The cytoskeleton of the myocardium served as the foundation for organelle function, bioenergetics, and cardiac remodeling. The weakening of the myocardial cytoskeleton in the failing heart of individuals with severe chronic renal disease has largely gone unnoticed to date. Explanted human heart tissues from hemodialysis patients (n=19), hypertension patients (n=10) with maintained renal function, and healthy controls (n=21) were researched in 3-arm cross-sectional cohort research. Pathologic investigation and next-generation RNA sequencing were performed on left ventricular samples. In vitro human cardiac fibroblast cultures were conducted mechanistic and interference RNA experiments.

In comparison with hypertension patients (P<0.05) and controls (P<0.01), left ventricular tissues from hemodialysis patients had increased myocardial wall thickness and significantly more fibrosis. According to transcriptomic analysis, the focal adhesion pathway was considerably enriched in hearts from hemodialysis patients. When compared with controls, hearts from hemodialysis patients had dysregulated components of the focal adhesion pathway, including reduced Beta-actin (P<0.01), Beta-tubulin (P<0.01), vimentin (P<0.05), and increased expression of vinculin (P<0.05). The hemodialysis group’s cytoskeletal modifications were linked to defective mitochondrial bioenergetics, including dysregulated mitochondrial dynamics and fusion and the loss of cell survival pathways. According to mechanistic investigations, in vitro, uremic and metabolic anomalies of chronic kidney illness could have promoted cytoskeletal alterations. Furthermore, interference RNA-mediated silencing of focal adhesion kinase synergistically decreased essential cytoskeletal proteins with mineral stresses observed in chronic kidney disease in vitro. In late chronic renal disease, myocardial failure was characterized by cytoskeleton dysfunction, including disruption of the focal adhesion route, mitochondrial failure, and loss of cell survival pathways.

Source –www.ahajournals.org/doi/10.1161/JAHA.121.022991