The Cancer Therapy-Related Clonal Hematopoiesis Driver Gene Ppm1d Promotes Inflammation and Non-Ischemic Heart Failure in Mice

Circ Res. 2021 Sep 3;129(6):684-698. doi: 10.1161/CIRCRESAHA.121.319314. Epub 2021 Jul 28.

Yoshimitsu Yura¹, Emiri Miura-Yura¹, Yasufumi Katanasaka², Kyung-Duk Min¹, Nicholas Chavkin¹, Ariel H Polizio¹, Hayato Ogawa¹, Keita Horitani¹, Heather Doviak¹, Megan A Evans¹, Miho Sano¹, Ying Wang^{1

3}, Katharina Boroviak⁴, George Philippos^{4

5}, Ana Filipa Domingues^{4

6}, George Vassiliou^{4

6}, Soichi Sano^{1

7}, Kenneth Walsh

¹ Hematovascular Biology Center, Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA (Y.Y., E.M.-Y., K.-D.M., N.C., A.H.P., H.O., K.H., H.D., M.A.E., M.S., Y.W., S.S., K.W.).
² Now with Division of Molecular Medicine, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Yada, Japan (Y.K.).
³ Department of Cardiology, Xinqiao Hospital, Army Medical University, Chongqing, China (Y.W.).
⁴ Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, United Kingdom (K.B., G.P., G.V., A.F.D.).
⁵ Now with Interfaculty Institute of Cell Biology, Eberhard Karls University Tübingen, Germany (G.P.).
⁶ Wellcome-MRC Cambridge Stem Cell Institute, Department of Haematology, University of Cambridge, United Kingdom (A.F.D., G.V.).
⁷ Now with Department of Cardiology, Osaka City University Graduate School of Medicine, Japan (S.S.).

Abstract

[Figure: see text].

Keywords: CRISPR-Cas Systems; DNA damage; cardiotoxicity; clonal hematopoiesis; heart failure; inflammasome; macrophages.