A proteomics analysis of neointima formation on decellularized vascular grafts reveals regenerative alterations in protein signature

Coronary artery bypass grafting and percutaneous coronary intervention are most frequently performed surgical intervention for relieving consequences of coronary artery disease. In the clinic, there is a strong demand for vascular repair grafts. Neointima, also known as sub-endothelial scars, are frequently formed in the blood arteries as a result of these surgeries. When neointima forms in the presence of stenosis and significantly lowers blood flow, it might become a serious issue. The creation of neointima causes the stenosis and thrombosis of vascular grafts. It is a complicated reaction that greatly impacts how well vascular grafts work. Despite its significant ramifications, little is understood about the mechanisms underpinning neointima development. Studies on the time-resolved proteomic alterations of neointima following tissue engineered vascular grafts (TEVG) replacement are not yet available. Characterizing the various neointima development stages is essential.

In a new study published in the journal Frontiers in Bioengineering and Biotechnology Central South University scientists: Dr. Chunyang Chen, Dr. Ting Lu, Zhongshi Wu, Dr. Xinlong Xie, Dr. Yalin Liu, Dr. Can Huang and Dr. Yuhong Liu  set out to solve some of the mysteries surrounding the early neointima formation following the implantation of small-diameter TEVGs. They conducted extensive proteome neointima following TEVG implantation to identify proteins, networks, and cells most strenuously associated with early neointima development. The study involved elegant experimental techniques including TEVG manufacturing, tissue collection, mass spectrometry, histological profiling, and statistics and bioinformatics.

Proteomics was used in conjunction with a sequential neointima, diverging from the usual emphasis on regenerative grafts. Using this cutting-edge technique, they identified previously unidentified neointima components and provide insightful information about how the neointima develops via three stages of remodeling. The thorough proteomic comparison allowed for the first time a combined examination of proteins and cells with the participation of relevant biological processes during in the early and late phases of neointima formation in a decellularized TEVGs replacement model. According to the authors, the development of a complete protein layer in the arterial lumen should take hours. The author findings demonstrated that most protein compositions concentrated in the neointima at various times were not linked with the amount of plasma proteins. The three-stage neointima tissue’s comparison to current proteomics data produced the following results: Initially, they discovered that the quantity of adsorbed proteins varied considerably over time across all protein data sets. Secondly, protein binding did not just follow a linear relationship with their relative plasma quantity. Finally, electrostatic effects alone did not represent the primary driving factor; neither protein size nor charge significantly influenced the protein fingerprints. They found that neointima maintained significant levels of proteins implicated in platelet activation, coagulation, and inflammation. In our view, the neointima was remodeling; its stage had remained constant after day 7, when the leukocytes disappeared.

Myofibroblasts/fibroblasts or cells resembling SMCs begin to generate new ECM proteins at this stage, when ECM protein alterations in the stable phase of neointima predominately occur after 2 weeks along with histological results. Neointima typically exhibits late-stage regeneration involving cells and ECMs. The research team focused on how host cells react to the biomaterial, how serum proteins adsorb, and how the neointima tissue remodels after graft implantation. The thorough proteomic comparison allowed for the first time a combined examination of proteins and cells with the participation of relevant biological processes during the early and late stages of neointima development in a decellularized TEVGs replacement model. They found for the first time that serum proteins adsorbed and acute inflammatory cell migration are crucial for neointima development following graft implantation in the rabbit abdominal artery replacement model.

In conclusion, Dr. Yuhong Liu  and colleagues demonstrated a relationship between biological components and the vascular graft, offers insights into neointima biological process alterations, and makes it easier to create a useful bioengineered tiny vascular graft for potential therapeutic uses.