TY  - JOUR
A1  - Shumliakivska, Mariana
A1  - Luxán, Guillermo
A1  - Hemmerling, Inga
A1  - Scheller, Marina
A1  - Li, Xue
A1  - Müller-Tidow, Carsten
A1  - Schuhmacher, Bianca
A1  - Sun, Zhengwu
A1  - Dendorfer, Andreas
A1  - Debes, Alisa
A1  - Glaser, Simone F.
A1  - Muhly-Reinholz, Marion
A1  - Kirschbaum, Klara
A1  - Hoffmann, Jedrzej
A1  - Nagel, Eike
A1  - Puntmann, Valentina O.
A1  - Cremer, Sebastian
A1  - Leuschner, Florian
A1  - Abplanalp, Wesley Tyler
A1  - John, David
A1  - Zeiher, Andreas M.
A1  - Dimmeler, Stefanie
T1  - DNMT3A clonal hematopoiesis-driver mutations induce cardiac fibrosis by paracrine activation of fibroblasts
T2  - Nature Communications
N2  - Hematopoietic mutations in epigenetic regulators like DNA methyltransferase 3 alpha (DNMT3A), play a pivotal role in driving clonal hematopoiesis of indeterminate potential (CHIP), and are associated with unfavorable outcomes in patients suffering from heart failure (HF). However, the precise interactions between CHIP-mutated cells and other cardiac cell types remain unknown. Here, we identify fibroblasts as potential partners in interactions with CHIP-mutated monocytes. We used combined transcriptomic data derived from peripheral blood mononuclear cells of HF patients, both with and without CHIP, and cardiac tissue. We demonstrate that inactivation of DNMT3A in macrophages intensifies interactions with cardiac fibroblasts and increases cardiac fibrosis. DNMT3A inactivation amplifies the release of heparin-binding epidermal growth factor-like growth factor, thereby facilitating activation of cardiac fibroblasts. These findings identify a potential pathway of DNMT3A CHIP-driver mutations to the initiation and progression of HF and may also provide a compelling basis for the development of innovative anti-fibrotic strategies.
Y1  - 2024
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/85553
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-855530
SN  - 2041-1723
VL  - 15
IS  - Article number 606
PB  - Nature Publishing Group UK
CY  - London
ER  -