Mitochondrial Collapse Responsible for Chagasic and Post Is-chemic Heart Failure Is Reversed by Cell Therapy Under Different Transcriptomic Topology

Gene expression data from our publicly accessible transcriptomic dataset obtained by profiling the left ventricle myocardia of mouse models of Chagasic cardiomyopathy and post-ischemic heart failure were re-analyzed from the perspective of the Genomic Fabric Paradigm. In addition to the regulation of the gene expression levels, we determined the changes in the strength of the homeostatic control of transcript abundance and the remodeling of the gene networks responsible for the mitochondrial respiration. The analysis revealed that most of the mitochondrial genes assigned to the five complexes of the respiratory chain were significantly down-regulated by both Chagas disease and ischemia but exhibit outstanding recovery of the normal expression levels following direct injection of bone marrow-derived stem cells. However, instead of regaining the original expression control and gene networking, the treatment induced novel mitochondrial arrangements, suggesting that multiple transcriptomic topologies might be compatible with any given physiological or pathological state. The study confirmed several established mechanisms, and introduce new signals, especially Cox4i2, Cox6b1, Cox7b, Ndufb11, and Tmem186, that warrant further investigations. Their broad rescue with cell therapy underscores mitochondria as a convergent, tractable target for cardiac repair.