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Alpha2-macroglobulin as a promising biomarker for cerebral small vessel disease in acute ischemic stroke patients

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Abstract

Alpha2-macroglobulin is a protease inhibitor that enhances procoagulant properties via the neutralization of plasmin, plasminogen activators and metalloproteinases. Additionally, alpha2-macroglobulin is thought to be involved in inflammatory reactions as a carrier protein for interleukin-6 (IL-6). The objective of this study was to evaluate the usefulness of alpha2-macroglobulin as a biomarker for cerebrovascular diseases. Patients with acute ischemic stroke (n = 159; 93 male and 66 female, 71.6 ± 10.3 years) and patients with no previous history of stroke (n = 77; 38 male and 39 female, 70.7 ± 9.5 years) were consecutively enrolled in this study. White matter lesions were assessed via the fluid-attenuated inversion recovery image of magnetic resonance images using the Fazekas classification. The serum alpha2-macroglobulin levels were measured by nephelometry. The serum alpha2-macroglobulin levels at admission in patients with acute ischemic stroke were higher than those in the control patients (230.2 ± 73.7 vs. 205.0 ± 55.8 mg/dl, p = 0.009). The serum alpha2-macroglobulin levels were positively correlated with age and the severity of the white matter lesions (R 2 = 0.048, p < 0.001 and R 2 = 0.058, p < 0.001, respectively), although there was no significant association between serum alpha2-macroglobulin levels and IL-6 levels. In addition, multivariate analysis showed that increased serum alpha2-macroglobulin levels were independently associated with the severity of white matter lesions [standardized partial regression coefficient (β) 0.102, p = 0.026]. Increased serum alpha2-macroglobulin levels might be involved in the pathophysiology of acute ischemic stroke. Furthermore, serum alpha2-macroglobulin levels, which were associated with high-grade white matter lesions, may reflect the chronic pathophysiological condition of cerebral small vessel disease.

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Acknowledgments

We would like to express our gratitude to Kobayashi, Furuno, Sasanishi and Hironaka for their technical assistance. This study was supported in part by research grants from the Smoking Research Foundation, the Tsuchiya Foundation, the Japan Science and Technology Agency and the Japan Heart Foundation.

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Authors and Affiliations

  1. Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan

    Tomohisa Nezu, Naohisa Hosomi, Shiro Aoki, Toshiho Ohtsuki & Masayasu Matsumoto

  2. Department of Internal Medicine, Kagawa University School of Medicine, Kagawa, Japan

    Naohisa Hosomi, Kazushi Deguchi, Hisashi Masugata & Masakazu Kohno

  3. Department of Neurology, National Hospital Takamatsu Medical Center, Kagawa, Japan

    Noriko Ichihara

  4. Department of Strokology, Osaka Neurosurgical Hospital, Kagawa, Japan

    Hideo Ohyama

Authors
  1. Tomohisa Nezu
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  2. Naohisa Hosomi
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  3. Shiro Aoki
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  4. Kazushi Deguchi
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  5. Hisashi Masugata
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  9. Masakazu Kohno
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  10. Masayasu Matsumoto
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Correspondence to Naohisa Hosomi.

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Nezu, T., Hosomi, N., Aoki, S. et al. Alpha2-macroglobulin as a promising biomarker for cerebral small vessel disease in acute ischemic stroke patients. J Neurol 260, 2642–2649 (2013). https://doi.org/10.1007/s00415-013-7040-x

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  • DOI: https://doi.org/10.1007/s00415-013-7040-x

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