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Master Thesis

Rôle de l'hématopoïèse clonale de potentiel indéterminé dans les évènements cardiovasculaires : impact sur l’inflammation et l’athérosclérose

Abstract : Clonal hematopoiesis of indeterminate potential (CHIP) defines the acquisition of somatic mutations in leukemia-driver genes in hematopoietic cells without any hematological malignancy. This condition has been associated with atherothrombosis and cardiovascular complications via the induction of a chronic inflammatory state in mice. The purpose of this study was to evaluate in human the impact of the presence of a CHIP on inflammation and atherosclerosis in a population of patients aged of at least 75 years and suffering from a first myocardial infarction. The study cohort comprised 106 patients having a first myocardial infarction from atherosclerosis origin (age 82 [79-87] years). Between two and seven months after the acute event, CHIP were searched by Next Generation Sequencing of 56 genes. At this time, supra-aortic trunks ultrasonography with 3D-measurement of atherosclerotic volume and high sensitive CRP (hsCRP) dosage were performed. CHIP mutations with a variant allelic frequency ≥2% were detected in 55% of patients and were associated with a significant increase of hsCRP plasmatic levels (2.7 mg/L vs 1.2 mg/L, p=0.0127). However, we did not observed any difference in atherosclerosis burden between CHIP carriers and no-carriers. These results are also observed when restricting analysis on the mutations affecting the two main genes, DNA methyltransferase 3 alpha (DNMT3A) and Ten eleven translocation 2 (TET2). Interestingly, CHIP carriers presented a 3-fold higher risk of recurrence of cardiovascular event between the first event and the inclusion in the study. In conclusion, CHIP is common among patients suffering a first myocardial infarction after 75 years and is associated with a higher chronic inflammatory state, with a possible effect of clone size and number of mutations detected in a same patient.
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Master Thesis
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https://dumas.ccsd.cnrs.fr/dumas-03436574
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Submitted on : Friday, November 19, 2021 - 2:10:35 PM
Last modification on : Friday, December 17, 2021 - 3:47:07 AM
Long-term archiving on: : Sunday, February 20, 2022 - 7:03:24 PM

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  • HAL Id : dumas-03436574, version 1

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Séverine Marti. Rôle de l'hématopoïèse clonale de potentiel indéterminé dans les évènements cardiovasculaires : impact sur l’inflammation et l’athérosclérose. Sciences du Vivant [q-bio]. 2021. ⟨dumas-03436574⟩

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