{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:42:04Z","timestamp":1760143324838,"version":"build-2065373602"},"reference-count":57,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T00:00:00Z","timestamp":1706572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Australian Government Research Training Scholarship"},{"name":"Evolva SA (Basel, Switzerland)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>There is evidence to suggest that hormonal migraine is associated with altered cerebrovascular function. We aimed to investigate whether the expression of genes related to endothelial function in venous blood (1) might influence cerebrovascular function, (2) differs between hormonal migraineur and non-migraineur women, and (3) changes following resveratrol supplementation. This study utilised data obtained from 87 women (59 hormonal migraineurs and 28 controls) where RNA from venous blood was used to quantify gene expression and transcranial Doppler ultrasound was used to evaluate cerebrovascular function. Spearman\u2019s correlation analyses were performed between gene expression, cerebrovascular function, and migraine-related disability. We compared the expression of genes associated with endothelial function between migraineurs and non-migraineurs, and between resveratrol and placebo. The expression of several genes related to endothelial function was associated with alterations in cerebrovascular function. Notably, the expression of CALCA was associated with increased neurovascular coupling capacity (p = 0.013), and both CALCA (p = 0.035) and VEGF (p = 0.014) expression were associated with increased cerebral blood flow velocity in the overall study population. Additionally, VCAM1 expression correlated with decreased pulsatility index (a measure of cerebral arterial stiffness) (p = 0.009) and headache impact test-6 scores (p = 0.007) in the migraineurs. No significant differences in gene expression were observed between migraineurs and controls, or between placebo and resveratrol treatments in migraineurs. Thus, altering the expression of genes related to endothelial function may improve cerebrovascular function and decrease migraine-related disability.<\/jats:p>","DOI":"10.3390\/ijms25031694","type":"journal-article","created":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T07:49:47Z","timestamp":1706600987000},"page":"1694","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Associations between Cerebrovascular Function and the Expression of Genes Related to Endothelial Function in Hormonal Migraine"],"prefix":"10.3390","volume":"25","author":[{"given":"Jemima S. A.","family":"Dzator","sequence":"first","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW 2308, Australia"},{"name":"School of Pharmacy and Medical Sciences, Griffith University, Gold Coast, QLD 4222, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert A.","family":"Smith","sequence":"additional","affiliation":[{"name":"Genomics Research Centre, Centre for Genomics and Personalised Health, Queensland University of Technology, Brisbane, QLD 4059, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4320-1043","authenticated-orcid":false,"given":"Kirsten G.","family":"Coupland","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW 2308, Australia"},{"name":"Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6546-7742","authenticated-orcid":false,"given":"Peter R. C.","family":"Howe","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW 2308, Australia"},{"name":"Adelaide Medical School, University of Adelaide, Adelaide, SA 5005, Australia"},{"name":"Centre for Health Research, University of Southern Queensland, Raceview, QLD 4350, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6774-5475","authenticated-orcid":false,"given":"Lyn R.","family":"Griffiths","sequence":"additional","affiliation":[{"name":"Genomics Research Centre, Centre for Genomics and Personalised Health, Queensland University of Technology, Brisbane, QLD 4059, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/s10194-012-0424-y","article-title":"Migraine in women: The role of hormones and their impact on vascular diseases","volume":"13","author":"Sacco","year":"2012","journal-title":"J. Headache Pain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1177\/1756285609335537","article-title":"Menstrual migraine: Therapeutic approaches","volume":"2","author":"Macgregor","year":"2009","journal-title":"Ther. Adv. Neurol. Disord."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1152\/japplphysiol.01095.2005","article-title":"Influence of sex steroid hormones on cerebrovascular function","volume":"101","author":"Krause","year":"2006","journal-title":"J. Appl. Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"165","DOI":"10.3389\/fphys.2012.00165","article-title":"Vascular Aging in Women: Is Estrogen the Fountain of Youth?","volume":"3","author":"Novella","year":"2012","journal-title":"Front. Physiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"694980","DOI":"10.3389\/fneur.2021.694980","article-title":"Cerebrovascular Function in Hormonal Migraine: An Exploratory Study","volume":"12","author":"Dzator","year":"2021","journal-title":"Front. