Vascular endothelial growth factor-A (VEGF-A) and chemokine ligand-2 (CCL2) in amyotrophic lateral sclerosis (ALS) patients

Abstract

BackgroundVascular endothelial growth factor-A (VEGF-A) and chemokne ligand-2 (CCL2) levels have been examined in Amyotrophic Lateral Sclerosis (ALS) patients in Western countries. We measured these values in North Indian ALS patients, since these patients display considerably enhanced survival duration.MethodsSporadic ALS patients were included on the basis of El Escorial criteria. VEGF-A and CCL2 levels were analyzed in serum and cerebrospinal fluid (CSF) of 50 ALS patients using enzyme linked immunosorbent assay (ELISA) and compared with normal controls. Their levels were adjusted for possible confounders like cigarette smoking, alcohol and meat consumption.ResultsContrary to previous studies, VEGF-A was found to be elevated significantly in serum and CSF in ALS patient population studied. We also found an increase in CCL2 levels in CSF of these ALS patients. Serum and CSF from definite ALS revealed higher VEGF-A as compared to probable and possible ALS. CCL2 was unaltered between definite, probable and possible ALS. Univariate and multivariate analysis revealed a lack of association of smoking, alcohol and meat consumption with VEGF-A and CCL2 levels.ConclusionsVEGF-A upregulation may indicate an activation of compensatory responses in ALS which may reflect or in fact account for increased survival of North Indian ALS patients after disease onset. The intrathecal synthesis of CCL2 suggests the involvement of adult neural stem cells and microglial activation in ALS pathogenesis which needs further investigation.

VEGF levels in CSF and serum in mild ALS patients

“…Neurotrophic factors may improve cellular function and increase neuronal metabolism, which can even lead to restoration of synaptic connections by growth of new axons. VEGF, a kind of neurotrophic factor, has been suggested to restore neuronal function, improve behavioral deficits and prolong the survival in several trails [20][21][22]. In our study, both the CSF and serum VEGF levels were significantly increased in ALS patients than those in controls, consistent with the existing reports [22].…”

“…In our study, both the CSF and serum VEGF levels were significantly increased in ALS patients than those in controls, consistent with the existing reports [22]. It has been observed that elevated levels of VEGF in CSF, serum, and peripheral blood mononuclear cells may account for substantially prolonged life span of Indian ALS patients as compared to their Western counterparts [22][23][24]. Surprisingly, longer survival is shown in Indian ALS patients after onset (~9 year) of ALS [25,26].…”

“…Further, reduced levels of soluble VEGFR1 (sVEGFR1) [4], an inhibitory receptor of VEGF, have been observed in these patients, supporting the neurotrophic nature of VEGF [27]. It has been proposed that the increased levels of VEGF whose upregulation suggests a compensatory response, by virtue of its angiogenic and neurotrophic nature, may contribute to the enhanced mean survival time in the ALS patients [22] since VEGF is an important neuroprotective cytokine protecting neurons against oxidative injury and glutamate-induced toxicity [15,28,29]. The significantly elevated VEGF levels in CSF and serum observed in our study between ALS patients and control subjects may be dependent on the common pathophysiological mechanism.…”

“…VEGF, a kind of neurotrophic factor, has been suggested to restore neuronal function, improve behavioral deficits and prolong the survival in several trails [20][21][22]. In our study, both the CSF and serum VEGF levels were significantly increased in ALS patients than those in controls, consistent with the existing reports [22]. It has been observed that elevated levels of VEGF in CSF, serum, and peripheral blood mononuclear cells may account for substantially prolonged life span of Indian ALS patients as compared to their Western counterparts [22][23][24].…”

A predictive model for amyotrophic lateral sclerosis (ALS) diagnosis

“…Elevated CCL2 protein and mRNA have already been observed in serum and spinal cord autopsy of ALS patients [15]. Likewise, increased serum VEGFA was observed previously [16,17]. Demographic studies have shown that current smokers are at 1.4 to 3-fold increased risk of ALS development as compared to never smokers [18,19], although association of alcohol with development of ALS is still under question.…”