endothelin-1 and Migraine-Disorders

Migraine is the most common neurological disorder and the second most disabling human condition, whose pathogenesis is favored by a combination of genetic, epigenetic, and environmental factors. In recent years, several efforts have been made to identify reliable biomarker(s) useful to monitor disease activity and/or ascertain the response to a specific treatment.. To review the current evidence on the potential biological markers associated with migraine.. A structured search of peer-reviewed research literature was performed by searching major publications databases up to December 2017.. Several circulating biomarkers have been proposed as diagnostic or therapeutic tools in migraine, mostly related to migraine's inflammatory pathophysiological aspects. Nonetheless, their detection is still a challenge for the scientific community, reflecting, at least in part, disease complexity and clinical diagnostic limitations. At the present time, calcitonin generelated peptide (CGRP) represents probably the most promising candidate as a diagnostic and/or therapeutic biomarker, as its plasma levels are elevated during migraine attack and decrease during successful treatment. Other molecules (including some neuropeptides, cytokines, adipokines, or vascular activation markers) despite promising, do not possess the sufficient prerequisites to be considered as migraine biomarkers.. The characterization of migraine-specific biomarkers would be fundamental in a perspective of precision medicine, enabling risk assessment and tailored treatments. However, speculating on the clinical validity of migraine biomarkers may be premature and controlled clinical trials are presently needed to investigate both the diagnostic and therapeutic value of these biomarkers in migraine.

Topics: Adipokines; Biomarkers; C-Reactive Protein; Calcitonin Gene-Related Peptide; Cytokines; Endothelin-1; Humans; Matrix Metalloproteinase 9; Migraine Disorders; Precision Medicine

The pathophysiology underlying the association between migraine and other non-atherosclerotic vascular diseases is largely unknown. Endothelial dysfunction has been proposed as a common link. Besides, endothelial dysfunction is considered as a predictor of structural changes in the arterial walls.. To review the current knowledge about the functional (endothelial dysfunction) and structural (arterial stiffness and atherosclerotic diseases) arterial properties associated with migraine.. Studies of biological markers of endothelial dysfunction in peripheral blood, systemic and cerebral vasoreactivity, arterial stiffness indexes and direct visualization of macroscopic changes in the arterial wall have shown differences between patients with and without migraine, as well as between the different migraine subtypes.. Endothelial dysfunction, as a predictor of structural changes in arteries, has been proposed as an early marker for vascular pathology associated with migraine. In migraine patients there is an increase of biomarkers of endothelial dysfunction, but the correlation with vasoreactivity studies does not allow definite conclusions. Available data do not allow to conclude that migraine is associated with macroscopic alterations outside the cerebral arterial bed.. Patologia arterial en la migraña: disfuncion endotelial y cambios estructurales en la vasculatura cerebral y sistemica.. Introduccion. La fisiopatologia subyacente a la asociacion entre migraña y otras enfermedades vasculares sistemicas no aterotromboticas no se conoce con certeza. La disfuncion endotelial se ha propuesto como nexo comun. A su vez, la disfuncion endotelial se considera como precursora de cambios estructurales en las paredes arteriales. Objetivo. Revisar el conocimiento actual acerca de las alteraciones funcionales (disfuncion endotelial) y estructurales (rigidez arterial y cambios ateroescleroticos) del lecho arterial asociadas a la migraña. Desarrollo. Estudios de marcadores biologicos de disfuncion endotelial en sangre periferica, vasorreactividad sistemica y cerebral, calculo de indices de rigidez arterial y visualizacion directa de cambios macroscopicos en la pared arterial han mostrado diferencias entre pacientes con y sin migraña, asi como entre los distintos subtipos de migraña. Conclusiones. La disfuncion endotelial, como precursora de cambios estructurales a nivel arterial, se postula como sustrato de la patologia vascular asociada a la migraña. La alteracion de marcadores biologicos es sugestiva de disfuncion endotelial en los pacientes con migraña; sin embargo, la correlacion con estudios de vasorreactividad no permite establecer conclusiones definitivas. Los datos disponibles no permiten concluir que la migraña se asocie con alteraciones macroscopicas fuera del lecho arterial cerebral.