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2977","DOI":"10.1161\/STROKEAHA.109.547901","article-title":"Migraine and biomarkers of endothelial activation in young women","volume":"40","author":"Tietjen","year":"2009","journal-title":"Stroke"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Dzator, J.S.A., Coupland, K.G., and Howe, P.R.C. Exploring the Effects of Resveratrol Supplementation on Cerebrovascular Function in Hormonal Migraineurs: A Pilot Study. IBRO Neurosci. Rep., 2023. in press.","DOI":"10.1016\/j.ibneur.2023.10.005"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Li, H., Xia, N., Hasselwander, S., and Daiber, A. (2019). Resveratrol and Vascular Function. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20092155"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/1129-2377-15-62","article-title":"Genetic association and gene expression studies suggest that genetic variants in the SYNE1 and TNF genes are related to menstrual migraine","volume":"15","author":"Smith","year":"2014","journal-title":"J. Headache Pain"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1080\/14728222.2020.1724285","article-title":"Calcitonin gene-related peptide (CGRP): Role in migraine pathophysiology and therapeutic targeting","volume":"24","author":"Wattiez","year":"2020","journal-title":"Expert. Opin. Ther. Targets"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1152\/physrev.00034.2013","article-title":"Calcitonin gene-related peptide: Physiology and pathophysiology","volume":"94","author":"Russell","year":"2014","journal-title":"Physiol. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Fila, M., Sobczuk, A., Pawlowska, E., and Blasiak, J. (2022). Epigenetic Connection of the Calcitonin Gene-Related Peptide and Its Potential in Migraine. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23116151"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1080\/14740338.2020.1811229","article-title":"CGRP inhibitors for migraine prophylaxis: A safety review","volume":"19","author":"MaassenVanDenBrink","year":"2020","journal-title":"Expert. Opin. Drug Saf."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s11916-019-0768-y","article-title":"CGRP Antagonists for the Treatment of Chronic Migraines: A Comprehensive Review","volume":"23","author":"Urits","year":"2019","journal-title":"Curr. Pain Headache Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"578103","DOI":"10.3389\/fneur.2020.578103","article-title":"\u03b1CGRP-Induced Changes in Cerebral and Systemic Circulation; A TCD Study","volume":"11","author":"Zaletel","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1093\/ajh\/4.7.565","article-title":"Normal Serum Levels of Calcitonin Gene-Related Peptide (CGRP) in Mild to Moderate Essential Hypertension","volume":"4","author":"Schifter","year":"1991","journal-title":"Am. J. Hypertens."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1097\/00004872-199210120-00010","article-title":"Plasma calcitonin gene-related peptide levels in patients with various hypertensive diseases","volume":"10","author":"Masuda","year":"1992","journal-title":"J. Hypertens."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2393","DOI":"10.1161\/CIRCULATIONAHA.117.033359","article-title":"Energetics of Blood Flow in Cardiovascular Disease: Concept and Clinical Implications of Adverse Energetics in Patients with a Fontan Circulation","volume":"137","author":"Rijnberg","year":"2018","journal-title":"Circulation"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1042\/cs0810515","article-title":"Changes in blood pressure during the normal menstrual cycle","volume":"81","author":"Dunne","year":"1991","journal-title":"Clin. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"499","DOI":"10.4196\/kjpp.2013.17.6.499","article-title":"Effects of Ovarian Cycle on Hemodynamic Responses during Dynamic Exercise in Sedentary Women","volume":"17","author":"Choi","year":"2013","journal-title":"Korean J. Physiol. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1111\/j.1471-0528.1985.tb02995.x","article-title":"Blood pressure and the menstrual cycle","volume":"92","author":"Greenberg","year":"1985","journal-title":"Br. J. Obs. Gynaecol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1007\/s11916-021-00976-x","article-title":"Hypertension and Migraine: Time to Revisit the Evidence","volume":"25","author":"Wang","year":"2021","journal-title":"Curr. Pain Headache Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.numecd.2022.11.014","article-title":"Association between migraine or severe headache and hypertension among US adults: A cross-sectional study","volume":"33","author":"Zhang","year":"2023","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Jackson, J.L., Kuriyama, A., Kuwatsuka, Y., Nickoloff, S., Storch, D., Jackson, W., Zhang, Z.J., and Hayashino, Y. (2019). Beta-blockers for the prevention of headache in adults, a systematic review and meta-analysis. