Vascular endothelial growth factor-A and chemokine ligand (CCL2) genes are upregulated in peripheral blood mononuclear cells in Indian amyotrophic lateral sclerosis patients

Pawan K Gupta,Chandrika Abburi,Akshay Anand,Sudesh Prabhakar,Neel K Sharma

doi:10.1186/1742-2094-8-114

Abstract

BackgroundWe have earlier shown that protein levels of vascular endothelial growth factor-A (VEGF-A) and chemokine ligand-2 (CCL2) were elevated in Indian amyotrophic lateral sclerosis (ALS) patients. Here, we report the mRNA levels of VEGF-A and CCL2 in Indian ALS patients since they display extended survival after disease onset.MethodsVEGF-A and CCL2 mRNA levels were measured in peripheral blood mononuclear cells (PBMCs) of 50 sporadic Indian ALS patients using Real Time Polymerase Chain Reaction (PCR) and compared with normal controls (n = 50). Their levels were adjusted for possible confounders like cigarette smoking, alcohol and meat consumption.ResultsVEGF-A and CCL2 mRNA levels were found to be significantly elevated in PBMCs in ALS patients as compared to controls. PBMCs from definite ALS revealed higher VEGF-A mRNA expression as compared to probable and possible ALS. CCL2 mRNA levels were found to be unaltered when definite, probable and possible ALS were compared. PBMCs from patients with respiratory dysfunction showed much higher VEGF-A and CCL2 elevation when compared to patients without respiratory dysfunction. No association of smoking, alcohol and meat consumption with VEGF-A and CCL2 was observed after analyzing the data with univariate and multivariate analysis.ConclusionVEGF-A and CCL2 mRNA upregulation in PBMCs may have a clinico-pathological/etiological/epidemiological association with ALS pathogenesis. The cross-cultural and cross-ethnic investigations of these molecules could determine if they have any role in enhancing the mean survival time unique to Indian ALS patients.

Highlights

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by selective loss of motor neuron
We recently reported that augmented biofluids vascular endothelial growth factor-A (VEGF-A) and CCL2 protein may be associated with increased survival duration of Indian amyotrophic lateral sclerosis (ALS) patients [9]
Real Time Polymerase Chain Reaction (PCR) indicates that VEGF-A expression is 77fold higher in ALS than controls (Figure 1A; p = 0.0001)

Summary

Introduction

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by selective loss of motor neuron. Indian ALS patients are known to exhibit significantly extended survival duration after disease onset as compared to Western ALS patients [6,7,8]. We recently reported that augmented biofluids VEGF-A and CCL2 protein may be associated with increased survival duration of Indian ALS patients [9]. We measured the mRNA expression of VEGF-A and CCL2 in peripheral blood mononuclear cells (PBMCs) of these patients. We have earlier shown that protein levels of vascular endothelial growth factor-A (VEGF-A) and chemokine ligand-2 (CCL2) were elevated in Indian amyotrophic lateral sclerosis (ALS) patients. We report the mRNA levels of VEGF-A and CCL2 in Indian ALS patients since they display extended survival after disease onset

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