Topics: Ankle Brachial Index; Arteries; Brachial Artery; Carotid Intima-Media Thickness; Cell-Derived Microparticles; Cerebral Arteries; Endothelial Cells; Endothelin-1; Endothelium, Vascular; Humans; Manometry; Migraine Disorders; Nitric Oxide; Oxidative Stress; Plaque, Atherosclerotic; Pulse Wave Analysis; Regeneration; Thrombophilia; Vascular Stiffness; Vasodilation

Migraine is a common disabling headache disorder that is conventionally classified according to the presence or absence of aura. The pathogenesis of this disorder entails a complex interplay of neurovascular factors, that trigger reduction of cerebral blood flow followed by reactive vasodilatation. Despite major emphasis has been placed on the investigation of putative biomarkers that could predict response to specific treatments and prophylaxis, less focus has been directed at the association between migraine and erythrocytosis. Erythrocytosis is typically accompanied by hyperviscosity, that is now considered a crucial determinant in the pathogenesis of migraine. The results of some epidemiological investigations are in substantial agreement to confirm the existence of a significant relationship between increased haemoglobin levels and migraine, whereas some case reports have also reported an effective improvement of symptoms after reduction of erythrocyte count by therapeutic venesection. Interesting evidence has recently emerged from the assessment of red blood cell distribution width (RDW), a simple and inexpensive measure of anysocytosis that has been also associated with a variety of ischaemic and thrombotic disorders other than migraine. The aim of this review was to provide an overview of the current clinical and epidemiological evidence linking migraine and erythrocyte biology.

Topics: Brain; Endothelin-1; Epilepsy; Erythrocyte Count; Erythrocyte Indices; Erythrocytes; Hemoglobins; Hemorheology; Humans; Migraine Disorders; Nitric Oxide; Phlebotomy; Polycythemia; Vasoconstriction

The introduction of sumatriptan, a selective 5-HT(1B/1D) agonist, for the treatment of migraine sparked a new era of drug research in this field. Many novel targets have since been developed, and tested in the clinic. The promise of these approaches is to deliver an anti-migraine compound with the optimal efficacy and safety profile. In this chapter, blind alleys in anti-migraine development are discussed. The failing soldiers have included the NK-1 antagonists, some second-generation 5-HT(1B/1D) agonists, CP-122,288, 4991W93, the neurosteroid ganaxolone, selective 5-HT(1F) (LY334370) and 5-HT(1D) agonists (PNU-142,633), and the endothelin-1 antagonist bosentan. Some of these promising targets failed to demonstrate clinical efficacy, while others were stopped for preclinical toxicity.

Topics: Drug Evaluation, Preclinical; Endothelin-1; Humans; Migraine Disorders; Neurokinin-1 Receptor Antagonists; Serotonin Receptor Agonists

Author presents new epidemiological data in prevalence of headaches in children and adolescents. She precises tension headaches and pathogenesis of migraine and reminds difficulties in its differentiation. She points out to endothelin-1 importance in this process.

Topics: Adolescent; Age Distribution; Child; Diagnosis, Differential; Electroencephalography; Endothelin-1; Headache; Humans; Migraine Disorders; Prevalence; Tension-Type Headache

The endothelin family of peptides are extremely potent endogenous vasoconstrictor and pressor agents. Of the 3 isoforms, endothelin-1 is the major isoform produced by the vascular endothelium and is, therefore, likely to be of most importance for regulation of vascular function. Two endothelin receptor subtypes have so far been cloned in mammalian species; ET A, and ET B. Both receptor subtypes are found on smooth muscle cells and mediate the vasoconstrictor and pressor actions of endothelin. The ET B receptor is also found on vascular endothelial cells and mediates endothelin-dependent vasodilatation through release of nitric oxide and prostacyclin. Since their discovery in 1988, the endothelins have been the subject of intense research on their physiological function and potential pathophysiological role in cardiovascular disease. There is now good evidence that endothelin regulates vascular tone and blood pressure, and studies to support the development of endothelin receptor antagonists in conditions associated with chronic vasoconstriction, such as hypertension and heart failure, as well as in vasospastic disorders, such as subarachnoid haemorrhage and Raynaud's disease. There are now a number of selective ET A and combined ET A/B receptor antagonists available for preclinical studies. However, it is still not clear which of these will prove to be of most therapeutic value. Some of these agents are currently being assessed in early phase clinical trials. Endothelin receptor antagonists represent a novel therapeutic approach to a fundamental and newly discovered endogenous vasoconstrictor mechanism. The results of the current clinical trials are awaited with considerable interest.

