Departments of Medicine, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin, 53226, USA.
Centre for Biotechnology, Anna University, Chennai, Tamil Nadu, 600025, India.
Sci Rep. 2019 Oct 25;9(1):15345. doi: 10.1038/s41598-019-51872-9.
Diabetic cardiomyopathy is one of the main causes of heart failure and death in patients with diabetes. There are no effective approaches to preventing its development in the clinic. Long noncoding RNAs (lncRNA) are increasingly recognized as important molecular players in cardiovascular disease. Herein we investigated the profiling of cardiac lncRNA and mRNA expression in type 2 diabetic db/db mice with and without early diabetic cardiomyopathy. We found that db/db mice developed cardiac hypertrophy with normal cardiac function at 6 weeks of age but with a decreased diastolic function at 20 weeks of age. LncRNA and mRNA transcripts were remarkably different in 20-week-old db/db mouse hearts compared with both nondiabetic and diabetic controls. Overall 1479 lncRNA transcripts and 1109 mRNA transcripts were aberrantly expressed in 6- and 20-week-old db/db hearts compared with nondiabetic controls. The lncRNA-mRNA co-expression network analysis revealed that 5 deregulated lncRNAs having maximum connections with differentially expressed mRNAs were BC038927, G730013B05Rik, 2700054A10Rik, AK089884, and Daw1. Bioinformatics analysis revealed that these 5 lncRNAs are closely associated with membrane depolarization, action potential conduction, contraction of cardiac myocytes, and actin filament-based movement of cardiac cells. This study profiles differently expressed lncRNAs in type 2 mice with and without early diabetic cardiomyopathy and identifies BC038927, G730013B05Rik, 2700054A10Rik, AK089884, and Daw1 as the core lncRNA with high significance in diabetic cardiomyopathy.
2 型糖尿病 db/db 小鼠早期糖尿病心肌病模型中心脏长链非编码 RNA 和信使 RNA 的表达谱分析
糖尿病心肌病是糖尿病患者心力衰竭和死亡的主要原因之一。目前临床上尚无有效的方法来预防其发生。长链非编码 RNA（lncRNA）越来越被认为是心血管疾病的重要分子调控因子。在此，我们研究了 2 型糖尿病 db/db 小鼠（伴或不伴早期糖尿病心肌病）心脏中 lncRNA 和 mRNA 表达谱的变化。结果发现，db/db 小鼠在 6 周龄时发生心肌肥厚，但在 20 周龄时出现舒张功能障碍。与非糖尿病对照相比，20 周龄 db/db 小鼠心脏的 lncRNA 和 mRNA 转录本差异显著。与非糖尿病对照相比，6 周龄和 20 周龄 db/db 心脏中有 1479 个 lncRNA 转录本和 1109 个 mRNA 转录本表达异常。lncRNA-mRNA 共表达网络分析显示，与差异表达的 mRNAs 连接最多的 5 个下调的 lncRNA 为 BC038927、G730013B05Rik、2700054A10Rik、AK089884 和 Daw1。生物信息学分析显示，这 5 个 lncRNA 与膜去极化、动作电位传导、心肌细胞收缩以及心肌细胞肌动蛋白丝的运动密切相关。本研究对伴或不伴早期糖尿病心肌病的 2 型糖尿病小鼠中差异表达的 lncRNA 进行了分析，并确定 BC038927、G730013B05Rik、2700054A10Rik、AK089884 和 Daw1 为糖尿病心肌病中具有高意义的核心 lncRNA。
