Key circRNAs, lncRNAs, and mRNAs of ShenQi Compound in Protecting Vascular Endothelial Cells from High Glucose Identified by Whole Transcriptome Sequencing

Abstract

Vascular endothelial cells, which make up the inner wall of blood arteries, are susceptible to damage from oxidative stress and apoptosis caused by hyperglycemia. According to certain reports, noncoding RNAs are involved in controlling oxidative stress and apoptosis. ShenQi Compound (SQC), a traditional herbal remedy, has been successfully treating diabetic vascular disease in China for more than 20 years. Although it is well established that SQC protects the vascular endothelium, the molecular mechanism remains unknown. Goto-Kakizaki rats, spontaneous type II diabetes rats, that consistently consume a high-fat diet were chosen as model animals. Six groups (control group, model group, metformin group, and 7.2 g/kg/d SQC group, 14.4 g/kg/d SQC group, and 28.8 g/kg/d SQC group) were included in this work, 15 rats each group. The approach of administration was gavage, and the same volume (5.0 mL/kg/d) was given in each group, once a day, 12 weeks. The thoracic aortas were removed after the rats were sacrificed. Oxidative reduction profile in thoracic aorta, histopathological observation of thoracic aorta, endothelial cell apoptosis in thoracic aorta, whole transcriptome sequencing, bioinformatic analyses, and qRT-PCR were conducted. As a result, SQC prevented the oxidative stress and apoptosis induced by a high glucose concentration. Under hyperglycemia condition, noncoding RNAs, including 1 downregulated novel circRNA (circRNA.3121), 3 downregulated lncRNAs (Skil.cSep08, Shawso.aSep08-unspliced, and MSTRG.164.2), and 1 upregulated mRNA (Pcdh17), were clearly reverse regulated by SQC. SQC plays a role in protecting vascular endothelial cells from high glucose mainly by mediating ncRNA to inhibit cell apoptosis and oxidative stress.