Purpose: This study aimed to analyze changes in the expression of autophagy- and phagocytosis-related genes in patients with DCM, especially in relation to left ventricular (LV) dysfunction. Furthermore, we investigated if the gene expression changes were translated into ultrastructural alterations.
Methods: Twenty-three human left ventricle tissue samples were obtained from DCM (n = 13) patients undergoing heart transplantation and control (CNT; n = 10) donors. Diagnosis of DCM was based on clinical history, Doppler echocardiography, and coronary angiography data. Total mRNA levels of heart samples were analyzed by RNA sequencing. Furthermore, transmission electron microscopy of the diseased tissue was carried out by a JEOL TEM system.
Results: The altered expression (P < 0.05) of 13 autophagy- and 3 phagocytosis-related genes was observed. The expression changes of the autophagy-related genes NRBP2 and CALCOCO2 were associated with cardiac dysfunction and remodeling (P < 0.05). The affected patients had a higher activity of these degradation processes, as evidenced by the greater number of autophagic structures in the DCM tissue (P < 0.001). Differences in the ultrastructural distribution were also found between the DCM and CNT tissues.
Conclusions: These results show that in patients with DCM, the altered expression of NRBP2 and CALCOCO2 is related to LV dysfunction and remodeling. Clarification of the molecular mechanisms of cardiac autophagy would help in the future development of therapies to improve LV performance.