison, S. J. (2005) · Cell · doi:10.1016/j.cell.2005.05.026 · Cited by 3,168
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
Evolutionary Dynamics: Exploring the Equations of Life
NOWAK, M. A. (2006) · doi:10.2307/j.ctvjghw98 · Cited by 2,438
Self-citationClonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes
Steensma, D. P., Bejar, R., Jaiswal, S., Lindsley, R. C., Sekeres, M. A., Hasserjian, R. P., & Ebert, B. L. (2015) · Blood · doi:10.1182/blood-2015-03-631747 · Cited by 1,971
Age-related mutations associated with clonal hematopoietic expansion and malignancies
Xie, M., Lu, C., Wang, J., McLellan, M. D., Johnson, K. J., Wendl, M. C., McMichael, J. F., Schmidt, H. K., Yellapantula, V., Miller, C. A., et al. (2014) · Nature Medicine · doi:10.1038/nm.3733 · Cited by 1,874
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
Tacke, F., Alvarez, D., Kaplan, T. J., Jakubzick, C., Spanbroek, R., Llodra, J., Garin, A., Liu, J., Mack, M., van Rooijen, N., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci28549 · Cited by 1,323
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Atherosclerosis: Recent developments
Björkegren, J., & Lusis, A. J. (2022) · Cell · doi:10.1016/j.cell.2022.04.004 · Cited by 1,344
Targeting inflammation in atherosclerosis — from experimental insights to the clinic
Soehnlein, O., & Libby, P. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00198-1 · Cited by 1,085
Social Determinants of Cardiovascular Disease
Powell‐Wiley, T. M., Baumer, Y., Baah, F. O., Baez, A. S., Farmer, N., Mahlobo, C. T., Pita, M. A., Potharaju, K. A., Tamura, K., & Wallen, G. R. (2022) · Circulation Research · doi:10.1161/circresaha.121.319811 · Cited by 934
Ageing and rejuvenation of tissue stem cells and their niches
Brunet, A., Goodell, M. A., & Rando, T. A. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00510-w · Cited by 407
Atherosclerosis and Inflammation: Insights from the Theory of General Pathological Processes
Gusev, E., & Sarapultsev, A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24097910 · Cited by 357
Metadata
- Authors
- Heyde, A., Rohde, D., McAlpine, C. S., Zhang, S., Hoyer, F. F., Gerold, J. M., Cheek, D., Iwamoto, Y., Schloss, M. J., Vandoorne, K., Iborra-Egea, O., Muñoz-Guijosa, C., Bayes-Genis, A., Reiter, J. G., Craig, M., Swirski, F. K., Nahrendorf, M., Nowak, M. A., & Naxerova, K.
- Affiliations
- Harvard University (US)
- Hospital Universitari Germans Trias i Pujol (ES)
- Stanford University (US)
- Centre Hospitalier Universitaire Sainte-Justine (CA)
- Corresponding author
- Naxerova, Kamila
- ORCID
- Heyde, Alexander
- Rohde, David
- McAlpine, Cameron S.
- Zhang, Shuang
- Hoyer, Friedrich F.
- Gerold, Jeffrey M.
- Cheek, David
- Iwamoto, Yoshiko
- Schloss, Maximilian J.
- Vandoorne, Katrien
- Iborra-Egea, Oriol
- Muñoz-Guijosa, Christian
- Reiter, Johannes G.
- Craig, Morgan
- Swirski, Filip K.
- Nahrendorf, Matthias
- Nowak, Martin A.
- Naxerova, Kamila
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2021-03
- Volume
- 184
- Issue
- 5
- Pages
- 1348-1361.e22
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC8109274
- OpenAlex
- W3130296909
- Cited by
- 267
- References
- 64
- Citations by year
- 2026: 33 · 2025: 48 · 2024: 45 · 2023: 47 · 2022: 61 · 2021: 33
- FWCI
- 31.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 368 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Science Foundation
- National Heart, Lung, and Blood Institute
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- clonal hematopoiesis, atherosclerosis, hematopoietic stem cell proliferation, somatic evolution, driver mutations, cardiovascular risk, TET2, sleep fragmentation, hematopoietic stem cell transplantation
- MeSH terms
- Clonal Hematopoiesis, Aging, Animals, Apolipoproteins E, Bone Marrow, Disease Models, Animal, Female, Hematopoietic Stem Cells, Humans, Mice, Inbred C57BL, Models, Biological, Sleep Deprivation, Cell Proliferation, Atherosclerosis, Mice, Clonal Evolution
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