Sleep disorders have emerged as a widespread public health concern, primarily due to their association with an increased risk of developing cardiovascular diseases. Our previous research indicated a potential direct impact of insufficient sleep duration on cardiac remodeling in children and adolescents. Nevertheless, the underlying mechanisms behind the link between sleep fragmentation (SF) and cardiac abnormalities remain unclear. In this study, we aimed to investigate the effects of SF interventions at various life stages on cardiac structure and function, as well as to identify genes associated with SF-induced cardiac dysfunction. To achieve this, we established mouse models of chronic SF and two-week sleep recovery (SR). Our results revealed that chronic SF significantly compromised left ventricular contractile function across different life stages, leading to alterations in cardiac structure and ventricular remodeling, particularly during early life stages. Moreover, microarray analysis of mouse heart tissue identified two significant modules and nine hub genes (Ddx60, Irf9, Oasl2, Rnf213, Cmpk2, Stat2, Parp14, Gbp3, and Herc6) through protein–protein interaction analysis. Notably, the interactome predominantly involved innate immune responses. Importantly, all hub genes lost significance following SR. The second module primarily consisted of circadian clock genes, and real-time PCR validation demonstrated significant upregulation of Arntl, Dbp, and Cry1 after SF, while subsequent SR restored normal Arntl expression. Furthermore, the expression levels of four hub genes (Ddx60, Irf9, Oasl2, and Cmpk2) and three circadian clock genes (Arntl, Dbp, and Cry1) exhibited correlations with structural and functional echocardiographic parameters. Overall, our findings suggest that SF impairs left ventricular contractile function and ventricular remodeling during early life stages, and this may be mediated by modulation of the innate immune response and circadian rhythm. Importantly, our findings suggest that a short period of SR can alleviate the detrimental effects of SF on the cardiac immune response, while the influence of SF on circadian rhythm appears to be more persistent. These findings underscore the importance of good sleep for maintaining cardiac health, particularly during early life stages.

中文翻译：

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慢性睡眠碎片化会降低左心室收缩功能，并改变小鼠心脏中与先天免疫反应和昼夜节律相关的基因表达

睡眠障碍已成为一个广泛的公共卫生问题，主要是因为它们与患心血管疾病的风险增加有关。我们之前的研究表明，睡眠时间不足对儿童和青少年的心脏重塑有潜在的直接影响。然而，睡眠碎片化（SF）与心脏异常之间联系背后的潜在机制仍不清楚。在本研究中，我们旨在研究不同生命阶段的 SF 干预对心脏结构和功能的影响，并确定与 SF 诱发的心脏功能障碍相关的基因。为了实现这一目标，我们建立了慢性 SF 和两周睡眠恢复 (SR) 的小鼠模型。我们的结果显示，慢性 SF 会显着损害不同生命阶段的左心室收缩功能，导致心脏结构和心室重塑的改变，特别是在生命早期阶段。此外，通过蛋白质-蛋白质相互作用分析，小鼠心脏组织的微阵列分析确定了两个重要模块和九个中心基因（Ddx60、Irf9、Oasl2、Rnf213、Cmpk2、Stat2、Parp14、Gbp3 和 Herc6）。值得注意的是，相互作用组主要涉及先天免疫反应。重要的是，所有 hub 基因在 SR 后都失去了重要性。第二个模块主要由生物钟基因组成，实时 PCR 验证表明 SF 后 Arntl、Dbp 和 Cry1 显着上调，而随后的 SR 恢复了正常的 Arntl 表达。此外，四个枢纽基因（Ddx60、Irf9、Oasl2 和 Cmpk2）和三个昼夜节律时钟基因（Arntl、Dbp 和 Cry1）的表达水平与结构和功能超声心动图参数相关。总体而言，我们的研究结果表明，SF 会损害生命早期阶段的左心室收缩功能和心室重塑，这可能是通过调节先天免疫反应和昼夜节律来介导的。重要的是，我们的研究结果表明，短期的 SR 可以减轻 SF 对心脏免疫反应的有害影响，而 SF 对昼夜节律的影响似乎更持久。这些发现强调了良好的睡眠对于维持心脏健康的重要性，特别是在生命的早期阶段。