The Surgical Treatment Efficacy Of Takayasu Arteritis With Aorta And Renal Artery Involvement And Study On The Pathogenesis Of Interleukin In Takayasu Arteritis

Objectives:To explore the role of interleukins in the pathogenesis of TAK from the perspectives of blood and tissue,as well as the clinical efficacy of surgical intervention for aortic and renal artery inflammation in TAK.Methods:This study conducted a retrospective analysis of 87 patients with Takayasu arteritis who underwent surgical and/or endovascular interventions on the Aortic and renal artery between August 2016 and August 2022 at Beijing Hospital.Clinical history and surgical data were collected,and regular follow-up was conducted after surgery.Factors influencing disease prognosis were statistically analyzed.All samples in this study were tested using standard procedures at the Beijing hospital Takayasu arteritis(BeTA)biobank.A total of 29 peripheral blood samples were collected,including 13 healthy controls and 16 patients with Takayasu arteritis,and were analyzed using PEA protein profiling.Fourteen samples of abdominal aortic tissue were collected,including 8 from kidney transplant donors as the control group and 6 from Takayasu arteritis patients who underwent bypass surgery as the experimental group,and were subjected to bulk RNA sequencing.Two samples of renal artery tissue underwent single-cell RNA sequencing,and one block of paraffin-embedded tissue was subjected to HE staining and IHC staining.Results:Among the 87 patients,there were 20 males(23.0%)and 67 females(77%),with a male-to-female ratio of 1:3.35,and a median age of 27 years(range,7-59 years).All surgical procedures were completed smoothly,and a total of 19 perioperative complications(21%)occurred,most commonly poor wound healing,followed by neurological events and acute coronary syndrome.Three patients(3.4%)were lost to follow-up,and the remaining 84 patients(96.6%)completed follow-up,with a mean follow-up time of 39.01±30.453 months.Among them,6 patients(7.1%)died,including 1 perioperative death(1.2%)and 5 deaths(6.0%)unrelated to surgery.Seventeen patients(20.2%)had restenosis,10 patients(11.9%)had symptomatic recurrence,and 16 patients(19.0%)underwent repeat intervention.PEA proteomics results showed that IL-6,IL17C,FGF21,and FGF23 were significantly upregulated in Takayasu’s arteritis(p<0.05,Log2 FC>1).Enrichment analysis showed that protein function was mainly enriched in cell chemotaxis and immune response to external stimuli,while molecular function was mainly enriched in activation of chemokines and binding to their receptors.KEGG pathway analysis showed that cytokine receptor interaction,chemokine signaling pathway,hematopoietic cell lineage,rheumatoid arthritis,and Toll-like receptor signaling pathway were significantly upregulated in the Takayasu’s arteritis group.After quality control of transcriptome sequencing of the abdominal aorta,1897 transcripts were found to be significantly differentially expressed between the Takayasu’s arteritis group and the control group(p<0.05,Log2 FC>1),including 1361 transcripts in the Takayasu’s arteritis group and 536 transcripts in the control group.Comparative analysis of pathway enrichment showed that interleukin-10 signaling pathway and interleukin signaling pathway were highly expressed in the Takayasu’s arteritis group,and extracellular matrix formation-related pathways were also upregulated in the Takayasu’s arteritis group.WGCNA and PPI identified 26 core genes highly correlated with clinical phenotypes.We also used single-cell RNA-seq data to deconvolute bulk RNA-seq data and noted that the proportion of smooth muscle cells was higher in our dataset.In addition,immunohistochemical staining confirmed our bioinformatics analysis that IL-6,IL-1R1,and IL-1R2 were highly expressed in TAK.Conclusion:This study revealed the important role of interleukins in the pathogenesis of TAK,and SMCs may also be involved in the late-stage vascular wall remodeling of TAK.