Distinct systemic cytokine networks in symptomatic and asymptomatic carotid stenosis

Abstract

Inflammatory processes are crucial in atherosclerosis and atherothrombosis. This study aimed to identify a cytokine-pattern that is associated with plaque-vulnerability or symptomatic state in comprehensively investigated patients with symptomatic (sCS) and asymptomatic carotid stenosis (aCS). Twenty-two patients with sCS and twenty-four patients with aCS undergoing carotid endarterectomy (CEA) were considered. A cytokine-panel was measured in plasma-specimens prior to surgery and at a 90 day follow-up. Doppler-ultrasound detecting microembolic signals (MES) in the ipsilateral middle cerebral artery was performed. Carotid plaques were analysed regarding histopathological criteria of plaque-vulnerability and presence of chemokine receptor CXCR4. Correction for multiple comparisons and logistic regression analysis adjusting for vascular risk factors, grade of stenosis, antithrombotic and statin pretreatment were applied. In sCS-patients higher plasma-levels of Fractalkine (CX3CL1), IFN-α2, IL-1β, IL-2, IL-3, IL-7 were found compared to aCS-patients. CXCR4-expression on inflammatory cells was more evident in sCS- compared to aCS-plaques and was associated with vulnerability-criteria. In contrast, plasma-cytokine-levels were not related to CXCR4-expression or other vulnerability-criteria or MES. However, in both groups distinct inter-cytokine correlation patterns, which persisted at follow-up and were more pronounced in the sCS-group could be detected. In conclusion, we identified a distinct cytokine/chemokine-network in sCS-patients with elevated and closely correlated mediators of diverse functions.

Circulating microRNAs in Symptomatic and Asymptomatic Carotid Stenosis

“…As reported previously, neither the count of MES per hour [median = 0 (IQR: 1) vs. median = 0 (IQR: 1); p = 0.766] nor the histological sum score [median = 2 (IQR: 2.5) vs. median = 2 (IQR: 2); p = 0.517] differed between the patients with sCS and aCS (11).…”

“…In this prospective case-control study, we considered patients with sCS or aCS who have been previously described in a previous work from our group investigating distinct plasma cytokine patterns ( 11 ). The study recruitment took place between July 2017 and June 2018 at the Departments of Neurology and Cardiothoracic-, Transplantation- and Vascular Surgery at Hannover Medical School.…”

“…Since this is the first study investigating circulating miRs in patients with symptomatic or asymptomatic carotid stenosis and, accordingly, no previous data on miR levels in these groups were available, an appropriate sample size calculation could not be performed. However, under the hypothesis that distinct inflammatory miRs might reveal a comparable discriminative ability such as, e.g., IL-1β, based on the results deriving from the previous study ( 11 ), defining α at 0.05 and the statistical power at 0.80, a sample size of n = 22 per group was calculated to reproduce this finding. Thus, it was anticipated that the sample size of this study is appropriate to detect according biomarker differences between the groups.…”

Urinary Proteomics Identifying Novel Biomarkers for the Diagnosis and Phenotyping of Carotid Artery Stenosis

“…Besides, IL2RB is expressed on T cells and NK cells and transfers IL-2 signals (Fernandez et al, 2019). Moreover, previous studies have revealed that high expression of the IL-2 signal was associated with symptomatic CAS (Stauss et al, 2020). GGH is involved in glutamate removal from folate signals in IPA analysis, and overexpression of GGH can lead to more efflux of folate, which might result in folate deficiency (Wani et al, 2012).…”

“…Moreover, phospholipases are associated with the occurrence of cerebrovascular events in CAS patients with high stroke risk ( Zhang et al, 2021 ). The IL-2 level was significantly higher in symptomatic patients than in asymptomatic CAS patients, indicating the potential predictive value of IL-2 signaling in symptomatic CAS ( Stauss et al, 2020 ). In addition, VEGF is critical in the progression of carotid plaque and intraplaque hemorrhage.…”