The altered expression of autophagy-related genes participates in heart failure: NRBP2 and CALCOCO2 are associated with left ventricular dysfunction parameters in human dilated cardiomyopathy.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Adaptor Proteins, Signal Transducing/*genetics ; Autophagy-Related Proteins/*genetics ; Cardiomyopathy, Dilated/*genetics ; Nuclear Proteins/*genetics ; RNA, Messenger/*genetics ; Receptors, Cytoplasmic and Nuclear/*genetics ; Ventricular Dysfunction, Left/*genetics; Adaptor Proteins, Signal Transducing/metabolism ; Adrenergic beta-Antagonists/therapeutic use ; Adult ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Autophagy/genetics ; Autophagy-Related Proteins/metabolism ; Cardiomyopathy, Dilated/drug therapy ; Cardiomyopathy, Dilated/metabolism ; Cardiomyopathy, Dilated/physiopathology ; Case-Control Studies ; Diuretics/therapeutic use ; Female ; Gene Expression Profiling ; Gene Expression Regulation ; Heart Ventricles/metabolism ; Heart Ventricles/pathology ; Humans ; Male ; Middle Aged ; Mineralocorticoid Receptor Antagonists/therapeutic use ; Myocardium/metabolism ; Myocardium/pathology ; Nuclear Proteins/metabolism ; RNA, Messenger/metabolism ; Receptors, Cytoplasmic and Nuclear/metabolism ; Sequence Analysis, RNA ; Ventricular Dysfunction, Left/drug therapy ; Ventricular Dysfunction, Left/metabolism ; Ventricular Dysfunction, Left/physiopathology

This study aimed to analyze changes in the expression of autophagy- and phagocytosis-related genes in patients with dilated cardiomyopathy (DCM), especially in relation to left ventricular (LV) dysfunction. Furthermore, transmission electron microscopy of the diseased tissue was carried out to investigate if the gene expression changes are translated into ultrastructural alterations. LV tissue samples from patients with DCM (n = 13) and from controls (CNT; n = 10) were analyzed by RNA-sequencing, whereupon 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. 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.
Competing Interests: The authors have declared that no competing interests exist.

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0 (Adaptor Proteins, Signal Transducing)
0 (Adrenergic beta-Antagonists)
0 (Angiotensin-Converting Enzyme Inhibitors)
0 (Autophagy-Related Proteins)
0 (CALCOCO2 protein, human)
0 (Diuretics)
0 (Mineralocorticoid Receptor Antagonists)
0 (NRBP2 protein, human)
0 (Nuclear Proteins)
0 (RNA, Messenger)
0 (Receptors, Cytoplasmic and Nuclear)

Date Created: 20190423 Date Completed: 20200113 Latest Revision: 20200309

20240829

PMC6476534

10.1371/journal.pone.0215818

31009519