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ECM-related gene expression profile in vascular smooth muscle cells from human saphenous vein and internal thoracic
Tian-xiang Zhu1, Bin Lan, Ling-ying Meng
1Department of Cardiovascular Surgery, Cardiovascular Institute, Affiliated Shantou Hospital of Sun Yat-sen University, Shantou, Guangdong Province 515031, China.
Insights
Vascular smooth muscle cells from saphenous veins show distinct characteristics compared to internal thoracic arteries, indicating a higher potential for migration and restenosis after coronary artery bypass grafting.
Area of Science:
- Cardiovascular Surgery
- Vascular Biology
- Gene Expression Profiling
Background:
- Saphenous vein (SV) grafts have lower long-term patency than internal thoracic artery (ITA) grafts in Coronary Artery Bypass Grafting (CABG).
- Vascular smooth muscle cell (VSMC) phenotype modulation, proliferation, and migration are implicated in vein graft restenosis.
- Understanding differential gene expression in SV and ITA VSMCs is crucial for elucidating restenosis mechanisms and developing gene therapies.
Purpose of the Study:
- To explore the differential gene expression profile in VSMCs derived from SV and ITA.
- To identify key genes and pathways involved in the distinct behavior of SV and ITA VSMCs.
- To provide insights into the molecular basis of vein graft restenosis after CABG.
Main Methods:
- Cultured VSMCs from paired SV and ITA for gene expression analysis.
- Utilized Affymetrix microarrays and quantitative real-time PCR (FQ RT-PCR) for gene expression profiling.
- Employed bioinformatics analysis (DAVID 2.0) to identify differentially expressed genes between SV and ITA VSMCs.
Main Results:
- Gene microarray analysis revealed significant differences in gene expression between SV and ITA VSMCs (1,075 up-regulated, 1,399 down-regulated in SV VSMCs).
- Fourteen extracellular matrix (ECM)-related genes showed differential expression, with several promoting migration being higher in SV VSMCs.
- Plasminogen activator (PLAT) expression was lower in both SV VSMCs and SV tunica media compared to ITA.
Conclusions:
- VSMCs from SV and ITA exhibit distinct phenotypic characteristics.
- The elevated expression of migration-promoting ECM genes in SV VSMCs suggests increased migratory potential.
- Lower PLAT expression in SV tissues and cells implies a predisposition to restenosis following CABG.
Unlabelled:
Currently, Saphenous vein (SV) and internal thoracic artery (ITA) are still the most common graft materials in Coronary Artery Bypass Grafting (CABG) whereas SV graft have a lower long-term patency than ITA. Vascular smooth muscle cells (VSMCs) phenotype conversion, proliferation and migration may play a key role in mechanism of vein graft restenosis. To explore differential gene expression profile in VSMCs from SV and ITA will help to further elucidate the mechanism of VSMCs in vein graft restenosis after CABG and to provide new thread of gene therapy.
Methods:
VSMCs from paired SV and ITA were cultured for experiments of Affymetrix microarrays and verification using FQ RT-PCR, while the database for annotation, visualization and integrated discovery bioinformatics resources (DAVID 2.0) was utilized for bioinformatics analysis of differential gene expression profile between SV VSMCs and ITA VSMCs. RNA of tunica media from SV and ITA segments were extracted for FQ RT-PCR to display differential expression of PLAT RESULTS: 54,613 probe sets were examined by gene microarray experiments. In SV VSMCs, 1,075 genes were up-regulated and 406 of them were higher than two-fold; 1,399 genes were down-regulated and 424 of them were lower than two-fold as compare with ITA VSMCs.14 ECM-related genes differentially expressed were verificated and listed as following: COL4A4, COL11A1, FN1, TNC, THBS, FBLN, MMP3, MMP9, TIMP3, WNT5A, SGCD were higher whereas COL14A1, ELN, PLAT lower in SV VSMCs than ITA VSMCs. In addition, PLAT was lower in tunica media from SV segments than ITA.
Conclusion:
VSMCs from SV and ITA have distinct phenotypes characteristics. Both promoting and inhibiting migration ECM-related genes were higher in VSMCs from SV as compared with ITA, suggesting that VSMCs from SV have more potential migrating capability whereas less PLAT both in SV VSMCs and vascular tissue,implying that SV may prone to be restenosis after CABG.
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