Topics: Amino Acid Sequence; Animals; Cardiovascular Diseases; Coronary Disease; Endothelin Receptor Antagonists; Endothelin-1; Heart Failure; Humans; Hypertension; Migraine Disorders; Raynaud Disease; Subarachnoid Hemorrhage

To investigate whether intravenously infused provokes migraine aura and migraine headache in migraine patients with aura.. Migraine with aura has been associated with endothelial dysfunction and increased stroke risk. The initiating mechanism of migraine aura symptoms is not known. Experimental provocation of migraine headache using vasoactive peptides has provided tremendous advances in the understanding of migraine pathophysiology but substances that can induce migraine aura have not been identified. Endothelin-1 (ET-1), an endogenous, potent vasoconstrictor peptide released from the vascular endothelium, has been proposed to trigger migraine aura. This hypothesis is based on reports of increased plasma ET-1 levels early during the migraine attacks and the observation that ET-1 applied to the cortical surface potently induces the cortical spreading depolarization, the underlying electrophysiological phenomenon of migraine aura, in animals. Further, endothelial damage due to, for example, carotid puncture and vascular pathology is known to trigger aura episodes.. We investigated whether intravascular ET-1 would provoke migraine aura in patients. Using a two-way crossover, randomized, placebo-controlled, double-blind design, we infused high-dose (8 ng/kg/minutes for 20 minutes) intravenous ET-1 in patients with migraine with typical aura. The primary end-point was the difference in incidence of migraine aura between ET-1 and placebo. Experiments were carried out at a public tertiary headache center (Danish Headache Center, Rigshospitalet Glostrup, Denmark).. Fourteen patients received intravenous ET-1. No patients reported migraine aura symptoms or migraine headache during or up to 24 hours following the ET-1 infusion. Four patients reported mild to moderate headache only on the ET-1 day, 3 patients reported moderate headache on the placebo day, and 1 patient reported mild headache on both days. No serious adverse events occurred during or after infusion.. Provocation of migraine aura by procedures or conditions involving vascular irritation is unlikely to be mediated by ET-1.

Topics: Adolescent; Adult; Cross-Over Studies; Double-Blind Method; Endothelin-1; Female; Humans; Infusions, Intravenous; Male; Migraine Disorders; Migraine with Aura; Young Adult

In a double blind, placebo-controlled study to assess the prophylactic effect of hyperbaric oxygen therapy on migraine, 40 patients were randomly assigned to a treatment group receiving three sessions of hyperbaric oxygen, or a control group receiving three hyperbaric air treatments. The patients were instructed to keep a standardized migraine diary for eight weeks before and after the treatment. Thirty-four patients completed the study. Our primary measure of efficacy was the difference between pre- and post-treatment hours of headache per week. The results show a nonsignificant reduction in hours of headache for the hyperbaric oxygen group compared to the control group. Levels of endothelin-1 in venous blood before and after treatment did not reveal any difference between the hyperbaric oxygen and control groups. We conclude that the tested protocol does not show a significant prophylactic effect on migraine and does not influence the level of endothelin-1 in venous blood.

Topics: Adult; Aged; Endothelin-1; Female; Humans; Hyperbaric Oxygenation; Male; Middle Aged; Migraine Disorders

Dachuanxiong Formula (DCXF) is a classical Chinese medicine prescription and is composed of dried rhizomes from Ligusticum striatum DC. (Chuanxiong Rhizoma) and Gastrodia elata Bl. (Gastrodiae Rhizoma) at the ratio of 4:1 (w/w). It has been used as Chinese medicine prescription for thousands of years. DCXF is used traditionally to treat many diseases, including migraine, atherosclerosis and ischemic stroke.. This study aimed to investigate the effects of DCXF on pain response in migraine mice, and the underlying mechanisms using proteomics and bioinformatics analyses.. DCXF extract was prepared by mixing Chuanxiong Rhizoma and Gastrodiae Rhizoma at a mass ratio of 4:1 (w/w). After extraction, the extract was filtered prior to high performance liquid chromatography (HPLC) analysis. Nitroglycerin (NTG) was used to establish a mouse migraine model, and a behaviour study was conducted by hot plate test. In addition, proteomics and bioinformatics studies were conducted to investigate the mechanisms of DCXF-mediating anti-migraine treatment.. Our results showed that there were significant differences in the latencies between NTG-treated and DCXF low dose- and high doses-treated groups at 30 min after NTG injection, this suggested that DCXF could ameliorate pain response in migraine mice. Besides, the plasma levels of endothelin-1 were also measured. NTG group significantly enhanced the endothelin-1 level compared to the control group. In contrast, DCXF low dose and high dose groups significantly reduced this level compared to NTG group. In addition, the underlying mechanisms were also investigated. Our results demonstrated that the anti-migraine treatment of DCXF was highly associated with fatty acid synthesis, suggesting that DCXF ameliorated pain response through reducing endothelin-1 level and regulating fatty acid synthesis.. The present study revealed the anti-migraine effect of DCXF in migraine mice and provided insights into the mechanisms of DCXF-mediating anti-migraine treatment.

