Nuclear hypertrophy reflects increased biosynthetic activities in myocytes of human hypertrophic hearts

Area of Science:

• Cardiovascular Biology
• Cellular and Molecular Medicine
• Cardiac Pathophysiology

Background:

• Human hypertrophic hearts exhibit myocyte nuclear abnormalities, including bizarre shapes and chromatin clumping.
• The functional implications of these nuclear alterations in heart disease remain largely undetermined.

Purpose of the Study:

• To investigate the relationship between nuclear structural changes and molecular events in myocytes from various human hypertrophic heart conditions.
• To determine the functional significance of nuclear hypertrophy in the context of cardiac remodeling and failure.

Main Methods:

• Analysis of left ventricular endomyocardial biopsies from patients with dilated cardiomyopathy, postmyocarditis, hypertrophic cardiomyopathy, apical hypertrophic cardiomyopathy, hypertensive heart disease, and controls.
• Assessment of myocyte size, LV mass index, nuclear hypertrophy score, and biosynthetic activities (DNA repair/synthesis, transcription, translation) using immunohistochemistry.

Main Results:

• Nuclear hypertrophy scores were elevated in all hypertrophic hearts compared to controls, particularly in those with systolic failure (DCM, postmyocarditis).
• Increased biosynthetic activities, including DNA repair/synthesis (PCNA), transcription (spliceosome), and translation (S6 kinase), were observed and correlated with nuclear hypertrophy.
• Oxidative DNA damage markers were frequently co-expressed in PCNA-positive nuclei, indicating DNA repair activity.

Conclusions:

• Nuclear hypertrophy in myocytes of human hypertrophic hearts is linked to structural alterations and increased molecular biosynthetic activities.
• These findings suggest that nuclear hypertrophy reflects heightened DNA repair/synthesis, transcription, and translation efficiency in response to cardiac stress.