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. 2023 Jul 6;5(8):323-330.
doi: 10.1253/circrep.CR-23-0058. eCollection 2023 Aug 10.

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

Ryo Eto  1 , Hiroaki Kawano  1 , Mutsumi Matsuyama-Matsuu  2 , Katsuya Matsuda  2 , Nozomi Ueki  2 , Masahiro Nakashima  2 , Shinji Okano  3 , Mitsuaki Ishijima  1 , Miho Kawakatsu  1 , Jumpei Watanabe  1 , Tsuyoshi Yoshimuta  1 , Satoshi Ikeda  1 , Koji Maemura  1
Affiliations

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

Ryo Eto et al. Circ Rep. .

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.

Keywords: Autophagy; Cardiomyopathy; Heart failure; Pathology.

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Conflict of interest statement

K.M. is a member of Circulation Reports’ Editorial Team. The remaining authors have no conflicts of interest to declare.

Figures

Figure 1.
Figure 1.
Microphotographs of biopsied myocardium in a patient with dilated cardiomyopathy. (A) Hematoxylin and eosin staining; (B) immunostaining for ubiquitin; (C) immunostaining for p62; and (D) immunostaining for microtubule-associated protein 1 light chain 3.
Figure 2.
Figure 2.
Microphotographs of biopsied myocardium in a patient with hypertrophic cardiomyopathy. (A) Hematoxylin and eosin staining; (B) immunostaining for ubiquitin; (C) immunostaining for p62; and (D) immunostaining for microtubule-associated protein 1 light chain 3.
Figure 3.
Figure 3.
Microphotographs of biopsied myocardium in a patient with hypertensive heart disease. (A) Hematoxylin and eosin staining; (B) immunostaining for ubiquitin; (C) immunostaining for p62; and (D) immunostaining for microtubule-associated protein 1 light chain 3.
Figure 4.
Figure 4.
(A) Ubiquitin, (B) p62, and (C) microtubule-associated protein 1 light chain 3 (LC3) expression in the biopsied myocardium of patients with dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), and non-cardiomyopathy (NCM).
Figure 5.
Figure 5.
Relationship between ubiquitin accumulation and the expression of p62 and microtubule-associated protein 1 light chain 3 (LC3) in the biopsied myocardium. There was a significant relationship between ubiquitin accumulation and p62, but not LC3, expression. There was no correlation between p62 expression and LC3 expression.
See this image and copyright information in PMC

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