Reduction of Circulating Endothelial Cells in Peripheral Blood of ALS Patients

Reduction of Circulating Endothelial Cells in Peripheral Blood of ALS Patients

Svitlana Garbuzova-Davis, Robert L. Woods, III, Michael K. Louis, Theresa A. Zesiewicz, Nicole Kuzmin-Nichols, Kelly L. Sullivan, Amber M. Miller, Diana G. Hernandez-Ontiveros, Paul R. Sanberg

PLoS ONE 5(5): e10614. doi:10.1371/journal.pone.0010614

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Background
Amyotrophic Lateral Sclerosis (ALS) treatment is complicated by the various mechanisms underlying motor neuron degeneration. Recent studies showed that the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB) are compromised in an animal model of ALS due to endothelial cell degeneration. A later study demonstrated a loss of endothelium integrity in the spinal cords of ALS patients. Since circulating endothelial cells (CECs) in the peripheral blood are associated with endothelium damage, being detached dysfunctional endothelial cells, we hypothesized that CEC levels may reflect endothelium condition in ALS patients.

Methodology/Principal Findings
CEC levels were estimated in whole blood smears from ALS patients with moderate stage (MALS), severe stage (SALS), and healthy controls by CD146 expression using immunocytochemistry. A significant reduction of CECs was detected in MALS and SALS patients.

Conclusions/Significance
CECs did not predict endothelium state in ALS patients; however, endothelial damage and/or impaired endothelium repair may occur in ALS leading to BBB/BSCB dysfunction. Reduced CECs in peripheral blood of ALS patients may indicate different mechanisms of endothelial damage and repair, rather than only detachment of dysfunctional endothelial cells. Although a potential mechanism of CEC reduction is discussed, establishing a reliable indicator of endothelial dysfunction/damage is important for evaluation of BBB/BSCB status in ALS patients during disease progression.

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