Clues to the Onset of Hypertrophic Cardiomyopathy Found in Fish Model

Korea National Institute of Health Identifies Mechanisms Using Zebrafish Model
Cardiac Hypertrophy Observed with ATF3 Overexpression

A new study has identified the causal mechanisms of hypertrophic cardiomyopathy, a condition in which the heart muscle becomes abnormally thick, using a fish model.

On March 11, the Korea National Institute of Health announced that it had confirmed in a zebrafish animal model that abnormal overexpression of ATF3, a transcription factor involved in the stress response, causes the heart to enlarge abnormally and disrupts the heart’s electrical signals, resulting in features similar to hypertrophic cardiomyopathy. The results of this study were published in the international journal 'Scientific Reports' (2026, Volume 16, Article 3143).

Cardiac hypertrophy and myocardial structural abnormalities observed in ATF3-overexpressing zebrafish. National Institute of Health Research

The Korea National Institute of Health is conducting research to identify genes responsible for hereditary cardiovascular diseases and to elucidate the process by which these diseases develop, using a zebrafish animal model. Zebrafish share about 70% genetic similarity with humans, and approximately 82% of disease-related genes are conserved, making them a useful model for studying diseases and genes.

In this study, the impact of ATF3 overexpression on cardiac hypertrophy and electrical function was investigated. When the researchers induced expression of the human ATF3 gene in the zebrafish heart, they observed cardiac hypertrophy, with heart size increasing approximately 2.5 to 3 times compared to normal and enlargement of myocardial cells. Cardiac tissue damage was also observed, including abnormalities in cardiac muscle fiber structure and increased fibrosis. The expression of cell death-related genes decreased, while the expression of proliferation-related genes increased. These results suggest that ATF3 overexpression may be associated with cardiac hypertrophy accompanied by abnormal proliferation of cardiac cells.

Kim Wonho, head of the Department of Chronic Disease Convergence Research at the Korea National Institute of Health and lead researcher of the study, stated, "This research is significant in that it is the first to elucidate the mechanisms of cardiac hypertrophy induced by ATF3 in zebrafish," adding, "We will continue to pursue research to identify the mechanisms of various chronic diseases and to discover therapeutic targets."

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