Genome-wide differential expression profiling of lncRNAs and mRNAs associated with early diabetic cardiomyopathy

Tarun Pant,Zeljko J Bosnjak,Xiaowen Bai,Edward B Thorp,Zhi-Dong Ge,Anuradha Dhanasekaran,Ming Zhao,Joseph M Forbess

doi:10.1038/s41598-019-51872-9

Abstract

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.

Highlights

Diabetic cardiomyopathy is one of the main causes of heart failure and death in patients with diabetes
The results of the present study demonstrate that db/db mice have diabetes, obesity, and left ventricular (LV) hypertrophy at 6 weeks of age and develop early diabetic cardiomyopathy (DCM) at 20 weeks of age
The profiling of both Long noncoding RNAs (lncRNA) and mRNA expression is different between db/db mouse hearts without DCM and with early DCM

Summary

Introduction

Diabetic cardiomyopathy is one of the main causes of heart failure and death in patients with diabetes. We investigated the profiling of cardiac lncRNA and mRNA expression in type 2 diabetic db/db mice with and without early diabetic cardiomyopathy. This study profiles differently expressed lncRNAs in type 2 mice with and without early diabetic cardiomyopathy and identifies BC038927, G730013B05Rik, 2700054A10Rik, AK089884, and Daw[1] as the core lncRNA with high significance in diabetic cardiomyopathy. Due to metabolic disturbance, diabetic myocardium develops local inflammation, necrosis, apoptosis, fibrosis, atherosclerosis, and ventricular hypertrophy[4,5] These pathological changes developed in diabetic hearts can lead to cardiac dysfunction in the absence of ischemic heart disease and hypertension, termed diabetic cardiomyopathy (DCM)[5,6]. Using the high-throughput microarray, we investigated the genome-wide expression profiling of deregulated lncRNAs and mRNAs in freshly isolated myocardium from db/db mice with and without DCM. The lncRNAs-mRNAs co-expression networks were built to explore the relationship between lncRNAs and mRNAs

Methods

Results

Conclusion