Decreased number and function of endothelial progenitor cells in patients with migraine

Abstract

<b>Objective: </b> Migraine carries an increased risk for cardiovascular and cerebrovascular diseases that cannot be explained by traditional cardiovascular risk factors. The circulating endothelial progenitor cell (EPC) number is a surrogate biologic marker of vascular function, and diminished EPC counts are associated with higher cardiovascular risk. We investigated whether abnormalities in EPC levels and functions are present in migraine patients. <b>Methods: </b> Consecutive headache patients (n =166) were enrolled, including those with tensiontype headache (TTH; n = 74), migraine without aura (MO; n = 67), and migraine with aura (MA; n = 25). EPC colony-forming units in peripheral blood samples and migratory capacity to chemoattractants (stromal cell-derived factor 1 and vascular endothelial growth factor) and cellular senescence levels were assayed in risk factor-matched subjects (n = 6 per group). <b>Results: </b> The TTH group had more cardiovascular risk factors, more headache days, and higher Framingham risk scores than the other two groups. Mean numbers of EPC colony-forming units were 47.8 ± 24.3 in TTH, 20.4 ±22.2 in MO, and 8.6 ± 10.1 in MA patients (<i>p</i> &lt; 0.001 in TTH vs MO; <i>p</i> = 0.001 in MO vs MA). EPC colony counts of normal subjects (n = 37) were not significantly different from those with TTH. Multiple linear regression models identified only MO, MA, and the presence of migraine (MO + MA) as significant predictors of EPC levels. In addition, EPCs from migraine patients (MO and MA) showed reduced migratory capacity and increased cellular senescence compared with EPCs from TTH or normal subjects. <b>Conclusion: </b> Circulating endothelial progenitor cell (EPC) numbers and functions are reduced in migraine patients, suggesting that EPCs can be an underlying link between migraine and cardiovascular risk. <b>GLOSSARY: </b><b>ACE</b>= angiotensin-converting enzyme;<b>ATR</b>= angiotensin receptor;<b>β-gal</b>= β-galactosidase; <b>BMI</b>= body mass index; <b>CAD</b>= coronary artery disease; <b>CADASIL</b>= cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; <b>CFU</b>= colony-forming unit; <b>EBM</b>= endothelial basal medium; <b>EPC</b>= endothelial progenitor cell; <b>HDL</b>= high-density lipoprotein; <b>HPF</b>= high-power field; <b>IL</b>= interleukin; <b>KDR</b>= kinase-insert domain receptor; <b>LDL</b>= low-density lipoprotein; <b>MA</b>= migraine with aura; <b>MO</b>= migraine without aura; <b>PBS</b>= phosphate-buffered saline; <b>SA-β-gal</b>= senescence-associated β-galactosidase; <b>SDF-1</b>= stromal cell–derived factor 1; <b>TNF</b>= tumor necrosis factor; <b>TTH</b>= tension-type headache; <b>VEGF</b>= vascular endothelial growth factor.