Alterations in metabolome and lipidome in patients with in-stent restenosis

ContextIn-stent restenosis (ISR) can lead to blood flow obstruction, insufficient blood supply to the brain, and may even result in serious complications such as stroke. Endothelial cell hyperproliferation and thrombosis are the primary etiologies, frequently resulting in alterations in intravascular metabolism. However, the metabolic changes related to this process are still undermined.ObjectiveWe tried to characterize the serum metabolome of patients with ISR and those with non-restenosis (NR) using metabolomics and lipidomics, exploring the key metabolic pathways of this pathological phenomenon.ResultsWe observed that the cysteine and methionine pathways, which are associated with cell growth and oxidative homeostasis, showed the greatest increase in the ISR group compared to the NR group. Within this pathway, the levels of N-formyl-l-methionine and L-methionine significantly increased in the ISR group, along with elevated levels of downstream metabolites such as 2-ketobutyric acid, pyruvate, and taurocholate. Additionally, an increase in phosphatidylcholine (PC) and phosphatidylserine (PS), as well as a decrease in triacylglycerol in the ISR group, indicated active lipid metabolism in these patients, which could be a significant factor contributing to the recurrence of blood clots after stent placement. Importantly, phenol sulfate and PS(38:4) were identified as potential biomarkers for distinguishing ISR, with an area under the curve of more than 0.85.ConclusionsOur study revealed significant metabolic alterations in patients with ISR, particularly in the cysteine and methionine pathways, with phenol sulfate and PS(38:4) showing promise for ISR identification. Metabolomic and lipidomic analysis showed that patients who developed in-stent restenosis (ISR) had significantly increased expression of L-methionine and N-formyl-l-methionine, and significantly decreased expression of triacylglycerol in their serum. Phenol sulfate and PS(38:4) may be potential biomarkers for the diagnosis of ISR.image