Why the study?
The mechanisms linking post-MI cardiac insufficiency to skeletal muscle atrophy and the molecular basis for exercise's beneficial effects remained unclear.
Does aerobic exercise prevent IL-27-induced muscle atrophy in post-myocardial infarction cardiac insufficiency?
Does aerobic exercise prevent IL-27-induced muscle atrophy in post-myocardial infarction cardiac insufficiency?
Exercise mitigates post-MI skeletal muscle atrophy by suppressing HIF-1α-dependent IL-27 secretion and promoting M2-like macrophage polarization.
Should not yet change post-MI rehabilitation; leaves open human confirmation of exercise against muscle atrophy.
BACKGROUND: Skeletal muscle atrophy is a common complication of heart failure, with myocardial infarction (MI) being the primary cause. Yet, the mechanisms linking post-MI cardiac insufficiency to muscle atrophy have remained unclear. The molecular basis for the beneficial effects of exercise on exercise intolerance in MI patients also remains absent. METHODS: Serum IL-27 levels were measured in 48 MI patients and correlated with cardiac injury markers. Along with this, a rat model of post-MI cardiac insufficiency was used to assess skeletal muscle mass, cross-sectional area (CSA) of muscle fibers, and the expression of atrophy-related (MAFbx, MuRF-1) and differentiation-related markers (MyoD, Myogenin). The impact of exercise on muscle atrophy, cardiac inflammation, and IL-27 expression was then evaluated, with a focus on macrophage polarization. In vitro, the effects of macrophage-derived IL-27 on L6 myotube metabolism were assessed, and the role of HIF-1α in macrophage-derived IL-27 secretion was examined using co-culture systems. RESULTS: Serum IL-27 level was significantly elevated in MI patients and that it was positively correlated with myocardial injury and cardiac insufficiency. In post-MI rats, skeletal muscle mass and CSA of muscle fibers were reduced. Meanwhile, the expression level of myogenic markers was downregulated, while that atrophy markers was upregulated. IL-27 treatment promoted catabolism in L6 myotubes, and of note, HIF-1α overexpression in macrophages enhanced IL-27 secretion, and increased MAFbx and MuRF-1 expression. IL-27 level was also elevated in the heart, serum, and gastrocnemius muscle of MI rats. Exercise counteracted these effects by promoting M2-like macrophage polarization and suppressing HIF-1α, thereby reducing IL-27 expression. Furthermore, exercise ameliorated IL-27-induced muscle atrophy via the WSX-1/gp130/pSTAT3 signaling axis. CONCLUSION: IL-27 contributes to muscle atrophy in post-MI cardiac insufficiency. Exercise attenuates IL-27-driven muscle wasting by modulating inflammation and promoting M2-like macrophage polarization. These findings provide insights into the mechanisms of MI-induced muscle atrophy and highlight the therapeutic potential of exercise in cardiac rehabilitation.
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Li et al. (2026) studied this question.
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