Topics: Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Endothelin-1; Fatty Acids; Female; Male; Mice; Mice, Inbred C57BL; Migraine Disorders; Nitroglycerin

Individuals with migraine present ictal elevation of endothelin-1 levels. Migraine can be subclassified into episodic migraine and chronic migraine. Apart from the inconsistent reports on interictal endothelin-1 levels, most studies did not distinguish between episodic migraine and chronic migraine.. We measured plasma endothelin-1 levels in participants with episodic migraine (n = 87), with chronic migraine (n = 88), and controls (n = 50).. Interictal endothelin-1 levels were not significantly different among participants with episodic migraine, those with chronic migraine, and controls (pg/ml, median and interquartile range, 10.19 [7.76-13.69] vs. 9.25 [6.91-10.73] vs. 9.46 [7.00-14.19],. Interictal plasma endothelin-1 level is an unlikely marker for episodic migraine and chronic migraine.

Topics: Biomarkers; Endothelin-1; Headache; Headache Disorders, Secondary; Humans; Migraine Disorders

There is cumulating evidence that endothelin-1 (ET-1) may play a role in migraine, however controversial findings still impede a conclusion to be drawn. Herein we tested the hypothesis that endothelin ETB receptors are major contributors to migraine-like responses. ET-1, IRL-1620 (selective ETB receptor agonist) or CGRP were injected into the trigeminal ganglion (TG) of female Wistar rats, and the development of periorbital mechanical allodynia was assessed hourly with von Frey hairs. Twenty-four hours later, rats were exposed to an aversive light for 1 h, after which the reactivation of periorbital mechanical allodynia (indicating photic sensitivity) was assessed up to 4 h. Moreover, the effect of systemic Bosentan (ETA/ETB receptors antagonist) or the selective antagonists of ETA (BQ-123) and ETB (BQ-788) receptors injected into the TG were evaluated against CGRP-induced responses. ET-1 and IRL-1620 injection into the TG induced periorbital mechanical allodynia and photic sensitivity. Bosentan attenuated periorbital mechanical allodynia but failed to affect photic sensitivity induced by CGRP. Selective blockade of ETB receptors in the TG fully prevented the development of periorbital mechanical allodynia and photic sensitivity induced by CGRP, but ETA receptor blockade caused only a slight reduction of periorbital mechanical allodynia without affecting photic sensitivity. ETB receptor-operated mechanisms in the TG may contribute to migraine-like responses in female rats.

Topics: Animals; Bosentan; Calcitonin Gene-Related Peptide; Endothelin Receptor Antagonists; Endothelin-1; Endothelins; Female; Hyperalgesia; Migraine Disorders; Peptides, Cyclic; Rats; Rats, Wistar; Receptors, Endothelin

The purpose of this study was to investigate the significance of circulating micro RNAs (miRNAs) in the pathogenesis of reversible cerebral vasoconstriction syndrome (RCVS).. We prospectively recruited 3 independent cohorts of patients with RCVS and age-matched and sex-matched controls in a single medical center. Next-generation small RNA sequencing followed by quantitative polymerase chain reaction (PCR) was used to identify and validate differentially expressed miRNAs, which was cross-validated in migraine patients in ictal stage or interictal stage. Computational analysis was used to predict the target genes of miRNAs, followed by in vitro functional analysis.. We identified a panel of miRNAs including miR-130a-3p, miR-130b-3p, let-7a-5p, let-7b-5p, and let-7f-5p that well differentiated patients with RCVS from controls (area under the receiver operating characteristics curve [AUC] was 0.906, 0.890, and 0.867 in the 3 cohorts, respectively). The abundance of let-7a-5p, let-7b-5p, and let-7f-5p, but not miR-130a-3p nor miR-130b-3p, was significantly higher in patients with ictal migraine compared with that of controls and patients with interictal migraine. Target prediction and pathway enrichment analysis suggested that the transforming growth factor-β signaling pathway and endothelin-1 responsible for vasomotor control might link these miRNAs to RCVS pathogenesis, which was confirmed in vitro by transfecting miRNAs mimics or incubating the patients' cerebrospinal fluid (CSF) in 3 different vascular endothelial cells. Moreover, miR-130a-3p was associated with imaging-proven disruption of the blood-brain barrier (BBB) in patients with RCVS and its overexpression led to reduced transendothelial electrical resistance (ie, increased permeability) in in vitro human BBB model.. We identified the circulating miRNA signatures associated with RCVS, which may be functionally linked to its headache, BBB integrity, and vasomotor function. ANN NEUROL 2021;89:459-473.

