Key result
RNA-sequencing strongly links a skeletal myofibril assembly gene module to varicose veins.
Why the study?
The etiology and pathogenesis of varicose veins remain not well defined, necessitating transcriptomic analysis to elucidate underlying molecular mechanisms.
Cross-Sectional (n=20)
No
Effect estimate: r = 0.92
p-value: p=1x10^-8
Transcriptomic profiling reveals that inflammatory pathways are down-regulated and skeletal myofibril assembly pathways are altered in varicose veins compared to normal great saphenous veins.
Transcriptomic differences in varicose veins implicate inflammatory and myofibril pathways; leaves open mechanistic drivers pending validation in larger cohorts.
OBJECTIVE: Varicose veins are a common problem worldwide and can cause significant impairments in health-related quality of life, but the etiology and pathogenesis remain not well defined. This study aims to elucidate transcriptomic regulations of varicose veins by detecting differentially expressed genes, pathways and regulator genes. METHODS: We harvested great saphenous veins (GSV) from patients who underwent coronary artery bypass grafting (CABG) and varicose veins from conventional stripping surgery. RNA-Sequencing (RNA-Seq) technique was used to obtain the complete transcriptomic data of both GSVs from CABG patients and varicose veins. Weighted Gene Co-expression network analysis (WGCNA) and further analyses were then carried out with the aim to elucidate transcriptomic regulations of varicose veins by detecting differentially expressed genes, pathways and regulator genes. RESULTS: From January 2015 to December 2016, 7 GSVs from CABG patients and 13 varicose veins were obtained. WGCNA identified 4 modules. In the brown module, gene ontology (GO) analysis showed that the biological processes were focused on response to stimulus, immune response and inflammatory response, etc. Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis showed that the biological processes were focused on cytokine-cytokine receptor interaction and TNF signaling pathway, etc. In the gray module, GO analysis showed that the biological processes were skeletal myofibril assembly related. The immunohistochemistry staining showed that the expression of ASC, Caspase-1 and NLRP3 were increased in GSVs from CABG patients compared with varicose veins. Histopathological analysis showed that in the varicose veins group, the thickness of vascular wall, tunica intima, tunica media and collagen/smooth muscle ratio were significantly increased, and that the elastic fiber/internal elastic lamina ratio was decreased. CONCLUSION: This study shows that there are clear differences in transcriptomic information between varicose veins and GSVs from CABG patients. Some inflammatory RNAs are down-regulated in varicose veins compared with GSVs from CABG patients. Skeletal myofibril assembly pathway may play a crucial role in the pathogenesis of varicose veins. Characterization of these RNAs may provide new targets for understanding varicose veins diagnosis, progression, and treatment.
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Zhang et al. (2019) conducted a cross-sectional in Varicose veins (n=20). Varicose veins vs. Great saphenous veins from CABG patients was evaluated on Correlation of the gray module (skeletal myofibril assembly genes) with varicose vein status (r = 0.92, p=1x10^-8). RNA-sequencing and weighted gene co-expression network analysis identified 333 differentially expressed genes and a skeletal myofibril assembly module highly correlated with varicose veins (r=0.92, P=1x10^-8).
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