Lamin A/C Expression in Hematopoietic Cells Declines During Human Aging and Constrains Atherosclerosis in Mice
dc.contributor.author | Amorós Pérez, Marta | |
dc.contributor.author | Moreno Muñoz, Guillermo | |
dc.contributor.author | González Granado, José María | |
dc.contributor.author | Bueno Zamora, Héctor José | |
dc.contributor.author | Fuster, José J. | |
dc.contributor.author | Andrés, Vicente | |
dc.date.accessioned | 2025-07-08T12:20:44Z | |
dc.date.available | 2025-07-08T12:20:44Z | |
dc.date.issued | 2025-07-03 | |
dc.description.abstract | Background: Aging is the primary risk factor for atherosclerosis, a degenerative process regulated by immune cells and the leading cause of death worldwide. Previous studies on premature aging syndromes have linked atherosclerosis to defects in A-type lamins, key nuclear envelope components. However, whether these defects influence atherosclerosis during normal aging remains unexplored. Here, we examined how aging affects lamin A/C expression in circulating leukocytes and investigated the impact of manipulating their expression in hematopoietic cells on their function and atherosclerosis progression. Methods: Flow cytometry assessed lamin A/C expression in human circulating leukocytes. Bone marrow from donor mice was transplanted into lethally irradiated, Ldlr-/--deficient mice to study leukocyte extravasation into the vessel wall via intravital microscopy in the cremaster muscle, and high-fat-diet-induced atherosclerosis via Oil Red O staining of the aorta and carotid arteries. Single-cell RNA sequencing of the aorta was conducted to identify transcriptional changes associated with hematopoietic cell lamin A/C gain-of-function or loss-of-function. Results: Human aging is associated with lower levels of lamin A/C expression in blood-borne leukocytes. To evaluate the functional relationship between hematopoietic lamin A/C expression and atherosclerosis development, we used Lmna-null mice and Lmnatg mice, the latter being the first in vivo model of lamin A gain-of-function. Transplanting lamin A/C-deficient bone marrow into Ldlr-/- mice increased leukocyte extravasation into the vessel wall and accelerated atherosclerosis. Conversely, transplantation of bone marrow overexpressing lamin A into Ldlr-/- receptor mice reduced leukocyte extravasation and atherosclerosis. Single-cell RNA sequencing of atherosclerotic mouse aorta revealed that alterations to hematopoietic cell lamin A/C expression primarily modify the transcriptome of immune cell populations and endothelial cells, affecting their functionality. Conclusions: We suggest that the age-related decline in lamin A/C expression in blood-borne immune cells contributes to increased leukocyte extravasation and atherosclerosis, highlighting lamin A/C as a novel regulator of age-related atherosclerosis. | |
dc.description.department | Depto. de Inmunología, Oftalmología y ORL | |
dc.description.faculty | Fac. de Medicina | |
dc.description.refereed | TRUE | |
dc.description.status | inpress | |
dc.identifier.citation | Amorós-Pérez, M., Del Monte-Monge, A., Gonzalo, P., Andrés-Manzano, M. J., Rius, C., Fanjul, V., González-Gómez, C., Moreno, G., Benguria, A., Dopazo, A., Sanchez-Cabo, F., Torroja, C., Martínez de Benito, F., Calì, B., Vargas, P., Silvestre-Roig, C., González-Granado, J. M., Bueno, H., Fuster, J. J., & Andrés, V. (2025). Lamin A/C Expression in Hematopoietic Cells Declines During Human Aging and Constrains Atherosclerosis in Mice. Arteriosclerosis, thrombosis, and vascular biology, 10.1161/ATVBAHA.124.322893. Advance online publication. https://doi.org/10.1161/ATVBAHA.124.322893 | |
dc.identifier.doi | 10.1161/ATVBAHA.124.322893 | |
dc.identifier.essn | 1524-4636 | |
dc.identifier.issn | 1079-5642 | |
dc.identifier.officialurl | https://doi.org/10.1161/ATVBAHA.124.322893 | |
dc.identifier.pmid | 40605747 | |
dc.identifier.relatedurl | https://www.ahajournals.org/doi/10.1161/ATVBAHA.124.322893 | |
dc.identifier.uri | https://hdl.handle.net/20.500.14352/122328 | |
dc.journal.title | Arterioscler, Thrombosis and Vascular Biology | |
dc.language.iso | eng | |
dc.publisher | American Heart Association | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | en |
dc.rights.accessRights | open access | |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.subject.cdu | 616.15 | |
dc.subject.keyword | aging | |
dc.subject.keyword | atherosclerosis | |
dc.subject.keyword | cardiovascular diseases | |
dc.subject.keyword | inflammation | |
dc.subject.keyword | nuclear lamina | |
dc.subject.ucm | Ciencias Biomédicas | |
dc.subject.unesco | 24 Ciencias de la Vida | |
dc.title | Lamin A/C Expression in Hematopoietic Cells Declines During Human Aging and Constrains Atherosclerosis in Mice | |
dc.type | journal article | |
dc.type.hasVersion | VoR | |
dspace.entity.type | Publication | |
relation.isAuthorOfPublication | 907be5df-d04d-42bd-9427-258b71326fb6 | |
relation.isAuthorOfPublication | 2454c553-f99d-4279-a652-540e815a9520 | |
relation.isAuthorOfPublication | 4157a247-4f43-4ba2-a74b-3abb8baf6b20 | |
relation.isAuthorOfPublication.latestForDiscovery | 2454c553-f99d-4279-a652-540e815a9520 |
Download
Original bundle
1 - 1 of 1
Loading...
- Name:
- Lamin AC Expression in Hematopoietic Cells.pdf
- Size:
- 3.98 MB
- Format:
- Adobe Portable Document Format