Fetuin-A and CD40 L plasma levels in acute ischemic stroke: Differences in relation to TOAST subtype and correlation with clinical and laboratory variables

Abstract

a b s t r a c tIntroduction: Accumulating evidence suggests that inflammation plays an important role in the acute phase of ischemic stroke. CD40 L is a well recognized atherosclerotic inflammatory marker, whereas recent evidence suggests a pro-inflammatory role of Fetuin-A. To analyze the role of an inflammatory marker such as CD40 L and of a candidate pro-inflammatory marker such as Fetuin-A in acute stroke we evaluated their serum levels in subjects with acute ischemic stroke and their possible association with other laboratory and clinical variables. Materials and methods:We enrolled 107 consecutive patients with a diagnosis of acute ischemic stroke admitted to the Internal Medicine Department at the University of Palermo between November 2006 and January 2008, and 102 hospitalized control patients without a diagnosis of acute ischemic stroke. Results: Patients with acute ischemic stroke in comparison to control subjects without acute ischemic stroke had significantly higher CD40 L levels and Fetuin-A serum levels. No significant differences in plasma CD40 L or Fetuin-A levels among different TOAST groups were detected. At intragroup (intra-TOAST-subtype) correlation analysis, among subjects classified as lacunar, CD40 L plasma levels were positively correlated with LDL-cholesterol and with diabetes, whereas Fetuin-A was significantly (positively) correlated with hypertension and white blood cell count. Among subjects with LAAS subtype, CD40 L levels were positively correlated with triglyceride plasma levels and Fetuin-A, whereas Fetuin-A levels were positively correlated with LDL-cholesterol. Discussion: Our findings suggest a pro-inflammatory role of Fetuin-A and CD40 L in acute stroke setting. Whether this role should be construed as direct or as a simple expression of a general inflammatory activation will be up to future studies to clarify.

Role of Fetuin-A in Injury and Infection

“…The elevation of circulating fetuin-A levels correlated with an increase not only in LDL-cholesterol levels (Tuttolomondo et al 2010) but also in risk of cardiovascular disorders (Weikert et al 2008). Similarly, serum fetuin-A levels were increased up to 10-fold in cattle following traumatic injury (Dziegielewska et al 1992), suggesting fetuin-A as a positive APP during ischemic or traumatic injury.…”

“…In patients with cerebral ischemic injury (stroke), plasma fetuin-A levels were paradoxically elevated (Weikert et al 2008;Tuttolomondo et al 2010). The elevation of circulating fetuin-A levels correlated with an increase not only in LDL-cholesterol levels (Tuttolomondo et al 2010) but also in risk of cardiovascular disorders (Weikert et al 2008).…”

Serum amyloid A, fetuin-A, and pentraxin-3 levels in patients with ischemic stroke: novel prognostic biomarkers?

“…There is also the contribution of subclinical inflammation. Thus, it is shown that plasma fetuin-A levels predict the risk of AIS (8,9).…”

New prognostic biomarkers in patients with ischemic stroke

“…CD154 is released into blood circulation as soluble CD154 (sCD154) [37] . When sCD154 binding to their cell surface receptor then exhibit proinflammatory and procoagulant properties, due that triggers the expression of interleukin (IL)-1, IL-6, IL-12, TNF-alpha, interferon-gamma [38] , tissue factor [39][40][41][42] , and binding to the glycoprotein IIb/IIIa platelet receptor [43,44] .There have been found a higher CD154 expression in platelet of ischemic stroke patients than in controls subjects [45,46] , higher circulating levels of sCD154 in ischemic stroke patients than in controls subjects [47][48][49][50][51][52][53][54] , and a higher CD154 expression in platelet of ischemic stroke patients with poor functional outcome compared with patients with better outcome [55,56] .In a study by our team were found higher serum levels of sCD154 in MMCAI patients than in healthy subjects [57] . In addition, we found an association between circulating levels of sCD154 and severity of stroke assessed by GCS (p = 0.04) for the first time.…”