ApoC‐I and ApoC‐III as potential plasmatic markers to distinguish between ischemic and hemorrhagic stroke

Abstract

Early diagnosis and immediate therapeutic interventions are crucial factors to reduce the damage extent and the risk of death. Currently, the diagnosis of stroke relies on neurological assessment of the patient and neuro-imaging techniques including computed tomography and/or magnetic resonance imaging scan. An early diagnostic marker of stroke, ideally capable to discriminate ischemic from hemorrhagic stroke would considerably improve patient acute management. Using surface-enhanced laser desorption/ionization (SELDI) technology, we aimed at finding new early diagnostic plasmatic markers of stroke. Strong anionic exchange (SAX) SELDI profiles of plasma samples from 21 stroke patients were compared to 21 samples from healthy controls. Seven peaks appeared to be differentially expressed with significant p values (p < 0.05). Proteins were stripped from the SAX chips, separated on a one-dimensional electrophoresis (1-DE) gel and stained using mass spectrometry (MS)-compatible silver staining. Following in-gel tryptic digestion, the peptides were analyzed by MS. Four candidate proteins were identified as apolipoprotein CI (ApoC-I), apolipoprotein CIII (ApoC-III), serum amyloid A (SAA), and antithrombin-III fragment (AT-III fragment). Assessment of ApoC-I and ApoC-III levels in plasma samples using a sandwich enzyme-linked immunosorbent assay (ELISA) allowed to distinguish between hemorrhagic (n = 15) and ischemic (n = 16) stroke (p < 0.001). To the best of our knowledge, ApoC-I and ApoC-III are the first reported plasmatic biomarkers capable to accurately distinguish between ischemic and hemorrhagic stroke in a small number of patients. It requires further investigation in a large cohort of patients.

Blood Biomarkers of Ischemic Stroke

“…In 135 patients, GFAP was able to distinguish ischemic from hemorrhagic stroke with 79% sensitivity and 98% specificity within 6 hours of symptom onset [22]. In a study of 31 patients, apolipoprotein CI and apolipoprotein CIII were shown to distinguish hemorrhagic from ischemic stroke with 94% sensitivity and 87% specificity [23]. In a larger study of 1146 patients, a 4 panel marker (S100B, MMP9, D-dimer and brain natriuretic factor) was able to distinguish ischemic stroke from stroke mimics including hemorrhagic stroke with 85% sensitivity; however, specificity was only 34% [24].…”

Recent advances in blood‐related proteomics

“…Using the same technique, Gerton et al [70] showed that several serum proteins in the molecular weight range of 7500-18 000 Da were able to discriminate ectopic from intrauterine pregnancies. Heart fatty acid binding protein as well as apolipoprotein C-I and C-III have been proposed as potential biological markers for the diagnosis of stroke [71,72]. Interestingly, apolipoprotein C-I and C-III appeared to be the first reported plasmatic biomarkers able to accurately distinguish between ischemic and hemorrhagic stroke within a small number of patients [72].…”

“…Heart fatty acid binding protein as well as apolipoprotein C-I and C-III have been proposed as potential biological markers for the diagnosis of stroke [71,72]. Interestingly, apolipoprotein C-I and C-III appeared to be the first reported plasmatic biomarkers able to accurately distinguish between ischemic and hemorrhagic stroke within a small number of patients [72]. Proteomic analysis of plasma from patients suffering from acute myocardial infarction revealed also modifications of the protein pattern different from that of patients with unstable angina [73].…”

Mining mass spectra for diagnosis and biomarker discovery of cerebral accidents

“…The interested reader can refer to the companion paper [10] in the same volume. In that paper two of the masses given in Table 9, namely 4480 and 6650, were identified as being possibly an antithrombin-III (AT-III) fragment and apolipoproteinC-I (ApoC-I).…”