作者
Yoshimitsu Yura, Emiri Miura-Yura, Yasufumi Katanasaka, Kyung-Duk Min, Nicholas Chavkin, Ariel H Polizio, Hayato Ogawa, Keita Horitani, Heather Doviak, Megan A Evans, Miho Sano, Ying Wang, Katharina Boroviak, George Philippos, Ana Filipa Domingues, George Vassiliou, Soichi Sano, Kenneth Walsh
发表日期
2021/9/3
期刊
Circulation research
卷号
129
期号
6
页码范围
684-698
出版商
Lippincott Williams & Wilkins
简介
Rationale
Cancer therapy can be associated with short- and long-term cardiac dysfunction. Patients with cancer often exhibit therapy-related clonal hematopoiesis (t-CH), an aggressive form of clonal hematopoiesis that can result from somatic mutations in genes encoding regulators of the DNA-damage response (DDR) pathway. Gain-of-function mutations in exon 6 of the protein phosphatase Mg2+/Mn2+ dependent 1D (PPM1D) gene are the most frequently mutated DNA-damage response gene associated with t-CH. Whether t-CH can contribute to cardiac dysfunction is unknown.
Objective
We evaluated the causal and mechanistic relationships between Ppm1d-mediated t-CH and nonischemic heart failure in an experimental system.
Methods and Results
To test whether gain-of-function hematopoietic cell mutations in Ppm1d can increase susceptibility to cardiac stress, we evaluated cardiac dysfunction in a …
学术搜索中的文章
Y Yura, E Miura-Yura, Y Katanasaka, KD Min… - Circulation research, 2021