Leucine-rich repeat neuronal protein 4 (LRRN4) potentially functions in dilated cardiomyopathy

Leucine-rich repeat neuronal protein-4 (LRRN4 or NLRR4) has been identified as a new member of LRRN family, which is a group of proteins that contain leucine-rich repeat domains and functioned as regulators in a variety of pathologic processes including cardiac remodeling. However, the exact pattern of expression and function of LRRN4 in the human hearts is still unclear. In our study, the western blot test and real-time PCR were performed to detect the LRRN4 level in hearts of patients with dilated cardiomyopathy (DCM), ischemia heart disease (IHD) hearts respectively. Interestingly, the LRRN4 was highly expressed in donor hearts, but significantly reduced in hearts with DCM. While a comparable level of expression was detected in the IHD hearts when compared with donor hearts. Immunohistochemistry assay showed that LRRN4 was particularly expressed in cardiomyocytes and responsible for its decreased expression in the DCM hearts. Furthermore, we found LRRN4 was expressed in the ventricular cardiomyocytes of mice and apparently reduced after pressure overload treatment in the wild type mice. Therefore, our hitherto unrecognized findings provided the first evidence that the highly expressed LRRN4 is critical for maintaining morphology and function of heart. In addition to that, since its expression level decreased in DCM hearts but not IHD hearts, which indicated LRRN4 might be a therapeutic target clinically for DCM disease.