Reduced myocardial CARF and the underlying implications in left ventricular noncompaction cardiomyopathy.

Abstract

Background: Left ventricular noncompaction cardiomyopathy (LVNC) has been used to describe a ventricular phenotype characterized by thick LV trabeculae and the formation of crypts by depression. Some studies have shown that apoptosis of cardiomyocytes leads to impaired development and densification, resulting in LVNC formation. The applicant's previous results showed that CARF protein was specifically down-regulated in myocardial tissue of LVNC disease, and the pathway specifically enriched in LVNC was the p53 apoptosis pathway, and CARF was enriched in the p53 apoptosis pathway.

Methods: Comparative proteomic analysis by iTRAQ-2DLC-MS/MS was used to screen differentially expressed proteins in heart samples obtained from heart transplantation patients diagnosed with LVNC, ARVC, and HCM in comparison to normal heart samples. Decresing expressed CARF in heart samples from LVNC was further confirmed by Western blot. Immunofluorescence, western blots were used to study the effects of knock out CARF on the structure and function of HL1 cardiomyocytes. Functional and morphological changes were observed by TUNEL staining in cardiomyocytes whose left ventricle knock out CARF.

Results: In our study, CARF protein is specifically down-regulated in myocardial tissue of LVNC disease. The pathway specifically enriched in LVNC is the p53 apoptosis pathway, and CARF is enriched in the p53 apoptosis pathway. We hypothesized that CARF interacts with p53 to influence apoptotic pathway activity resulting in LVNC. In view of the localization and function of CARF in the heart, we hypothesized that knock out the CARF might be involved in the apoptosis pathway and participated in the molecular mechanism of LVNC.

Conclusion: Myocardial CARF phosphorylation participate in the apoptosis pathway which result in cardiomyocytes apoptosis. Our findings suggest that decreased myocardial CARF might be involved in the molecular mechanism of LVNC. CARF participates in the occurrence and development of LVNC by mediating the p53 pathway, so as to develop new therapeutic targets for LVNC.