Significance of low desmin expression in cardiomyocytes in patients with idiopathic dilated cardiomyopathy

Abstract

Desmin plays an essential role in maintaining cell cytoarchitecture, positioning and functioning of organelles, and the intercellular signaling pathway. It has been suggested that remodeling of desmin cytoskeleton might contribute to the progression of idiopathic dilated cardiomyopathy and might affect patients' long-term prognosis. We performed endomyocardial biopsy in 200 patients with idiopathic dilated cardiomyopathy. A total of 5 to 6 specimens were collected from the left ventricular (LV) wall. Desmin was detected with immunohistochemical staining and Western blotting. Immunohistochemistry revealed 4 types of desmin expression: I, normal staining at Z-lines and intercalated disks, giving a regular cross-section pattern; IIA, increased desmin staining at Z-lines and intercalated disks; IIB, increased desmin staining with irregular pattern of cross-striation and/or with presence of aggregates; and III, decreased or lack of desmin staining. Patients with type III had a greater New York Heart Association class and N-terminal pro-brain natriuretic peptide level, larger LV end-diastolic diameter, and lower LV ejection fraction than patients with type I (p <0.001). At the end of follow-up (mean duration 59 ± 33 months), 44 patients (22%) had died and 5 (2.5%) had undergone heart transplantation. Patients with type III had an increased risk of death or heart transplantation in univariate Cox proportional hazard regression models (adjusted hazard ratio 7.18, 95% confidence interval 2.96 to 17.40, p <0.001) and multivariate models (New York Heart Association class, LV end-diastolic diameter, LV ejection fraction, N-terminal pro-brain natriuretic peptide, gender, and age; hazard ratio 5.24, 95% confidence interval 1.58 to 17.38, p = 0.007). In conclusion, in patients with idiopathic dilated cardiomyopathy, a decrease or lack of desmin expression seems to be a strong, independent predictor of an unfavorable prognosis. Our outcomes support the relevance of exploring desmin expression as a potential target to treat heart failure progression.