Lack of genetic recovery despite phenotypic recovery - are these the key to understanding remission vs recovery from heart failure? - Genetic analysis of a mouse model of recovery

Heart failure (HF) remission involves the normalization of cardiac function but is accompanied by a risk of relapse. The key to achieving (complete) recovery may lie in identifying genes that remain persistently dysregulated despite phenotypic normalization. We used a mouse model of non-ischemic HF recovery to identify persistently dysregulated genes in phenotypically recovered myocardium compared to HF. RNA-seq data from male C57BL/6 mice that underwent HF induction followed by phenotypic recovery were analyzed. Differential expression analyses identified 18 persistently altered genes: 17 were upregulated, and 1 was downregulated. Notably, the only downregulated gene was the transferrin receptor gene (<i>Tfrc</i>), whereas transferrin (<i>Trf</i>) was upregulated, suggesting a role of ferroptosis pathways. Persistently dysregulated genes, especially those related to iron metabolism and ferroptosis, are potential therapeutic targets to sustain cardiac recovery from HF.