Key result
Clusterin promotes post-MI cardiac regeneration and cardiomyocyte proliferation via NF-κB activation in mice.
Why the study?
Loss of cardiomyocytes drives cardiac remodeling and heart failure, creating a need to promote cardiac regeneration. Although exercise enhances cardiac repair and stimulates cardiomyocyte proliferation, the underlying mechanisms remained unclear.
Does exercise-induced or recombinant clusterin promote cardiac regeneration and cardiomyocyte proliferation after myocardial infarction in mice?
Does exercise-induced or recombinant clusterin promote cardiac regeneration and cardiomyocyte proliferation after myocardial infarction in mice?
Identifies liver-derived clusterin as a key mediator of exercise-induced cardiac regeneration post-MI via NF-κB signaling, highlighting a potential therapeutic target for post-MI heart failure.
Suggests clusterin as a target to mimic exercise benefits after MI; leaves open whether it improves outcomes in patients.
Loss of cardiomyocytes drives cardiac remodeling and ultimately leads to heart failure, highlighting the need to promote cardiac regeneration. Exercise has been known to enhance cardiac repair and stimulate cardiomyocyte proliferation; however, the underlying mechanisms remain unclear. In this study, we demonstrated that exercise-induced exerkine clusterin mediates the pro-regenerative effects of running plasma on cardiac repair and cardiomyocyte proliferation following myocardial infarction (MI). Cardiac-specific Clu knockout attenuated, whereas clusterin overexpression enhanced, post-MI cardiac regeneration. Recombinant clusterin administration promoted heart regeneration in adult mice after MI. Mechanistically, clusterin activated NF-κB via proteasome-dependent IκBα degradation through direct binding with IκBα. Furthermore, the liver was identified as the major source of exercise-induced circulating clusterin; hepatocyte-specific Clu knockdown abolished the stimulatory effect of exercise plasma on cardiac regeneration. This study reveals a liver-heart crosstalk mechanism by which exercise-induced clusterin promotes cardiomyocyte proliferation, positioning clusterin as a potential therapeutic target for post-MI heart failure.
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Wang et al. (2026) studied Post-myocardial infarction cardiac regeneration. Exercise-induced or recombinant clusterin (and Clu overexpression/knockout) vs. Control / Clu knockout or knockdown was evaluated on Post-myocardial infarction cardiac regeneration and cardiomyocyte proliferation. Exercise-induced liver-derived clusterin and recombinant clusterin administration promoted post-MI heart regeneration and cardiomyocyte proliferation via NF-κB activation in mice.
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