A microRNA profile comparison between thoracic aortic dissection and normal thoracic aorta indicates the potential role of microRNAs in contributing to thoracic aortic dissection pathogenesis

• Published in: Journal of vascular surgery 2011-05, Vol.53 (5), p.1341-1349.e3
• Main Authors: Liao, Mingfang, MD, PhD, Zou, Sili, MD, Weng, Jianfeng, MD, Hou, Lewei, MD, Yang, Lin, MD, Zhao, Zhiqing, MD, Bao, Junmin, MD, Jing, Zaiping, MD
• Format: Article
• Language: English
• Subjects: Adult; Aneurysm, Dissecting - enzymology; Aneurysm, Dissecting - genetics; Aneurysm, Dissecting - pathology; Aortic Aneurysm, Thoracic - enzymology; Aortic Aneurysm, Thoracic - genetics; Aortic Aneurysm, Thoracic - pathology; Biological and medical sciences; Blood and lymphatic vessels; Blotting, Western; Cardiology. Vascular system; Case-Control Studies; China; Cluster Analysis; Computational Biology; Diseases of the aorta; Focal Adhesion Kinase 1 - genetics; Gene Expression Profiling - methods; Gene Regulatory Networks; Humans; Male; MAP Kinase Signaling System - genetics; Medical sciences; MicroRNAs - analysis; Middle Aged; Oligonucleotide Array Sequence Analysis; Reproducibility of Results; Reverse Transcriptase Polymerase Chain Reaction; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Vascular surgery: aorta, extremities, vena cava. Surgery of the lymphatic vessels
• ISSN: 0741-5214; 1097-6809
• DOI: 10.1016/j.jvs.2010.11.113

Objectives Our aim was to identify important microRNAs (miRNAs) that might play an important role in contributing to aortic dissection by conducting a miRNA profile comparison between thoracic aortic dissection (TAD) and normal thoracic aorta. Methods The differentially expressed miRNA profiles of the aortic tissue between TAD patients (n = 6) and age-matched donors without aortic diseases (NA; n = 6) were analyzed by miRNA microarray. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was further performed to verify the expression of 12 selected miRNAs with an increased number of samples (TAD n = 12; NA n = 8). The potential targets of the differentially expressed miRNAs were predicted using computational searches. Bioinformatic analyses of the predicted target genes (gene ontology, pathway and network analysis) were done for further research. Additionally, Western blotting was performed to confirm the bioinformatics findings. Results The miRNA microarray revealed differentially expressed miRNAs between the TAD and NA groups. In the TAD group, 18 miRNAs were upregulated and 56 were downregulated (fold change >2, P < .01). qRT-PCR verified statistically consistent expression of seven selected miRNAs with microarray analysis. Combined with our previous proteomics study, target gene prediction revealed that some miRNAs reciprocally expressed with their targeted proteins. Target gene-related pathway analysis showed a significant change in five pathways in the TAD group compared with the NA group, especially the focal adhesion and the mitogen-activated protein kinase (MAPK) signaling pathways. By further conducting miRNA gene network analysis, we found that the mir-29 and mir-30 families are likely to play a role in the regulation of these two pathways, respectively. Conclusions Our results indicate that miRNAs expression profiles in aortic media from TAD were significantly changed. These results may provide important insights into TAD disease mechanisms. This study also suggests that the focal adhesion and MAPK signaling pathways might play important roles in the pathogenesis of TAD.