Protein post-translational modification crotonylation of TXN and GLO1 in artery and vein grafts for coronary artery surgery

作者：Wentao Sun, Huanxin Chen, Hai‐Tao Hou, Hongmei Xue, Qin Yang, Guo‐Wei He · 发表于：Redox Biology · 年份：2025 · DOI：10.1016/j.redox.2025.103608 · 被引用次数：6 · 研究领域：Peptidase Inhibition and Analysis、Cardiac Valve Diseases and Treatments、Cardiac Structural Anomalies and Repair

A key problem in coronary artery bypass grafting (CABG) is the lower long-term patency of the saphenous vein (SV) compared to internal thoracic artery (ITA). The potential strategies to improve the long-term patency of the vein graft include developing drugs to block unfavorable pathways in the vein and even to change the protein structure of the vein towards arterial structure. It is therefore important to understand the differences of the protein structure between arterial and venous grafts. Using post-translational modification (PTM) proteomics, we systematically investigated differences between ITA and SV with regard to a vascular stenosis-related PTM crotonylation. Crotonylome and PTM crotonylation in paired ITA and SV segments (n = 150) from patients undergoing CABG surgery were performed by proteomics analysis with further validation. To elucidate the underlying mechanisms, we focused on three crotonylated enzymatic proteins with anti-oxidative effects-thioredoxin (TXN), glyoxalase 1 (GLO1), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) - whose crotonylation patterns were systematically investigated. The functional validation was performed using both site-mutation experiments in HEK293 cells and pharmacological inhibitors in ex vivo cultured ITA/SV tissue specimens. Comprehensive crotonyl-proteomics demonstrated 3652 proteins are differentially-expressed and 411 proteins are differentially-crotonylated in ITA/SV segments. In the identified crotonylated proteins,...