Serum angiogenesis-hypoxia biomarkers in relapsing-remitting multiple sclerosis.

BACKGROUND

Studies have demonstrated that the hypoxia-angiogenic axis is dysregulated in progressive multiple sclerosis (MS), with an upregulation of hypoxic biomarkers with a paradoxical reduction of angiogenic biomarkers. In this study, we postulated that the hypoxia-angiogenic axis would be relatively preserved in relapsing-remitting MS (RRMS; a predominantly neuroinflammatory driven process) as opposed to its progressive counterpart (predominantly neurodegenerative driven).

METHODS

Serum samples were collected from RRMS participants screened for a randomized pilot trial of domperidone as adjunct therapy, prior to initiation of the study drug (n=122), and matched to healthy controls (n=78). Angiogenic factors were measured with a commercially available bead-based multiplex assay and hypoxia biomarkers were measured with a custom bead-based multiplex assay. Publicly available transcriptomic databases of the RRMS brain were utilized to investigation the expression of selected hypoxia/angiogenic markers in the central nervous system (CNS).

RESULTS

Circulating hypoxic markers (hypoxia inducible factor-1-a, heme oxygenase-1, and heat shock protein-90) were increased in the serum and CNS of people with RRMS. Conversely, brain derived neurotrophic factor was reduced. Lysyl oxidase levels correlated with lesion texture (r=(-)0.28) and brain volume (r=(-)0.24). Angiogenic markers were not significantly dysregulated.

CONCLUSION

Hypoxic factors are upregulated in RRMS serum and CNS, while angiogenesis factors are unchanged. This may suggest preservation of the hypoxia-angiogenic axis in RRMS as compared to the dysregulation seen in progressive MS.