Unidirectional association of clonal hematopoiesis with atherosclerosis development
Clonal hematopoiesis, a condition in which acquired somatic mutations in hematopoietic stem cells lead to the outgrowth of a mutant hematopoietic clone, is associated with a higher risk of hematological cancer and a growing list of nonhematological disorders, most notably atherosclerosis and associated cardiovascular disease. However, whether accelerated atherosclerosis is a cause or a consequence of clonal hematopoiesis remains a matter of debate. Some studies support a direct contribution of certain clonal hematopoiesis-related mutations to atherosclerosis via exacerbation of inflammatory responses, whereas others suggest that clonal hematopoiesis is a symptom rather than a cause of atherosclerosis, as atherosclerosis or related traits may accelerate the expansion of mutant hematopoietic clones. Here we combine high-sensitivity DNA sequencing in blood and noninvasive vascular imaging to investigate the interplay between clonal hematopoiesis and atherosclerosis in a longitudinal cohort of healthy middle-aged individuals. We found that the presence of a clonal hematopoiesis-related mutation confers an increased risk of developing de novo femoral atherosclerosis over a 6-year period, whereas neither the presence nor the extent of atherosclerosis affects mutant cell expansion during this timeframe. These findings indicate that clonal hematopoiesis unidirectionally promotes atherosclerosis, which should help translate the growing understanding of this condition into strategies for the prevention of atherosclerotic cardiovascular disease in individuals exhibiting clonal hematopoiesis.
Authors
- Fátima Sánchez‐Cabo (ORCID: https://orcid.org/0000-0003-1881-1664)
- Ana García‐Álvarez (ORCID: https://orcid.org/0000-0002-1718-2424)
- Borja Ibáñez (ORCID: https://orcid.org/0000-0002-5036-254X)
- Guiomar Mendieta (ORCID: https://orcid.org/0000-0001-6652-9036)
- Jorge de la Barrera (ORCID: https://orcid.org/0000-0002-8138-6093)
- Juan Carlos Silla-Castro (ORCID: https://orcid.org/0000-0002-6058-5763)
- V. Fuster
- Beatriz L. Ramos-Neble (ORCID: https://orcid.org/0000-0003-1479-8490)
- Ana Dopazo (ORCID: https://orcid.org/0000-0002-4910-1684)
- Enrique Vázquez (ORCID: https://orcid.org/0000-0003-1157-2592)
- Ana Quintas (ORCID: https://orcid.org/0000-0003-3721-7580)
- Antonio Fernández‐Ortíz (ORCID: https://orcid.org/0000-0002-3239-1910)
- M. Ascensión Rey-Martín
- Vicente Andrés (ORCID: https://orcid.org/0000-0002-0125-7209)
- Inés García‐Lunar (ORCID: https://orcid.org/0000-0003-4117-6814)
- Lucía Sánchez-García
- Enrique Lara‐Pezzi (ORCID: https://orcid.org/0000-0002-2743-1033)
- Miriam Díez-Díez (ORCID: https://orcid.org/0000-0003-1945-825X)
- Benedetta Izzi (ORCID: https://orcid.org/0000-0002-3649-7931)
- Virginia Mass
- José J. Fuster (ORCID: https://orcid.org/0000-0002-5970-629X)
- Cristina Espadas (ORCID: https://orcid.org/0000-0003-1794-0691)
- Antonio J. Quesada (ORCID: https://orcid.org/0000-0002-3280-8819)
- Gema González
- Nuria Gómez-López
Institutions
- Spanish National Centre for Cardiovascular Research (ES)
- Hospital Clínico San Carlos (ES)
- Centro de Investigación en Red en Enfermedades Cardiovasculares (ES)
- Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (ES)
- Hospital Clínic de Barcelona (ES)
- Hospital Universitario Fundación Jiménez Díaz (ES)
- Spanish National Centre for Cardiovascular Research (ES)
- Hospital General de La Rioja (ES)
- Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES)
- Hospital Universitario Sanitas La Moraleja (ES)
- Universitat de Barcelona (ES)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- Nature Medicine
- Published
- 2024-08-30
- DOI
- https://doi.org/10.1038/s41591-024-03213-1
- Citations
- 60
- Primary Topic
- Acute Myeloid Leukemia Research
- Type
- article
- Field-Weighted Citation Impact
- 27.26
Funders
- Banco Santander
- Comunidad de Madrid
- Ministerio de Ciencia, Innovación y Universidades
- European Commission
- Ministerio de Ciencia e Innovación
- Centro Nacional de Investigaciones Cardiovasculares
- Horizon 2020 Framework Programme
- Instituto de Salud Carlos III
- European Regional Development Fund
- Agencia Estatal de Investigación
- European Social Fund