INTERACTOME CHARACTERISTICS OF MORPHOFUNCTIONAL SYSTEM CONDUIT-ATERY ARTERIO-ARTERIAL CONTINUUM DURING IN MODELING IN SILICO

Highlights The morphofunctional conduit-artery system as a surgical connection between the bypass graft and the coronary artery exists in two forms – arterio-arterial and venous-arterial continuum. Coronary artery bypass grafting with autogenous arterial grafts shows the most effective results, this technique relies on the use of patient`s arteries as bypass grafts. The studied interactome of the endothelium of two connected vessels in the arterio-arterial continuum provides a fundamental justification of the high efficiency of this type of bypass. Abstract Background. Alterations in conduits and coronary arteries, which lead to the unacceptable frequency of major adverse cardiovascular events after coronary artery bypass graft surgery, are often determined by endothelial dysfunction. This pathological process may be less pronounced when using autogenous arterial grafts, since the connection of one artery to another is associated with a large number of similar categories of proteome and transcriptome of endothelial cells (EC) of these vessels. At the same time, it remains unclear what constitutes the interactome of this compound, which is based on the interaction of differentially expressed genes and proteins that reflect the structural and functional heterogeneity of various ECs and can influence the biological congruence of the arterio-arterial continuum. Aim. To characterize an interactome of human coronary artery ECs (HCAEC) and human internal thoracic artery ECs (HITAEC) for biological congruence of arterio-arterial continuum assessment. Methods. The study involved commercial culture of human primary HCAEC and HITAEC. Physiological expression was evaluated by transcriptomic and proteomic profiling using RNA sequencing and ultra-high performance liquid chromatography-mass spectrometry, respectively. Bioinformatics analysis of transcriptomic and proteomic data was conducted using the Gene Ontology, Reactome, UniProtKB, and KEGG databases. Interactome was analyzed and characterized during modeling in silico . Results. Most of the protein-protein and gene-gene interaction categories in HCAEC and HITAEC were responsible for the structural and functional maintenance of the endothelial monolayer and basement membrane. This was expressed in such categories as intercellular junctions (tight, anchor, focal, gap junctions, cell junction assembly, cell-substrate junction), cell adhesion (cell and intercellular adhesion and its regulation) and matrix (cell-matrix junction, cell-matrix contact). Moreover, such interactions have been associated with vascular formation (vascular morphogenesis and development, angiogenesis, regulation of angiogenesis, sprouting angiogenesis, VEGF signaling pathway, regulation of VEGF production, transcription and translation of pre-NOTCH, NOTCH signaling), EC proliferation (development, differentiation and migration of EC), formation of elastic fibers (molecules associated with elastic fibers, formation of elastic fibers, assembly of elastic fibers), NO biosynthesis and its regulation (stimulation of NO guanylate cyclase, NO-mediated signal transduction, regulation of the NOS biosynthesis process, regulation of NOS activity). Conclusions. Datasets associated with interactions between differentially expressed proteins and genes of HCAEC and HITAEC are characterized by significant enrichment of arterial homeostasis pathways due to heterogenic cells` coherent structural and functional effects upon contact and synergetic impact on endothelial phenotype, which could possibly be keeping the biological congruence of arterio-arterial continuum in the morphofunctional conduit-artery system for a long time period and thus determine high effectiveness of coronary artery bypass grafting with autogenous arterial grafts.