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0212785"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"03331024231183166","DOI":"10.1177\/03331024231183166","article-title":"The effect of blood pressure lowering medications on the prevention of episodic migraine: A systematic review and meta-analysis","volume":"43","author":"Carcel","year":"2023","journal-title":"Cephalalgia"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.2174\/138945010791591395","article-title":"Vascular endothelial growth factor as an anti-angiogenic target for cancer therapy","volume":"11","author":"Niu","year":"2010","journal-title":"Curr. Drug Targets"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1016\/S0008-6363(01)00344-3","article-title":"Genetic augmentation of nitric oxide synthase increases the vascular generation of VEGF","volume":"51","author":"Jozkowicz","year":"2001","journal-title":"Cardiovasc. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1161\/HYPERTENSIONAHA.120.16454","article-title":"Mechanisms Underlying Vascular Endothelial Growth Factor Receptor Inhibition-Induced Hypertension: The HYPAZ Trial","volume":"77","author":"McGeoch","year":"2021","journal-title":"Hypertension"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1161\/HYPERTENSIONAHA.117.10271","article-title":"Mechanisms of VEGF (Vascular Endothelial Growth Factor) Inhibitor-Associated Hypertension and Vascular Disease","volume":"71","author":"Pandey","year":"2018","journal-title":"Hypertension"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Troncoso, M.F., Ortiz-Quintero, J., Garrido-Moreno, V., Sanhueza-Olivares, F., Guerrero-Moncayo, A., Chiong, M., Castro, P.F., Garc\u00eda, L., Gabrielli, L., and Corbal\u00e1n, R. (2021). VCAM-1 as a predictor biomarker in cardiovascular disease. Biochim. Et Biophys. Acta (BBA)\u2014Mol. Basis Dis., 1867.","DOI":"10.1016\/j.bbadis.2021.166170"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1253\/circj.CJ-16-0058","article-title":"Deregulation of Soluble Adhesion Molecules in Resistant Hypertension and Its Role in Cardiovascular Remodeling","volume":"80","author":"Ritter","year":"2016","journal-title":"Circ. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"21","DOI":"10.5830\/CVJA-2014-060","article-title":"Circulating adhesion molecules and arterial stiffness","volume":"26","author":"Kilic","year":"2015","journal-title":"Cardiovasc. J. Afr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1152\/japplphysiol.00793.2021","article-title":"Six-month longitudinal tracking of arterial stiffness and blood pressure in young adults following SARS-CoV-2 infection","volume":"132","author":"Szeghy","year":"2022","journal-title":"J. Appl. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"804","DOI":"10.5551\/jat.38836","article-title":"Soluble Vascular Cell Adhesion Molecules May be Protective of Future Cardiovascular Disease Risk: Findings from the PREVEND Prospective Cohort Study","volume":"24","author":"Kunutsor","year":"2017","journal-title":"J. Atheroscler. Thromb."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1182\/blood-2004-09-3417","article-title":"VCAM-1 expression in adult hematopoietic and nonhematopoietic cells is controlled by tissue-inductive signals and reflects their developmental origin","volume":"106","author":"Ulyanova","year":"2005","journal-title":"Blood"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e001267","DOI":"10.1161\/JAHA.114.001267","article-title":"Depletion of B-cells with rituximab improves endothelial function and reduces inflammation among individuals with rheumatoid arthritis","volume":"3","author":"Hsue","year":"2014","journal-title":"J. Am. Heart Assoc."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Henein, M.Y., Vancheri, S., Longo, G., and Vancheri, F. (2022). The Role of Inflammation in Cardiovascular Disease. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232112906"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1046\/j.1526-4610.2001.111006129.x","article-title":"Deficiency of tumor necrosis factor alpha in a subclass of menstrual migraineurs","volume":"41","author":"Mueller","year":"2001","journal-title":"Headache"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1177\/0333102416668659","article-title":"The influence of migraine and female hormones on capsaicin-induced dermal blood flow","volume":"37","author":"Ibrahimi","year":"2017","journal-title":"Cephalalgia"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/j.clinbiochem.2004.03.013","article-title":"Optimizing RNA extraction yield from whole blood for microarray gene expression analysis","volume":"37","author":"Wang","year":"2004","journal-title":"Clin. Biochem."