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

Objective: 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. Methods: 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). Results: 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 ( p p = 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. Conclusion: 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. GLOSSARY: ACE = angiotensin-converting enzyme; ATR = angiotensin receptor; β-gal = β-galactosidase; BMI = body mass index; CAD = coronary artery disease; CADASIL = cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; CFU = colony-forming unit; EBM = endothelial basal medium; EPC = endothelial progenitor cell; HDL = high-density lipoprotein; HPF = high-power field; IL = interleukin; KDR = kinase-insert domain receptor; LDL = low-density lipoprotein; MA = migraine with aura; MO = migraine without aura; PBS = phosphate-buffered saline; SA-β-gal = senescence-associated β-galactosidase; SDF-1 = stromal cell–derived factor 1; TNF = tumor necrosis factor; TTH = tension-type headache; VEGF = vascular endothelial growth factor.