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

From the Stroke and Stem Cell Laboratory (S.-T.L., K.C., K.-H.J., D.-H.K., E.-H.K., V.N.C., J.-H.K., W.-S.I., L.K., J.-E.P., H.-J.P., H.-K.P., E.-C.S., S.K.L., M.K., J.-K.R.), Department of Neurology, Clinical Research Institute, Seoul National University Hospital; Program in Neuroscience (S.-T.L., K.C., K.-H.J., H.-K.P., S.K.L., M.K., J.-K.R.), Neuroscience Research Institute of SNUMRC, Seoul National University; Department of Public Health Service (S.-T.L.), Seoul National Hospital; Division of Epidemic Intelligence Service (K.-H.J.), Korea Center for Disease Control and Prevention, Seoul, South Korea; and Department of Neurology (E.-C.S.), Inha University Hospital, Incheon, South Korea.

Address correspondence and reprint requests to Dr. Jae-Kyu Roh or Dr. Manho Kim, Department of Neurology, Seoul National University Hospital, 28, Yongon-Dong, Chongro-Gu, Seoul, 110-744, South Korea rohjk{at}snu.ac.kr or kimmanho{at}snu.ac.kr

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 < 0.001 in TTH vs MO; 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.

Received May 25, 2007. Accepted in final form September 18, 2007.

Supplemental data at www.neurology.org

Editorial, page 1506

e-Pub ahead of print on March 19, 2008, at www.neurology.org.

*The first two authors contributed equally to this work.

Supported by a grant (SC3060) from the Stem Cell Research Center of the 21st Century Frontier Research Program funded by the Ministry of Science and Technology, a grant (A040042) from the Korea Health 21 R&D Project, and a grant (R01-2006-000-10223-0) from the Basic Science and Engineering Foundation Fund, Republic of Korea.

Disclosure: The authors report no conflicts of interest.

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