RNA Sequencing Analyses in Infants Patients with Coarctation of the Aorta

Background: Coarctation of the aorta (CoA) is a serious innate heart disease. Although surgery results are generally good, some complications such as recoarctation and aortic aneurysm or persistent hypertension were serious threats to patient's health. To better understand the pathology of CoA and its underlying molecular mechanism is particularly important for early diagnosis and preventing the occurrence of its complications. However, the mechanisms of CoA remain unclear, especially for infants.

Methods: RNA sequencing (RNA-seq) was used to identify the differentially expressed genes (DEGs) in vascular tissues of 12 patients with CoA and 10 normal participants form 3- to 34-month-old infants. The characteristic of DEGs were validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunochemical staining (IHC) in vessels of patients with CoA and normal infants.

Results: A total of 2491 DEGs with the false discovery rate less than 0.05(> 1.5-fold, P < 0.05 change) were identified, including 443 upregulated genes and 2048 downregulated genes. The Gene Ontology enrichment analysis showed that 26 out of the 2491 DEGs identified were associated with cardiovascular diseases. These 26 genes were mainly associated with extracellular matrix (ECM) and smooth muscle cells (SMCs) differentiation. Three DEGs, that is, CNN1 (calponin), α-actinin1 and myosin heavy chain 11 MYH11, were validated using qRT-PCR and Western blot analysis. In addition, immunochemical staining showed that calponin and MYH11 were highly expressed on the surface and in the deep layers of the thickened intima respectively.

Conclusion: This study comprehensively characterized the CoA transcriptome. Migration of extracellular matrix (ECM) and smooth muscle cells (SMCs) to the subendothelial space may be the major characteristic of CoA in infants.