Cardiomyocyte apoptosis is a characteristic of a variety of cardiac diseases, including myocardial infarction (MI). Krüppel-like factor 15 (KLF15) is a transcription factor of Krüppel family that plays an important part in cardiovascular diseases. However, the function and the underlying mechanism of KLF15 in MI remain unknown. The expression of KLF15 was downregulated both in ischemic myocardium of MI mice model and hypoxia-treated neonatal rat ventricular myocytes (NRVCs). KLF15 overexpression mediated by adeno-associated virus significantly abrogated the ischemia-induced cardiac dysfunction, increased the survival rate, and reduced infarct size after MI. Meanwhile, KLF15 overexpression dramatically reduced the myocardial apoptosis, regulated apoptosis-related genes, such as Bcl2 and Bax, diminished the activities of caspase-9/3, and inactivated p38/MAPK signaling in the border zone. Similar results were observed in NRVCs exposed to hypoxia. We demonstrated for the first time that KLF15 overexpression could reduce cardiomyocyte apoptosis and improve cardiac dysfunction in MI mice at least partially by inhibiting p38/MAPK signaling pathway.

中文翻译：

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Krüppel 样因子 15 减少涉及调节 p38/MAPK 信号传导的缺血诱导的细胞凋亡

心肌细胞凋亡是包括心肌梗塞（MI）在内的多种心脏病的特征。Krüppel 样因子 15 (KLF15) 是 Krüppel 家族的转录因子，在心血管疾病中起重要作用。然而，KLF15 在 MI 中的功能和潜在机制仍然未知。在 MI 小鼠模型的缺血心肌和缺氧处理的新生大鼠心室肌细胞 (NRVCs) 中，KLF15 的表达均下调。由腺相关病毒介导的 KLF15 过表达显着消除了缺血诱导的心功能不全，提高了存活率，并减少了 MI 后的梗死面积。同时，KLF15过表达显着降低心肌细胞凋亡，调节凋亡相关基因，如Bcl2和Bax，降低caspase-9/3的活性，和在边界区失活的 p38/MAPK 信号。在暴露于缺氧的 NRVC 中也观察到了类似的结果。我们首次证明 KLF15 过表达可以至少部分通过抑制 p38/MAPK 信号通路来减少心肌细胞凋亡并改善 MI 小鼠的心功能不全。