Cardiac hypertrophy is a common structural remodeling in many cardiovascular diseases. Recently, long non-coding RNAs (LncRNAs) were found to be involved in the physiological and pathological processes of cardiac hypertrophy. In this study, we found that LncRNA KCND1 (LncKCND1) was downregulated in both transverse aortic constriction (TAC)-induced hypertrophic mouse hearts and Angiotensin II (Ang II)-induced neonatal mouse cardiomyocytes. Further analyses showed that the knockdown of LncKCND1 impaired cardiac mitochondrial function and led to hypertrophic changes in cardiomyocytes. In contrast, overexpression of LncKCND1 inhibited Ang II-induced cardiomyocyte hypertrophic changes. Importantly, enhanced expression of LncKCND1 protected the heart from TAC-induced pathological cardiac hypertrophy and improved heart function in TAC mice. Subsequent analyses involving mass spectrometry and RNA immunoprecipitation assays showed that LncKCND1 directly binds to YBX1. Furthermore, overexpression of LncKCND1 upregulated the expression level of YBX1, while silencing LncKCND1 had the opposite effect. Furthermore, YBX1 was downregulated during cardiac hypertrophy, whereas overexpression of YBX1 inhibited Ang II-induced cardiomyocyte hypertrophy. Moreover, silencing YBX1 reversed the effect of LncKCND1 on cardiomyocyte mitochondrial function and its protective role in cardiac hypertrophy, suggesting that YBX1 is a downstream target of LncKCND1 in regulating cardiac hypertrophy. In conclusion, our study provides mechanistic insights into the functioning of LncKCND1 and supports LncKCND1 as a potential therapeutic target for pathological cardiac hypertrophy.

心脏肥大是许多心血管疾病中常见的结构重塑。近年来，人们发现长链非编码RNA（LncRNA）参与心脏肥大的生理和病理过程。在这项研究中，我们发现 LncRNA KCND1 (LncKCND1) 在横主动脉缩窄 (TAC) 诱导的肥大小鼠心脏和血管紧张素 II (Ang II) 诱导的新生小鼠心肌细胞中表达下调。进一步分析表明，LncKCND1 的敲低会损害心脏线粒体功能并导致心肌细胞肥大变化。相反，LncKCND1的过度表达抑制Ang II诱导的心肌细胞肥大变化。重要的是，LncKCND1 表达的增强可以保护心脏免受 TAC 诱导的病理性心脏肥大的影响，并改善 TAC 小鼠的心脏功能。随后的质谱分析和 RNA 免疫沉淀分析表明，LncKCND1 直接与 YBX1 结合。此外，LncKCND1的过度表达会上调YBX1的表达水平，而沉默LncKCND1则会产生相反的效果。此外，YBX1在心脏肥大期间下调，而YBX1的过表达抑制Ang II诱导的心肌细胞肥大。此外，沉默YBX1可逆转LncKCND1对心肌细胞线粒体功能的影响及其在心脏肥大中的保护作用，表明YBX1是LncKCND1调节心脏肥大的下游靶标。总之，我们的研究提供了 LncKCND1 功能的机制见解，并支持 LncKCND1 作为病理性心脏肥大的潜在治疗靶点。