JACC. CardioOncology
Fibrotic Rewiring of CD8+ T Cells by Doxorubicin Drives Pathological Remodeling of Cardiac Extracellular Matrix
By Bayer AL, Emig R, Kley C and 8 others.
Abstract
Background
Anthracycline chemotherapy can lead to cardiotoxicity and chronic heart failure, and specific preventative therapies are nonexistent to date. As such, mechanistic investigation is needed to develop cardioprotective strategies. We previously showed that the anthracycline doxorubicin elicits a cardiotropic CD8+ T-cell response that contributes to cardiac fibroblast transformation, fibrosis, and chronic cardiotoxicity. However, the exact molecular mechanisms of T-cell-induced fibrosis, and whether T cells can directly induce cardiac remodeling, remain unknown.
Objectives
We sought to investigate T-cell transcriptomes from anthracycline-treated patients, mice, and cultured T cells to better understand mechanisms by which T cells influence adverse cardiac remodeling upon doxorubicin treatment across species.