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Abstract

Objective:

We aimed to study endothelial function with biochemical and ultrasonographic markers and its relation with endothelial progenitor cells (EPCs) in patients with migraine.

Methods:

We performed a case-control study including 47 patients with episodic migraine (International Headache Society 2004 criteria) and 23 control subjects. We analyzed flow-mediated dilation (FMD) in the dominant brachial artery, calcitonin gene−related peptide (CGRP), and vascular endothelial growth factor (VEGF) levels by ELISA, nitric oxide stable metabolites (NOx) by high-performance liquid chromatography, and EPCs in peripheral blood samples, obtained during interictal periods (n = 47) and migraine attacks (n = 19). Frequency, severity, duration of attacks, and time of evolution of migraine were also recorded.

Results:

Patients with migraine showed lower numbers of EPCs than control subjects (9.4 ± 5.0 vs 17.9 ± 6.0 colony forming unit−endothelial cells [CFU-ECs]; p < 0.0001) and higher levels of CGRP (164.2 ± 139.1 vs 37.1 ± 38.5 pg/mL), VEGF (473.4 ± 398.7 vs 72.6 ± 56.6 pg/mL), and NOx (1225.2 ± 466.1 vs 671.9 ± 358.6 μM) (all p < 0.05). During attacks, higher levels for CGRP (298.2 ± 100.3 pg/mL) and NOx (1,656.8 ± 259.5 μM) and lower numbers of EPC (7.2 ± 3.2 CFU-ECs) were observed (all p < 0.05). No changes were found for FMD in interictal periods or during headache. In relation to clinical parameters, EPCs decreased with the time of evolution of migraine (r = −0.592; p < 0.0001).

Conclusions:

Patients with migraine show reduced numbers of EPCs and increased levels of CGRP, NOx, and VEGF than control subjects. Furthermore, EPC counts decrease as migraine progresses in time. These findings suggest altered endothelial function in patients with migraine.

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Supplementary Material

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Information & Authors

Information

Published In

Neurology®
Volume 79Number 5July 31, 2012
Pages: 474-479
PubMed: 22815557

Publication History

Received: November 28, 2011
Accepted: March 19, 2012
Published online: July 18, 2012
Published in print: July 31, 2012

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Disclosure

The authors report no disclosures relevant to the manuscript. Go to Neurology.org for full disclosures.

Authors

Affiliations & Disclosures

Xiana Rodríguez-Osorio, MD, PhD
From the Department of Neurology (X.R.-O., F.M., J.C., R.L.) and Clinical Neurosciences Research Laboratory (T.S., D.B., J.C.), Hospital Clínico Universitario, Universidad de Santiago de Compostela, Santiago de Compostela, Spain.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Tomás Sobrino, PhD
From the Department of Neurology (X.R.-O., F.M., J.C., R.L.) and Clinical Neurosciences Research Laboratory (T.S., D.B., J.C.), Hospital Clínico Universitario, Universidad de Santiago de Compostela, Santiago de Compostela, Spain.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
David Brea, PhD
From the Department of Neurology (X.R.-O., F.M., J.C., R.L.) and Clinical Neurosciences Research Laboratory (T.S., D.B., J.C.), Hospital Clínico Universitario, Universidad de Santiago de Compostela, Santiago de Compostela, Spain.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Francisco Martínez, MD, PhD
From the Department of Neurology (X.R.-O., F.M., J.C., R.L.) and Clinical Neurosciences Research Laboratory (T.S., D.B., J.C.), Hospital Clínico Universitario, Universidad de Santiago de Compostela, Santiago de Compostela, Spain.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
José Castillo, MD, PhD
From the Department of Neurology (X.R.-O., F.M., J.C., R.L.) and Clinical Neurosciences Research Laboratory (T.S., D.B., J.C.), Hospital Clínico Universitario, Universidad de Santiago de Compostela, Santiago de Compostela, Spain.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Rogelio Leira, MD, PhD
From the Department of Neurology (X.R.-O., F.M., J.C., R.L.) and Clinical Neurosciences Research Laboratory (T.S., D.B., J.C.), Hospital Clínico Universitario, Universidad de Santiago de Compostela, Santiago de Compostela, Spain.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE

Notes

Study funding: Supported in part by grants from the Spanish Ministry of Science and Innovation (SAF2008–00737) and Fondo de Investigaciones Sanitarias, Instituto Salud Carlos III (RETICS-RD06/0026), and Xunta de Galicia (Consellería de Industria 10PXIB918282PR and Consellería de Sanidade PS09/32). Xiana Rodríguez-Osorio is the recipient of a fellowship from Instituto de Salud Carlos III of the Spanish Ministry of Science and Innovation (Ayudas para contratos de formación en investigación Río Hortega).
Correspondence & reprint requests to Dr. Leira: [email protected]

Author Contributions

R. Leira and J. Castillo conceived and designed the research, analyzed and interpreted the data, and handled funding and supervision. X. Rodríguez-Osorio and R. Leira drafted the manuscript. J. Castillo performed statistical analysis. T. Sobrino and F. Martínez helped to analyze and interpret the data and made critical revision to the manuscript for important intellectual content. T. Sobrino and D. Brea acquired, analyzed, and interpreted the biochemical and cellular data and supervised the work. X. Rodríguez-Osorio, F. Martínez, and R. Leira helped to acquire, analyze, and interpret the clinical ultrasonographic data.

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