RNA sequencing analyses in infants patients with coarctation of the aorta
Aijun Liu1, Bin Li1, Ming Yang1
1Department of Pediatric Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, An Zhen Rd, Beijing, 100029, China.
Insights
Coarctation of the aorta (CoA) in infants involves changes in extracellular matrix and smooth muscle cells. This study identified key genes linked to cardiovascular disease in CoA patients, offering insights into infant heart development.
Area of Science:
- Cardiovascular Biology
- Developmental Biology
- Genomics
Background:
- Coarctation of the aorta (CoA) is a critical congenital heart defect with potential complications like recoarctation and hypertension.
- Understanding CoA's molecular mechanisms is vital for early diagnosis and preventing adverse outcomes, especially in infants.
- Current knowledge of CoA pathogenesis, particularly in infants, remains limited.
Purpose of the Study:
- To comprehensively characterize the transcriptome of infants with coarctation of the aorta (CoA).
- To identify differentially expressed genes (DEGs) associated with CoA pathology in infants.
- To elucidate the molecular mechanisms underlying CoA in this vulnerable population.
Main Methods:
- RNA sequencing (RNA-seq) was performed on vascular tissues from 12 infants with CoA and 10 controls (3-34 months old).
- Differentially expressed genes (DEGs) were identified and validated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunochemical staining (IHC).
- Gene Ontology enrichment analysis was employed to understand the functional associations of identified DEGs.
Main Results:
- A total of 2491 DEGs were identified, with 443 upregulated and 2048 downregulated genes.
- Gene Ontology analysis revealed 26 DEGs associated with cardiovascular diseases, primarily related to extracellular matrix (ECM) and smooth muscle cell (SMC) differentiation.
- Validation confirmed differential expression of CNN1 (calponin), α-actinin1, and MYH11, with calponin and MYH11 showing specific localization in thickened intima.
Conclusions:
- The study provides a comprehensive transcriptome profile of CoA in infants.
- Migration of ECM and SMCs to the subendothelial space appears to be a key characteristic of infant CoA.
- These findings contribute to understanding CoA pathogenesis and may inform future diagnostic and therapeutic strategies.
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.
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