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Cystatin C is an Independent Risk Factor and Therapeutic Target for Acute Ischemic Stroke

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Abstract

Cystatin C (CysC) has been used as a renal function indicator and a strong predictor of cardiovascular events. In this study, we determined the prognostic value of serum CysC in patients with acute ischemic stroke (AIS) and examined its protective role on ischemic brain injury. First-ever stroke patients (601 cases) and control subjects (325 cases) were recruited. Serum CysC level in patients with AIS were significantly higher than that in controls. Multivariate logistic regression analyses showed that elevated CysC is an independent risk factor of AIS; the odds ratio (95 % confidence interval) was 9.80 (3.12–30.83). The integrated population was divided into quintiles according to serum CysC. Compared with the first quintile, the odds ratios of risk for AIS in fourth quintile and fifth quintile were 1.92 (1.08–3.40) and 2.88 (1.49–5.54), respectively. Serum CysC was not associated with neurological deficits and the location of ischemic area; however, serum CysC in patients decreased after one-week therapy. This was consistent with CysC expression after ischemia/reperfusion injury in a mouse focal ischemia/reperfusion injury model. Exogenous CysC exerted neuroprotective effects by reducing infarct volume in this animal stroke model. Therefore, serum CysC is highly associated with AIS and is an independent prediction marker for AIS. Since our findings demonstrated the protection of exogenous CysC on ischemic brain injury, CysC is a novel and promising therapeutic target for AIS.

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Acknowledgments

This study was supported by the grants from the National Natural Science Foundation of China (81071095, 81120108011, and 81361128010) and the Priority Academic Program Development of Jiangsu Higher Education Institutions of China. The authors declare that they have no conflict of interest.

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Correspondence to Heqing Zhao or Xingshun Xu.

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Bo Yang and Jiangtao Zhu were co-first authors.

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Yang, B., Zhu, J., Miao, Z. et al. Cystatin C is an Independent Risk Factor and Therapeutic Target for Acute Ischemic Stroke. Neurotox Res 28, 1–7 (2015). https://doi.org/10.1007/s12640-015-9522-3

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