Serum Metabolomic Profiling of In-Stent Neoatherosclerosis Confirmed by Optical Coherence Tomography in a Rabbit Model

Introduction: In-stent neoatherosclerosis (ISNA) leads to late stent thrombosis (LST) and very late stent thrombosis (VLST), which are major limitations of drug-eluting stents (DESs) application. Metabolic heterogeneity among individuals poses challenges for ISNA prevention. Objectives To explore the specific metabolic molecular dysregulation underlying ISNA. Methods After DES implantation in the iliac artery, eight rabbits were received a high cholesterol diet (HCD), while another eight control rabbits were fed a normal diet. Serum samples were collected at baseline and after treatments for untargeted metabolomic analysis. Optical coherence tomography (OCT) and histological examination were used to classify the different outcomes of ISNA progression. Results Among the rabbits fed the HCD, six developed ISNA and were categorized as Group A, while the remaining two rabbits on the HCD without ISNA were classified as Group B. Additionally, eight control rabbits on a normal diet were designated as Group C. Metabolomics analysis detected a total of 36883 metabolic peaks, leading to the identification of 279 metabolites. Dysregulation of 67, 2, and 40 metabolites was observed in Groups A, B, and C, respectively. Eight dysregulated pathways were enriched based on the 67 differential metabolites in the ISNA group. Notably, eight metabolites, including 9-trans-palmitelaidic acid, biliverdin, palmitoleic acid, choline, cystine, pipecolinic acid, histidine, and L-proline, exhibited specific changing trends in the ISNA group compared to Groups B and C. Conclusion This study provides comprehensive insights into the metabolic molecular mechanisms underlying ISNA, and emphasizes the significance of personalized prevention strategies based on individual metabolic profiles.