Reduced circulating endothelial progenitor cells in reversible cerebral vasoconstriction syndrome

BACKGROUND: The pathophysiology of reversible cerebral vasoconstriction syndrome (RCVS) remains elusive. Endothelial dysfunction might play a role, but direct evidence is lacking. This study aimed to explore whether patients with RCVS have a reduced level of circulating circulating endothelial progenitor cells (EPCs) to repair the dysfunctional endothelial vasomotor control. METHODS: We prospectively recruited 24 patients with RCVS within one month of disease onset and 24 healthy age- and sex-matched controls. Flow cytometry was used to quantify the numbers of circulating EPCs, defined as KDR(+)CD133(+), CD34(+)CD133(+), and CD34(+)KDR(+) double-positive mononuclear cells. The Lindegaard index, an index of vasoconstriction, was calculated by measuring the mean flow velocity of middle cerebral arteries and distal extracranial internal carotid arteries via color-coded sonography on the same day as blood drawing. A Lindegaard index of 2 was chosen as the cutoff value for significant vasoconstriction of middle cerebral arteries based on our previous study. RESULTS: Patients with RCVS had a reduced number of CD34(+)KDR(+) cells (0.009 ± 0.006% vs. 0.014 ± 0.010%, p = 0.031) but not KDR(+)CD133(+) cells or CD34(+)CD133(+) EPCs, in comparison with controls. The number of CD34(+)KDR(+) cells was inversely correlated with the Lindegaard index (rs = -0.418, p = 0.047). Of note, compared to controls, patients with a Lindegaard index > 2 (n = 13) had a reduced number of CD34(+)KDR(+) cells (0.007 ± 0.005% vs. 0.014 ± 0.010%, p = 0.010), but those with a Lindegaard index ≤ 2 did not. CONCLUSIONS: Patients with RCVS had reduced circulating CD34(+)KDR(+) EPCs, which were correlated with the severity of vasoconstriction. Endothelial dysfunction might contribute to the pathogenesis of RCVS.