Ubiquitin, p62, and Microtubule-Associated Protein 1 Light Chain 3 in Cardiomyopathy.

Abstract

Background: The accumulation of ubiquitinated proteins has been detected in diseased hearts and has been associated with the expression of p62 and microtubule-associated protein 1 light chain 3 (LC3), which are related to autophagy. We evaluated differences in ubiquitin accumulation and p62 and LC3 expression in cardiomyopathy using endomyocardial biopsies. Methods and Results: We studied 24 patients (aged 24-70 years; mean age 55 years) diagnosed with dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), or non-cardiomyopathy (NCM) who underwent endomyocardial biopsy. Biopsied samples were evaluated by microscopy for ubiquitin accumulation and expression of p62 and LC3. Ubiquitin accumulation and p62 and LC3 expression were observed in all patients. Ubiquitin accumulation was higher in DCM than in HCM or NCM; p62 expression was higher in DCM than in HCM. There were no significant differences in LC3 expression among the groups. Ubiquitin accumulation was significantly related to serum N-terminal pro B-type natriuretic peptide concentration and the expression of p62, but not LC3. Conclusions: Ubiquitin accumulation was more prominent in DCM than in HCM and NCM, which may be due to a relative shortage of clearance, including autophagy, compared with production.