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TP53-mediated clona...
TP53-mediated clonal hematopoiesis confers increased risk for incident atherosclerotic disease
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- Zekavat, Seyedeh M. (författare)
- Broad Institute,Yale University,Massachusetts Eye and Ear Infirmary
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- Viana-Huete, Vanesa (författare)
- Centro Nacional de Investigaciones Cardiovasculares Carlos III
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- Matesanz, Nuria (författare)
- Centro Nacional de Investigaciones Cardiovasculares Carlos III
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- Jorshery, Saman Doroodgar (författare)
- Massachusetts Institute of Technology
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- Zuriaga, María A. (författare)
- Centro Nacional de Investigaciones Cardiovasculares Carlos III
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- Uddin, Md Mesbah (författare)
- Massachusetts General Hospital,Broad Institute
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- Trinder, Mark (författare)
- University of British Columbia,Massachusetts General Hospital,Broad Institute
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- Paruchuri, Kaavya (författare)
- Massachusetts General Hospital,Harvard Medical School,Broad Institute
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- Zorita, Virginia (författare)
- Centro Nacional de Investigaciones Cardiovasculares Carlos III
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- Ferrer-Pérez, Alba (författare)
- Centro Nacional de Investigaciones Cardiovasculares Carlos III
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- Amorós-Pérez, Marta (författare)
- Centro Nacional de Investigaciones Cardiovasculares Carlos III
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- Kunderfranco, Paolo (författare)
- Humanitas Research Hospital
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- Carriero, Roberta (författare)
- Humanitas Research Hospital
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- Greco, Carolina M. (författare)
- Humanitas University,Humanitas Research Hospital
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- Aroca-Crevillen, Alejandra (författare)
- Centro Nacional de Investigaciones Cardiovasculares Carlos III
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- Hidalgo, Andrés (författare)
- Yale University,Centro Nacional de Investigaciones Cardiovasculares Carlos III
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- Damrauer, Scott M. (författare)
- University of Pennsylvania,Veterans Health Administration
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- Ballantyne, Christie M. (författare)
- Baylor College of Medicine
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- Niroula, Abhishek (författare)
- Lund University,Lunds universitet,Hematogenomics,Forskargrupper vid Lunds universitet,Lund University Research Groups,Broad Institute,Dana-Farber Cancer Institute
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- Gibson, Christopher J. (författare)
- Dana-Farber Cancer Institute
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- Pirruccello, James (författare)
- Broad Institute,University of California, San Francisco,Massachusetts General Hospital
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- Griffin, Gabriel (författare)
- Broad Institute,Brigham and Women's Hospital / Harvard Medical School,Dana-Farber Cancer Institute
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- Ebert, Benjamin L. (författare)
- Howard Hughes Medical Institute,Dana-Farber Cancer Institute
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- Libby, Peter (författare)
- Brigham and Women's Hospital / Harvard Medical School
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- Fuster, Valentín (författare)
- Centro Nacional de Investigaciones Cardiovasculares Carlos III,Icahn School of Medicine at Mount Sinai
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- Zhao, Hongyu (författare)
- Yale University
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- Ghassemi, Marzyeh (författare)
- Massachusetts Institute of Technology
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- Natarajan, Pradeep (författare)
- Harvard Medical School,Broad Institute,Massachusetts General Hospital
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- Bick, Alexander G. (författare)
- Vanderbilt University
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- Fuster, José J. (författare)
- Centro Nacional de Investigaciones Cardiovasculares Carlos III
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- Klarin, Derek (författare)
- VA Palo Alto Health Care System,Stanford University School of Medicine
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(creator_code:org_t)
- 2023-01-16
- 2023
- Engelska 15 s.
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Ingår i: Nature Cardiovascular Research. - : Springer Science and Business Media LLC. - 2731-0590. ; 2:2, s. 144-158
- Relaterad länk:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Somatic mutations in blood indicative of clonal hematopoiesis of indeterminate potential (CHIP) are associated with an increased risk of hematologic malignancy, coronary artery disease and all-cause mortality. Here we analyze the relation between CHIP status and incident peripheral artery disease (PAD) and atherosclerosis, using whole-exome sequencing and clinical data from the UK Biobank and the Mass General Brigham Biobank. CHIP associated with incident PAD and atherosclerotic disease across multiple beds, with increased risk among individuals with CHIP driven by mutation in DNA damage repair (DDR) genes, such as TP53 and PPM1D. To model the effects of DDR-induced CHIP on atherosclerosis, we used a competitive bone marrow transplantation strategy and generated atherosclerosis-prone Ldlr −/− chimeric mice carrying 20% p53-deficient hematopoietic cells. The chimeric mice were analyzed 13 weeks after grafting and showed increased aortic plaque size and accumulation of macrophages within the plaque, driven by increased proliferation of p53-deficient plaque macrophages. In summary, our findings highlight the role of CHIP as a broad driver of atherosclerosis across the entire arterial system beyond the coronary arteries and provide genetic and experimental support for a direct causal contribution of TP53-mutant CHIP to atherosclerosis.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
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- art (ämneskategori)
- ref (ämneskategori)
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Zekavat, Seyedeh ...
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Viana-Huete, Van ...
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Matesanz, Nuria
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Jorshery, Saman ...
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Zuriaga, María A ...
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Uddin, Md Mesbah
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visa fler...
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Trinder, Mark
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Paruchuri, Kaavy ...
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Zorita, Virginia
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Ferrer-Pérez, Al ...
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Amorós-Pérez, Ma ...
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Kunderfranco, Pa ...
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Carriero, Robert ...
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Greco, Carolina ...
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Aroca-Crevillen, ...
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Hidalgo, Andrés
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Damrauer, Scott ...
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Ballantyne, Chri ...
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Niroula, Abhishe ...
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Gibson, Christop ...
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Pirruccello, Jam ...
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Griffin, Gabriel
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Ebert, Benjamin ...
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Libby, Peter
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Fuster, Valentín
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Zhao, Hongyu
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Ghassemi, Marzye ...
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Natarajan, Prade ...
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Bick, Alexander ...
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Fuster, José J.
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Klarin, Derek
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Kardiologi
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Nature Cardiovas ...
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Lunds universitet