CD40 ligand as a potential biomarker for atherosclerotic instability - PubMed (original) (raw)

CD40 ligand as a potential biomarker for atherosclerotic instability

Jing-Hua Wang et al. Neurol Res. 2013 Sep.

Abstract

Objective: The signaling protein CD40 and its ligand, CD40L, are thought to contribute to atherosclerotic plaque formation and rupture. We sought to determine their utility as markers of cerebral atherosclerosis and neurological dysfunction.

Methods: We recruited 82 patients with acute cerebral infarction (ACI) and classified each as having large-artery atherosclerosis (LAA, 30), small-artery occlusion (36), or cardioaortic embolism (16). We also recruited 17 patients who had carotid artery stenosis (CAS) without stroke and 20 healthy individuals as controls. CD40L expression on peripheral blood monocytes (PBMCs) was detected by direct immunofluorescence with flow cytometry, and serum soluble CD40L (sCD40L) was measured by ELISA.

Results: CD40L expression on PBMCs was highest in the LAA group, followed by that in the CAS group (both P < 0·01 versus control). It was also higher in patients with atherosclerotic infarction than in those without atherosclerosis (P < 0·05). PBMC CD40L expression was sensitive and specific for detecting atherosclerosis and LAA cerebral infarction and was superior to serum C-reactive protein for predicting cerebral atherosclerosis (P < 0·01). Serum sCD40L was higher in patients with ACI than in healthy controls (P < 0·01) or patients with CAS (P < 0·01) and correlated with increased disability on three scales (all P < 0·01).

Conclusions: We conclude that patients with ACI have an upregulated CD40-CD40L system, which could be used as a clinical biomarker for assessing atherosclerotic instability and severity of neurological dysfunction.

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Figures

Figure 1

Figure 1

Detection of CD40L-expressing peripheral blood monocytes by flow cytometry. Monocytes gated by flow cytometry and expression of CD40L were assessed by the mean fluorescence intensity. Green area represents isotype control and red area represents CD40L detection. The _x_-axis represents CD40L fluorescence intensity and the _y_-axis represents the number of blood monocytes. (A) Normal control. (B) Carotid artery stenosis only. (C) Small-artery occlusion infarct. (D) Large-artery atherosclerotic infarct. (E) Cardioaortic cerebral embolism infarct.

Figure 2

Figure 2

Comparisons of CD40L and high-sensitivity C-reactive protein (hs-CRP) between healthy controls and patients with carotid artery stenosis (CAS), small-artery occlusion (SAO), large-artery atherosclerosis (LAA), and cardioaortic embolism (CAE). (A) Mean fluorescence intensity (MFI) of CD40L on peripheral blood monocytes as assessed by flow cytometry. **P<0.01 versus control; ††P<0.01 versus CAS; ##P<0.01 versus SAO or CAE. (B) Serum hs-CRP levels. *P<0.05, **P<0.01 versus control; †P<0.05, ††P<0.01 versus CAS; ##P<0.01 versus SAO or LAA. (C) Serum sCD40L levels. **P<0.01 versus control; †† P<0.01 versus CAS; ##P<0.01 versus SAO.

Figure 3

Figure 3

Correlations between CD40L expression on PBMCs, serum hp-CRP, serum sCD40L, and neurological dysfunction. CD40L expression on PBMCs was positively correlated with NIHSS score (Spearman rho=0.282, P<0.05; A) and negatively correlated with Barthel Index score (Spearman rho=−0.253, P<0.05; B). Serum hs-CRP level was positively correlated with NIHSS score (Spearman rho=0.433, P<0.01; C) and negatively correlated with Barthel Index score (Spearman rho=0.569, P<0.01; D). There was a positive linear correlation between serum sCD40L and NIHSS score (Spearman rho=0.237, P<0.05, E).

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