Clusterin, through exercise-mediated liver-heart crosstalk, promotes heart regeneration after myocardial infarction.

Exercise-induced exerkine clusterin promotes post–myocardial infarction heart regeneration in adult mice, with cardiac-specific Clu knockout reducing and clusterin overexpression enhancing recovery.

• Why it matters: Cardiomyocyte loss after MI drives remodeling and heart failure, and while exercise improves repair, the mechanism linking exercise signals to cardiac regeneration is unclear.
• What they did: The study used cardiac-specific Clu knockout and clusterin overexpression, tested recombinant clusterin after MI, and showed liver-derived clusterin via hepatocyte-specific Clu knockdown; mechanistically, clusterin activated NF-κB through proteasome-dependent IκBα degradation by binding IκBα.
• The result: Clusterin mediates the pro-regenerative effect of running plasma on cardiac repair and cardiomyocyte proliferation after MI, supporting liver-heart crosstalk as a therapeutic target for post-MI heart failure.

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