Arterial and venous grafting biomaterials in coronary surgery: Integrative multi-omics approach reveals ECM-PI3K-Akt pathway as key regulator of different patency

Background: Biomaterials used as grafts in coronary artery bypass grafting (CABG) surgery are autologous arteries (internal mammary artery [IMA] and radial artery [RA]) and saphenous vein (SV). In this study, we investigated the biological differences among IMA-SV, RA-SV, and IMA-RA comparisons using multi-omics approaches in order to explore new therapeutic targets.

Methods: Trios of the human IMA, RA, and SV (n=72) from the CABG patients were studied using transcriptomics and proteomics. Differential mRNAs/proteins were validated by multiple reaction monitoring and real-time quantitative PCR in samples from new cohort of patients.

Results: Differentially expressed (DE) RNAs (60 mRNAs, 4 lncRNAs, 2 circRNAs) and 8 proteins in all three comparisons were identified. DE mRNAs and proteins were classified into 4 correlations (non-DE RNAs/non-DEPs, DE RNAs/non-DEPs, non-DE RNAs/DEPs, and DE RNAs/DEPs). Eleven correlated DE mRNAs/DEPs (TSP1, TENA, TENX, VTNC, LAMA4, CO6A3, COMP, ITA1, DAG1, ITA5, and ITA8) were found in ECM-PI3K-Akt pathway, which may play important roles in mediating nitric oxide production, vasodilation, stenosis, angiogenesis, platelet activation, inflammation, oxidative stress, ECM remolding, and atherosclerosis. Importantly, lower TSP1 in IMA or RA than that in SV, lower TENA and LAMA4 in IMA than that in SV or RA, and higher ITA8 in IMA than that in RA may be the reasons of different long-term patency.

Conclusions: ECM-PI3K-Akt mediating nitric oxide with DE mRNAs and proteins may be the major pathway related to the differences among three grafting vessels. This study provides new insights into the biological differences of these biomaterials and may form new therapeutic targets for improving the long-term results of CABG.

Hou Haitao is a research assistant and has been engaged in molecular mechanisms and pharmacological research on cardiovascular diseases including congenital heart disease, coronary heart disease, and valve disease. In recent years, he has conducted many studies about transcriptomics, proteomics, post-translational modifications, and single cell sequencing. At present, he is studying for a doctorate degree in medicine at Peking Union Medical College.