Heart failure is a common disease with poor prognosis that is associated with cardiac immune cell infiltration and dysregulated cytokine expression. Recently, the clonal expansion of hematopoietic cells with acquired (i.e., nonheritable) DNA mutations, a process referred to as clonal hematopoiesis, has been reported to be associated with cardiovascular diseases including heart failure. Mechanistic studies have shown that leukocytes that harbor these somatic mutations display altered inflammatory characteristics that worsen the phenotypes associated with heart failure in experimental models. In this review, we summarize recent epidemiological and experimental evidence that support the hypothesis that clonal hematopoiesis-mediated immune cell dysfunction contributes to heart failure and cardiovascular disease in general.
Keywords: ASXL1, additional sex combs like 1; DNMT3A; DNMT3A, DNA methyltransferase-3A; HSPCs, hematopoietic stem and progenitor cells; IL, interleukin; Il-1β inflammasome; JAK2; JAK2, janus kinase 2; MPN, myeloproliferative neoplasm; PPM1D, protein phosphatase, Mg2+/Mn2+ dependent 1D; TET2; TET2, ten-eleven translocation-2; TNF, tumor necrosis factor; TNF-α; TP53, tumor protein 53; VAF, variant allele fraction; hsCRP, high-sensitivity C-reactive protein.
© 2020 The Authors.