Hearts, Volume 4, Issue 4 (December 2023) – 5 articles

Cardiomyopathies are major causes of heart failure. Chagas disease (CD) is caused by the parasite Trypanosoma cruzi, and it is endemic in Central and South America. Thirty percent of cases evolve into chronic chagas cardiomyopathy (CCC), which has worse prognosis as compared with other cardiomyopathies. In vivo bioenergetic analysis and ex vivo proteomic analysis of myocardial tissues highlighted worse mitochondrial dysfunction in CCC, and previous studies identified nuclear-encoded mitochondrial gene variants segregating with CCC. Here, we assessed the role of the mitochondrial genome through mtDNA copy number variations and mtDNA haplotyping and sequencing from heart or blood tissues of severe, moderate CCC and asymptomatic/indeterminate Chagas disease as well as healthy controls as an attempt to help decipher mitochondrial-intrinsic genetic involvement in Chagas disease development. We have found that the mtDNA copy number was significantly lower in CCC than in heart tissue from healthy individuals, while blood mtDNA content was similar among asymptomatic Chagas disease, moderate, and severe CCC patients. An MtDNA haplogrouping study has indicated that African haplogroups were over represented in the Chagas subject groups in comparison with healthy Brazilian individuals. The European lineage is associated with protection against cardiomyopathy and the macro haplogroup H is associated with increased risk towards CCC. Using mitochondria DNA sequencing, 84 mtDNA-encoded protein sequence pathogenic variants were associated with CCC. Among them, two variants were associated to left ventricular non-compaction and two to hypertrophic cardiomyopathy. The finding that mitochondrial protein-coding SNPs and mitochondrial haplogroups associate with risk of evolving to CCC is consistent with a key role of mitochondrial DNA in the development of chronic chagas disease cardiomyopathy. Full article

The epicardium is a very dynamic cardiac layer with pivotal contributions during cardiogenesis, acting in the postnatal period as an apparently dormant single-cell layer. In mammalian embryos, the epicardium, which originates form the proepicardium, translocates into the pericardial cavity and subsequently rests on the surface of the myocardium. Later, it gives rise to the epicardium-derived cells, which migrate into subepicardial space, invade the developing myocardium, promoting its growth, and contribute to different cell types. Anomalies in the process of epicardial development, the generation of epicardium-derived cells and their signaling mechanisms in different experimental models lead to defective cardiac development, reminiscent of human congenital heart diseases. Furthermore, recent studies have reported that epicardial derivates in adults, i.e., epicardial adipose tissue, are associated with electrophysiological cardiovascular anomalies. Herein, we provide a state-of-the-art review focusing on both congenital and adult heart diseases associated with epicardial development. Full article