Increase of Serum CXCL16 Level Correlates Well to Microembolic Signals in Acute Stroke Patients with Carotid Artery Stenosis
Introduction
Stroke is a personal, familial and social disaster. In China, ischemic stroke accounts for > 80% of all strokes [1]. The majority of strokes (85–90%) result from cerebral ischemia. In most cases, extra - and intracranial vessel atherosclerotic changes are considered to be responsible for cerebral ischemia. Carotid artery atherosclerosis is a major risk factor for stroke and subsequent cognitive impairment [2]. A sudden failure of cerebral circulation is usually combined with the instability of atherosclerotic plaques. Plaque destabilization is evidenced clinically by the preoperative occurrence of ischemic symptoms and microembolic signals (MES). MES have been considered a readily measurable marker of increased stroke risk [3], [4] and can be detected by transcranial Doppler (TCD) [5].
Accumulating evidence indicates that inflammation is not only a component of atheromatous plaques, which promotes the initiation and evolution of atheroma [6], but, importantly, it also plays a crucial role in the destabilization of vulnerable plaques with consequent thrombosis and distal thromboembolism [7], [8], thus converting chronic atherosclerosis into an thrombo-embolic disorder [9]. Recently, a protein called CXCL16 was discovered. It is a member of inflammatory chemokine superfamily with putative roles in directing leukocyte migration and functioning as a scavenger receptor for oxidized low-density lipoprotein (ox-LDL) and chemotactic properties [10], [11]. A high expression of CXCL16/SR-PSOX mRNA and protein in the plaques of coronary and carotid atherosclerosis was observed, and CXCL16 has been proposed to act as a pathogenic mediator in atherosclerosis [10], [11], [12], [13].
However, the relationship between the circulating levels of soluble CXCL16 and atherosclerotic disorders remains controversial in the clinic. Both decreased and increased CXCL16 levels have been reported in patients with atherosclerotic disorders [14], [15]. Our previous research found that an elevation of serum CXCL16 level correlated well with atherosclerotic ischemic stroke [16]. However, there are no reports about the relationship between the levels of CXCL16 and microembolic signals (MES) in symptomatic carotid artery stenosis. The role of CXCL16 in the destabilization of atheromatous plaques has never been measured in vivo before. The goal of the present study was to investigate the serum levels of CXCL16 in patients with acute ischemic stroke from atherosclerosis of carotid artery to explore whether the circulating levels of CXCL16 correlates to MES and to further evaluate its potential value as a diagnostic biomarker for the destabilization of atheromatous plaques.
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Subjects
A total number of 222 subjects were enrolled in the present study, including 104 controls and 118 consecutive patients with acute ischemic stroke (≤ 3 days) clinically localized to the carotid territory and with an ipsilateral carotid artery stenosis of > 50% by the North American Symptomatic Carotid Endarterectomy Trial criteria on carotid duplex ultrasonography [17]. The work was carried out in accordance with The code of ethics of the world medical association for experiments involving humans.
Statistical analysis of the patients' characteristics
The clinical characteristics of the patients and the controls are shown in Table 1. There were no significant differences in age, gender, active smoking and alcohol abuse between the patients and the controls (p > 0.05). Additionally, no differences were observed in the co-existence between coronary artery disease (CAD) and diabetes between the two groups (p > 0.05). However, significant differences were detected in the history of hypertension between the patients and the controls (p < 0.05). The
Discussion
Substantial studies have indicated that inflammatory processes play a critical role in several aspects of the pathophysiology and disease progression in acute ischemic stroke [20], [21]. Chemokines are important inflammatory mediators that are thought to play an important pathogenic role in atherogenesis and plaque destabilization by activating and directing leukocytes into atherosclerotic lesions [21]. CXCL16, a newly discovered chemokine of the CXC family, has several inflammatory functions,
Acknowledgments
The authors thank Dr. Guirong Sun. for the excellent technical assistance. This study was supported by a grant from the Shandong Province Natural Science Foundation (ZR2011HM087), the Qingdao Science and Technology Program (Grant No.14-2-4-97-jch) and the Qingdao Postdoctoral Application Research Funded Project.
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These authors contributed to the work equally and should be regarded as co-first authors.