High mobility group protein AT-hook 1 (HMGA1), an architectural transcription factor, has previously been reportedto play an essential role in architectural remodeling processes. However, its effects on cardiovascular diseases, particularly sepsis-induced cardiomyopathy, have remained unclear. The study aimed to investigate the role of HMGA1 in lipopolysaccharide-induced cardiomyopathy. Mice subjected to lipopolysaccharide for 12 h resulted in cardiac dysfunction. We used an adeno-associated virus 9 delivery system to achieve cardiac-specific expression of the HMGA1 gene in the mice. H9c2 cardiomyocytes were infected with Ad-HMGA1 to overexpress HMGA1 or transfected with si-HMGA1 to knock down HMGA1. Echocardiography was applied to measure cardiac function. RT-PCR was used to detect the transcriptional level of inflammatory cytokines. CD45 and CD68 immunohistochemical staining were used to detect inflammatory cell infiltration and TUNEL staining to evaluate the cardiomyocyte apoptosis, MitoSox was used to detect mitochondrial reactive oxygen species, JC-1 was used todetect Mitochondrial membrane potential. Our findings revealed that the overexpression of HMGA1 exacerbated myocardial inflammation and apoptosis in response to lipopolysaccharide treatment. Additionally, we also observed that H9c2 cardiomyocytes with HMGA1 overexpression exhibited enhanced inflammation and apoptosis upon stimulation with lipopolysaccharide for 12 h. Conversely, HMGA1 knockdown in H9c2 cardiomyocytes attenuated lipopolysaccharide-induced cardiomyocyte inflammation and apoptosis. Further investigations into the molecular mechanisms underlying these effects showed that HMGA1 promoted lipopolysaccharide-induced mitochondrial-dependent cardiomyocyte apoptosis. The study reveals that HMGA1 worsens myocardial inflammation and apoptosis in response to lipopolysaccharide treatment. Mechanically, HMGA1 exerts its effects by regulating the mitochondria-dependent apoptotic pathway.

高迁移率基团蛋白 AT-hook 1 （HMGA1） 是一种结构转录因子，以前曾报道在结构重塑过程中起着重要作用。然而，它对心血管疾病，特别是脓毒症诱导的心肌病的影响仍不清楚。该研究旨在探讨 HMGA1 在脂多糖诱导的心肌病中的作用。小鼠接受脂多糖 12 h 导致心功能不全。我们使用腺相关病毒 9 递送系统在小鼠中实现 HMGA1 基因的心脏特异性表达。用 Ad-HMGA1 感染 H9c2 心肌细胞以过表达 HMGA1 或转染 si-HMGA1 以敲低 HMGA1。超声心动图测量心脏功能。RT-PCR 检测炎性细胞因子的转录水平。CD45 和 CD68 免疫组化染色检测炎性细胞浸润，TUNEL 染色评估心肌细胞凋亡，MitoSox 检测线粒体活性氧，JC-1 检测线粒体膜电位。我们的研究结果显示，HMGA1 的过表达加剧了脂多糖治疗后心肌炎症和细胞凋亡。此外，我们还观察到，过表达 HMGA1 的 H9c2 心肌细胞在用脂多糖刺激 12 小时后表现出增强的炎症和细胞凋亡。相反，H9c2 心肌细胞中的 HMGA1 敲低减轻了脂多糖诱导的心肌细胞炎症和细胞凋亡。对这些作用背后的分子机制的进一步研究表明，HMGA1 促进脂多糖诱导的线粒体依赖性心肌细胞凋亡。 研究表明，HMGA1 在脂多糖治疗后会加重心肌炎症和细胞凋亡。在机械上，HMGA1 通过调节线粒体依赖性凋亡途径发挥作用。