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Brkljaci\u0107, J., Tani\u0107, N., Milutinovi\u0107, D.V., Elakovi\u0107, I., Jovanovi\u0107, S.M., Perisi\u0107, T., Dundjerski, J., and Mati\u0107, G. (2010). Validation of endogenous controls for gene expression studies in peripheral lymphocytes from war veterans with and without PTSD. BMC Mol. Biol., 11.","DOI":"10.1186\/1471-2199-11-26"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e3726","DOI":"10.7717\/peerj.3726","article-title":"Identification of reference genes in blood before and after entering the plateau for SYBR green RT-qPCR studies","volume":"5","author":"Xiao","year":"2017","journal-title":"PeerJ"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Dzator, J.S.A., Howe, P.R.C., Coupland, K.G., and Wong, R.H.X. (2022). A Randomised, Double-Blind, Placebo-Controlled Crossover Trial of Resveratrol Supplementation for Prophylaxis of Hormonal Migraine. Nutrients, 14.","DOI":"10.3390\/nu14091763"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/0333102417738202","article-title":"Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition","volume":"38","author":"Olesen","year":"2018","journal-title":"Cephalalgia"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1177\/0333102410379890","article-title":"Validation of the Headache Impact Test (HIT-6\u2122) across episodic and chronic migraine","volume":"31","author":"Yang","year":"2011","journal-title":"Cephalalgia"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S0304-3959(00)00305-5","article-title":"Validity of the Migraine Disability Assessment (MIDAS) score in comparison to a diary-based measure in a population sample of migraine sufferers","volume":"88","author":"Stewart","year":"2000","journal-title":"Pain"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1046\/j.1526-4610.2000.00030.x","article-title":"Validity and reliability of the migraine-specific quality of life questionnaire (MSQ Version 2.1)","volume":"40","author":"Martin","year":"2000","journal-title":"Headache"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1212\/WNL.0b013e31826170ce","article-title":"Endothelial progenitor cells: A new key for endothelial dysfunction in migraine","volume":"79","author":"Sobrino","year":"2012","journal-title":"Neurology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.jneuroim.2005.10.005","article-title":"The importance of cytokines, chemokines and nitric oxide in pathophysiology of migraine","volume":"171","author":"Fidan","year":"2006","journal-title":"J. Neuroimmunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/s10194-021-01271-1","article-title":"Migraine and neuroinflammation: The inflammasome perspective","volume":"22","author":"Kursun","year":"2021","journal-title":"J. Headache Pain"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"233","DOI":"10.3389\/fncel.2018.00233","article-title":"Vascular Contributions to Migraine: Time to Revisit?","volume":"12","author":"Mason","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"771","DOI":"10.4103\/1735-1995.168384","article-title":"Endothelial dysfunction state in migraine headache and neutrally mediated syncope in children and young adults","volume":"20","author":"Sabri","year":"2015","journal-title":"J. Res. Med. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1016\/j.ajpath.2019.04.014","article-title":"Endothelial Hypoxia-Inducible Factor-1\u03b1 Is Required for Vascular Repair and Resolution of Inflammatory Lung Injury through Forkhead Box Protein M1","volume":"189","author":"Huang","year":"2019","journal-title":"Am. J. Pathol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1042\/CS20080196","article-title":"Role of TNF-\u03b1 in vascular dysfunction","volume":"116","author":"Zhang","year":"2009","journal-title":"Clin. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1161\/01.ATV.16.8.1000","article-title":"Interleukin-1\u03b2 in Coronary Arteries of Patients with Ischemic Heart Disease","volume":"16","author":"Galea","year":"1996","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.cardiores.2007.06.004","article-title":"The importance of endothelin-1 for vascular dysfunction in cardiovascular disease","volume":"76","author":"Pernow","year":"2007","journal-title":"Cardiovasc. Res."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Didion, S.P. (2017). Cellular and Oxidative Mechanisms Associated with Interleukin-6 Signaling in the Vasculature. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18122563"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/3\/1694\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:51:44Z","timestamp":1760104304000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/3\/1694"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,30]]},"references-count":57,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["ijms25031694"],"URL":"https:\/\/doi.org\/10.3390\/ijms25031694","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2024,1,30]]}}}