Division of Cardiac Surgery Intensive Care Unit, Department of Cardiac Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
National Key Laboratory for Innovation and Transformation of Luobing Theory. Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.
Commun Biol. 2024 Nov 29;7(1):1594. doi: 10.1038/s42003-024-07304-0.
Insulin-like growth factor-binding protein 5 (IGFBP5) has been shown to be useful for the diagnosis and treatment of multiple tumors and cerebrovascular diseases. However, it is unknown whether IGFBP5 is involved in myocardial repair following myocardial infarction (MI). Here we show high expression of IGFBP5 in multiple models of ischemic and hypoxic injury. IGFBP5 affected the proliferation of neonatal rat cardiomyocytes (NRCMs) and the cardiomyocyte apoptosis induced by oxygen-glucose deprivation (OGD). Subsequently, heart-specific IGFBP5 knockdown inhibited myocardial apoptosis and increased cardiomyocyte proliferation in mice with MI. During the chronic remodeling stage, heart-specific regulation of IGFBP5 ameliorated pathological cardiac remodeling and dysfunction. Mechanistically, IGFBP5 regulated cardiomyocyte survival through the insulin-like growth factor 1 (IGF1) receptor (IGF1R)/protein kinase B (PKB/AKT) pathway. In summary, our results provide mechanistic insights into the effect of IGFBP5 on cardiomyocyte during cardiac repair. IGFBP5 may represent a therapeutic target for myocardial ischemic injury.
胰岛素样生长因子结合蛋白 5（IGFBP5）已被证明可用于多种肿瘤和脑血管疾病的诊断和治疗。然而，IGFBP5 是否参与心肌梗死后的心肌修复尚不清楚。在这里，我们在多种缺血和缺氧损伤模型中显示 IGFBP5 的高表达。IGFBP5 影响新生大鼠心肌细胞（NRCMs）的增殖和氧葡萄糖剥夺（OGD）诱导的心肌细胞凋亡。随后，心肌特异性 IGFBP5 敲低抑制了 MI 小鼠的心肌细胞凋亡并增加了心肌细胞增殖。在慢性重塑阶段，心肌特异性调节 IGFBP5 改善了病理性心脏重塑和功能障碍。从机制上讲，IGFBP5 通过胰岛素样生长因子 1（IGF1）受体（IGF1R）/蛋白激酶 B（PKB/AKT）途径调节心肌细胞的存活。总之，我们的研究结果为 IGFBP5 在心脏修复过程中对心肌细胞的作用提供了机制上的见解。IGFBP5 可能代表心肌缺血损伤的治疗靶点。
