title: Alpha2-macroglobulin as a promising biomarker for cerebral small vessel disease in acute ischemic stroke patients.
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.
authors.affiliation: 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.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Nezu
authors.forename: Naohisa
authors.initials: N
authors.lastname: Hosomi
authors.forename: Shiro
authors.initials: S
authors.lastname: Aoki
authors.forename: Kazushi
authors.initials: K
authors.lastname: Deguchi
authors.forename: Hisashi
authors.initials: H
authors.lastname: Masugata
authors.forename: Noriko
authors.initials: N
authors.lastname: Ichihara
authors.forename: Hideo
authors.initials: H
authors.lastname: Ohyama
authors.forename: Toshiho
authors.initials: T
authors.lastname: Ohtsuki
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kohno
authors.forename: Masayasu
authors.initials: M
authors.lastname: Matsumoto
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000150:complications; D002097:C-Reactive Protein / Q000378:metabolism; D059345:Cerebral Small Vessel Diseases / Q000097:blood* / Q000209:etiology*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D012372:ROC Curve; D018709:Statistics, Nonparametric; D020521:Stroke / Q000150:complications* / Q000209:etiology; D000511:alpha-Macroglobulins / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D000511:alpha-Macroglobulins; D002097:C-Reactive Protein