Unidirectional association of clonal hematopoiesis with atherosclerosis development.
Autor: | Díez-Díez M; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain., Ramos-Neble BL; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain., de la Barrera J; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain., Silla-Castro JC; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain., Quintas A; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain., Vázquez E; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain., Rey-Martín MA; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain., Izzi B; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain., Sánchez-García L; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain., García-Lunar I; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.; CIBER de Enfermedades Cardiovasculares, Madrid, Spain.; Cardiology Department, University Hospital La Moraleja, Madrid, Spain., Mendieta G; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.; Servicio de Cardiología, Institut Clínic Cardiovascular, Hospital Clínic de Barcelona, Barcelona, Spain.; Institut d'Investigacions Biomèdiques August Pi I Sunyer, Barcelona, Spain., Mass V; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain., Gómez-López N; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain., Espadas C; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain., González G; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain., Quesada AJ; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain., García-Álvarez A; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.; CIBER de Enfermedades Cardiovasculares, Madrid, Spain.; Servicio de Cardiología, Institut Clínic Cardiovascular, Hospital Clínic de Barcelona, Barcelona, Spain.; Institut d'Investigacions Biomèdiques August Pi I Sunyer, Barcelona, Spain.; Universitat de Barcelona, Barcelona, Spain., Fernández-Ortiz A; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.; CIBER de Enfermedades Cardiovasculares, Madrid, Spain.; Hospital Clínico San Carlos, Universidad Complutense, IdISSC, Madrid, Spain., Lara-Pezzi E; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.; CIBER de Enfermedades Cardiovasculares, Madrid, Spain., Dopazo A; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.; CIBER de Enfermedades Cardiovasculares, Madrid, Spain., Sánchez-Cabo F; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.; CIBER de Enfermedades Cardiovasculares, Madrid, Spain., Ibáñez B; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.; CIBER de Enfermedades Cardiovasculares, Madrid, Spain.; Cardiology Department, IIS-Fundación Jiménez Díaz University Hospital, Madrid, Spain., Andrés V; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.; CIBER de Enfermedades Cardiovasculares, Madrid, Spain., Fuster V; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain. vfuster@cnic.es.; Icahn School of Medicine at Mount Sinai, New York, NY, USA. vfuster@cnic.es., Fuster JJ; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain. jjfuster@cnic.es.; CIBER de Enfermedades Cardiovasculares, Madrid, Spain. jjfuster@cnic.es. |
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Jazyk: | angličtina |
Zdroj: | Nature medicine [Nat Med] 2024 Oct; Vol. 30 (10), pp. 2857-2866. Date of Electronic Publication: 2024 Aug 30. |
DOI: | 10.1038/s41591-024-03213-1 |
Abstrakt: | 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. (© 2024. The Author(s).) |
Databáze: | MEDLINE |
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