FOXOs in the impaired heart: New therapeutic targets for cardiac diseases

Area of Science:

• Cardiology
• Molecular Biology
• Genetics

Background:

• Cardiac diseases present a significant global health burden.
• Accumulating evidence highlights the critical involvement of Forkhead box O (FOXO) transcription factors in cardiac pathophysiology.
• A comprehensive understanding of FOXOs' molecular mechanisms in the heart is needed.

Purpose of the Study:

• To review the molecular features, regulation, and cardiac actions of FOXO pathways.
• To elucidate the roles of FOXOs in major cardiac diseases, including ischemic heart disease, diabetic cardiomyopathy, and myocardial hypertrophy.
• To discuss methodological challenges in FOXO gene-modified animal models and suggest future research directions.

Main Methods:

• Literature review of current research on FOXOs in cardiovascular science.
• Analysis of molecular mechanisms and regulatory networks involving FOXOs in cardiac cells.
• Examination of data from gene-modified animal models relevant to cardiac diseases.

Main Results:

• FOXO proteins are key regulators of cellular processes in the heart, influencing stress response, metabolism, and survival.
• Dysregulation of FOXO signaling is implicated in the progression of various cardiac pathologies.
• Methodological limitations in current animal models may affect the interpretation of FOXO functions.

Conclusions:

• FOXO transcription factors are pivotal in maintaining cardiac homeostasis and are implicated in disease development.
• Targeting FOXO pathways holds therapeutic potential for managing cardiac diseases.
• Further research, particularly addressing model system limitations, is warranted to fully harness FOXOs for clinical applications.