Core Findings - The study identifies a crucial subpopulation of injury-induced Clusterin⁺ (Clu⁺) cardiomyocytes that play a key regulatory role in cardiac regeneration in young mammals [3][5] - Clu⁺ cardiomyocytes reprogram macrophages to coordinate repair and anti-inflammatory activities, which is essential for heart regeneration [4][7] - The research reveals that the CLU-TLR4 signaling pathway reprograms macrophages into an anti-inflammatory and repair state, while the CLU-BMP2 signaling axis promotes cardiomyocyte proliferation and restores regenerative capacity in adult hearts [5][7] Mechanisms of Action - After cardiac injury, Clu⁺ cardiomyocytes appear in the marginal areas of the regenerating heart, while they are scarce in non-regenerative contexts [4] - Macrophages secrete CLU, which binds to TLR4 on macrophages, reducing inflammation and promoting repair through Cpt1a-dependent fatty acid oxidation [4] - The study finds that decreased CLU levels in patients with myocardial infarction correlate with impaired cardiac function, while overexpression of CLU or transplantation of engineered Clu⁺ human cardiac organoids enhances myocardial repair in adult mice [4][5] Implications for Future Research - This research provides a new theoretical and technical pathway for cardiac regeneration post-myocardial infarction, highlighting the potential for therapeutic strategies targeting the Clu⁺ cardiomyocyte and macrophage interaction [3][7]

Core Viewpoint - The study highlights the role of LYZ2 in mediating remote injury responses in the heart, suggesting that targeting LYZ2 in endocardial cells can promote rapid recovery of non-regenerative hearts after myocardial infarction [3][4][6]. Group 1: Research Findings - Local cardiac injury leads to significantly elevated expression of Lyz2 in both the damaged area and remote regions [7]. - Lyz2 acts as a positive regulator of lysosomal degradation triggered by remote injury [7]. - Gene knockout of Lyz2 can result in rapid functional recovery after myocardial infarction [7]. - Pharmacological inhibition of lysosomal degradation has cardioprotective effects [7]. Group 2: Implications for Treatment - The findings suggest that targeting remote injury responses in non-myocyte cell types could facilitate swift recovery of non-regenerative hearts post-myocardial infarction [6][7].