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Published on: October 4, 2021
Multi-Omics Profiling of Human Endothelial Cells from the Coronary Artery and Internal Thoracic Artery Reveals
Alexey Frolov1, Arseniy Lobov2, Marsel Kabilov3
1Department of Experimental Medicine, Research Institute for Complex Issues of Cardiovascular Diseases, 6 Sosnovy Boulevard, Kemerovo 650002, Russia.
Insights
Human coronary artery endothelial cells and internal mammary artery endothelial cells share molecular profiles, suggesting synergistic roles in bypass surgery. This finding aids in understanding better outcomes with total arterial revascularization.
Area of Science:
- Cardiovascular Surgery
- Vascular Biology
- Molecular Medicine
Background:
- Coronary artery bypass graft surgery complications often involve endothelial dysfunction.
- Total arterial revascularization using internal thoracic arteries shows improved long-term outcomes compared to saphenous vein grafts.
Purpose of the Study:
- To investigate the molecular profiles of human coronary artery endothelial cells (HCAECs) and human internal mammary artery endothelial cells (HITAECs).
- To determine the transcriptomic and proteomic similarities and differences between HCAECs and HITAECs in the context of bypass surgery.
Main Methods:
- RNA sequencing was employed to analyze transcriptomic signatures.
- Ultra-high performance liquid chromatography-mass spectrometry was used for proteomic analysis.
- Comparative analysis of gene and protein expression profiles between HCAECs and HITAECs.
Main Results:
- Both HCAECs and HITAECs overexpressed genes involved in extracellular matrix (ECM) synthesis, basement membrane assembly, cell-ECM adhesion, intercellular junction organization, and extracellular vesicle secretion.
- HCAECs showed higher enrichment in molecular signatures related to basement membrane construction, collagen biosynthesis, and intercellular junction formation.
- HITAECs exhibited augmented pro-inflammatory signaling, intensive protein and nitrogen compound synthesis, and enhanced ribosome biogenesis, with no specific protein-level markers identified.
Conclusions:
- Despite molecular heterogeneity, HCAECs and HITAECs share significant molecular characteristics relevant to vascular graft function.
- The coherence in differentially expressed molecular categories suggests potential synergistic interactions between these endothelial cell types in bypass surgery.
- Understanding these molecular interactions may contribute to optimizing total arterial revascularization strategies and improving patient outcomes.
Abstract:
Major adverse cardiovascular events occurring upon coronary artery bypass graft surgery are typically accompanied by endothelial dysfunction. Total arterial revascularisation, which employs both left and right internal thoracic arteries instead of the saphenous vein to create a bypass, is associated with better mid- and long-term outcomes. We suggested that molecular profiles of human coronary artery endothelial cells (HCAECs) and human internal mammary artery endothelial cells (HITAECs) are coherent in terms of transcriptomic and proteomic signatures, which were then investigated by RNA sequencing and ultra-high performance liquid chromatography-mass spectrometry, respectively. Both HCAECs and HITAECs overexpressed molecules responsible for the synthesis of extracellular matrix (ECM) components, basement membrane assembly, cell-ECM adhesion, organisation of intercellular junctions, and secretion of extracellular vesicles. HCAECs were characterised by higher enrichment with molecular signatures of basement membrane construction, collagen biosynthesis and folding, and formation of intercellular junctions, whilst HITAECs were notable for augmented pro-inflammatory signaling, intensive synthesis of proteins and nitrogen compounds, and enhanced ribosome biogenesis. Despite HCAECs and HITAECs showing a certain degree of molecular heterogeneity, no specific markers at the protein level have been identified. Coherence of differentially expressed molecular categories in HCAECs and HITAECs suggests synergistic interactions between these ECs in a bypass surgery scenario.
