Shen Hua, Wang Qing, Liu Bohan, Wang Yihui, Zhou Dandan, Zhang Lin, Zhuang Jinqiang
Department of Cardiovascular Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing, China.
Department of Adult Cardiac Surgery, The Sixth Medical Center of PLA General Hospital, Beijing, China.
Front Pharmacol. 2024 Oct 3;15:1463465. doi: 10.3389/fphar.2024.1463465. eCollection 2024.
Myocardial infarction (MI), a leading cause of heart failure, is characterized by the loss of cardiomyocytes, which severely limits the heart's regenerative capacity. The Hippo pathway, which regulates cell proliferation and apoptosis, presents a therapeutic target for cardiac regeneration. This study explores the efficacy of Lats-IN-1, a LATS1/2 kinase inhibitor targeting the Hippo pathway, as a novel treatment for MI.
Using male C57BL/6 mice subjected to surgically induced MI, we administered Lats-IN-1 and evaluated the effects on cardiac function, infarct size, cardiomyocyte proliferation, and apoptosis through various assays and echocardiographic assessments.
Our results demonstrate that Lats-IN-1 significantly improves cardiac function, as evidenced by enhanced ejection fraction and reduced ventricular dimensions. Additionally, Lats-IN-1 decreased infarct size and apoptosis rates while promoting cardiomyocyte proliferation. These findings suggest that Lats-IN-1 promotes cardiac repair and regeneration.
By modulating the Hippo pathway and reducing apoptosis markers, Lats-IN-1 represents a promising therapeutic strategy for improving outcomes in heart diseases characterized by cardiomyocyte loss. This study highlights the critical role of the Hippo pathway in facilitating cardiac regeneration.
心肌梗死（MI）是心力衰竭的主要原因，其特征是心肌细胞丢失，这严重限制了心脏的再生能力。调节细胞增殖和凋亡的Hippo信号通路是心脏再生的一个治疗靶点。本研究探讨靶向Hippo信号通路的LATS1/2激酶抑制剂Lats-IN-1作为MI新型治疗方法的疗效。
使用通过手术诱导MI的雄性C57BL/6小鼠，给予Lats-IN-1，并通过各种检测和超声心动图评估来评价其对心脏功能、梗死面积、心肌细胞增殖和凋亡的影响。
我们的结果表明，Lats-IN-1显著改善心脏功能，表现为射血分数提高和心室尺寸减小。此外，Lats-IN-1减小了梗死面积并降低了凋亡率，同时促进了心肌细胞增殖。这些发现表明Lats-IN-1促进心脏修复和再生。
通过调节Hippo信号通路并减少凋亡标志物，Lats-IN-1代表了一种有前景的治疗策略，可改善以心肌细胞丢失为特征的心脏病的治疗效果。本研究强调了Hippo信号通路在促进心脏再生中的关键作用。
