The expression of VEGF-A is down regulated in peripheral blood mononuclear cells of patients with secondary progressive multiple sclerosis.

Abstract

BACKGROUND:

Most patients with relapsing-remitting multiple sclerosis (RRMS) eventually enter a secondary progressive (SPMS) phase, characterized by increasing neurological disability. The mechanisms underlying transition to SPMS are unknown and effective treatments and biomarkers are lacking. Vascular endothelial growth factor-A (VEGF-A) is an angiogenic factor with neuroprotective effects that has been associated with neurodegenerative diseases. SPMS has a prominent neurodegenerative facet and we investigated a possible role for VEGF-A during transition from RRMS to SPMS.

METHODOLOGY/PRINCIPAL FINDINGS:

VEGF-A mRNA expression in peripheral blood mononuclear (PBMC) and cerebrospinal fluid (CSF) cells from RRMS (n = 128), SPMS (n = 55) and controls (n = 116) were analyzed using real time PCR. We demonstrate reduced expression of VEGF-A mRNA in MS CSF cells compared to controls (p<0.001) irrespective of disease course and expression levels are restored by natalizumab treatment(p<0.001). VEGF-A was primarily expressed in monocytes and our CSF findings in part may be explained by effects on relative monocyte proportions. However, VEGF-A mRNA expression was also down regulated in the peripheral compartment of SPMS (p<0.001), despite unchanged monocyte counts, demonstrating a particular phenotype differentiating SPMS from RRMS and controls. A possible association of allelic variability in the VEGF-A gene to risk of MS was also studied by genotyping for six single nucleotide polymorphisms (SNPs) in MS (n = 1114) and controls (n = 1234), which, however, did not demonstrate any significant association between VEGF-A alleles and risk of MS.

CONCLUSIONS/SIGNIFICANCE:

Expression of VEGF-A in CSF cells is reduced in MS patients compared to controls irrespective of disease course. In addition, SPMS patients display reduced VEGF-A mRNA expression in PBMC, which distinguish them from RRMS and controls. This indicates a possible role for VEGF-A in the mechanisms regulating transition to SPMS. Decreased levels of PBMC VEGF-A mRNA expression should be further evaluated as a biomarker for SPMS.

• Authors: Ellen Iacobaeus, Petra Amoudruz, Mikael Ström, Mohsen Khademi, Lou Brundin, Jan Hillert, Ingrid Kockum, Vivianne Malmström, Tomas Olsson, Emma Tham, Fredrik Piehl
• Journal: PloS one (PLoS One) Vol. 6 Issue 5 Pg. e19138 (May 06 2011) ISSN: 1932-6203 [Electronic] United States
• PMID: 21573104 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Messenger
• Vascular Endothelial Growth Factor A

Topics

• Adult
• Aged
• Female
• Flow Cytometry
• Humans
• Leukocytes, Mononuclear (metabolism)
• Male
• Middle Aged
• Multiple Sclerosis, Chronic Progressive (genetics)
• Polymerase Chain Reaction
• RNA, Messenger (genetics)
• Vascular Endothelial Growth Factor A (genetics)
• Young Adult