Topics: Adult; Blood-Brain Barrier; Capillary Permeability; Case-Control Studies; Cerebrovascular Disorders; Circulating MicroRNA; Computer Simulation; Electric Impedance; Endothelial Cells; Endothelin-1; Female; High-Throughput Nucleotide Sequencing; Human Umbilical Vein Endothelial Cells; Humans; In Vitro Techniques; Male; MicroRNAs; Middle Aged; Migraine Disorders; Reproducibility of Results; Sequence Analysis, RNA; Transforming Growth Factor beta; Vasoconstriction; Vasomotor System

Calcitonin gene-related peptide is recognized as a key player in migraine, yet the mechanisms and sites of calcitonin gene-related peptide action remain unknown. The efficacy of calcitonin gene-related peptide-blocking antibodies as preventative migraine drugs supports a peripheral site of action, such as the trigeminovasculature. Given the apparent disconnect between the importance of vasodilatory peptides in migraine and the prevailing opinion that vasodilation is an epiphenomenon, the goal of this study was to test whether vasodilation plays a role in calcitonin gene-related peptide-induced light aversive behavior in mice.. Systemic mean arterial pressure and light aversive behavior were measured after intraperitoneal administration of calcitonin gene-related peptide and vasoactive intestinal peptide in wild-type CD1 mice. The functional significance of vasodilation was tested by co-administration of a vasoconstrictor (phenylephrine, endothelin-1, or caffeine) with calcitonin gene-related peptide to normalize blood pressure during the light aversion assay.. Both calcitonin gene-related peptide and vasoactive intestinal peptide induced light aversion that was associated with their effect on mean arterial pressure. Notably, vasoactive intestinal peptide caused relatively transient vasodilation and light aversion. Calcitonin gene-related peptide-induced light aversion was still observed even with normalized blood pressure. However, two of the agents, endothelin-1 and caffeine, did reduce the magnitude of light aversion.. We propose that perivascular calcitonin gene-related peptide causes light-aversive behavior in mice by both vasomotor and non-vasomotor mechanisms.

Topics: Animals; Caffeine; Calcitonin Gene-Related Peptide; Endothelin-1; Mice; Migraine Disorders; Photophobia; Vasoactive Intestinal Peptide

This experiment aimed to explore the curative effect of Tuling Wendan Decoction combined with flunarizine on migraine patients and the intervention effect on serum cyclooxygenase-2 (COX-2), endothelin-1 (ET-1), nitric oxide(NO) levels. For this purpose, from January 2019 to January 2020, 96 patients with migraine in our hospital were selected as the research object. Using a simple randomization method, patients who meet the criteria were assigned 1:1, and each patient was assigned a random number, of which the number 1 to 48 were the observation group, and the number 49 to 96 were the control group. The control group was treated with flunarizine, and the observation group was treated with Tuling Wendan Decoction combined with flunarizine. Comparing the efficacy, incidence of adverse reactions, the incidence of headache, cerebral blood flow rate [basal artery (BA), vertebral artery (VA), middle cerebral artery (MCA)], vascular endothelial function (serum COX-2, ET-1, NO levels), neurological function [5-hydroxytryptamine (5-HT), brain-derived neurotrophic factor (BDNF), calcitonin gene-related peptide (CGRP)] before treatment, 4 weeks and 8 weeks after treatment between the two groups. The results for efficacy showed that after 8 weeks of treatment, the total effective rate of the observation group (93.75%) was higher than that of the control group (77.08%, P<0.05). In regards to the situation of headache attack, the number of headache attacks, duration, pain degree and accompanying symptom scores of the observation group after 4 weeks and 8 weeks of treatment were lower than those of the control group (P<0.05). Results of cerebral blood flow velocity showed that the blood flow velocity of BA, VA, MCA in the observation group was lower than that in the control group after 4 and 8 weeks of treatment (P<0.05). Vascular endothelial function results indicated that the serum COX-2 and ET-1 levels of the observation group were lower than those of the control group after 4 weeks and 8 weeks of treatment, and the serum NO levels were higher than that of the control group (P<0.05). The serum BDNF and CGRP levels of the observation group were lower than those of the control group after 4 weeks and 8 weeks of treatment, and the serum 5-HT levels were higher than the control group (P<0.05). The incidence of adverse reactions between the two groups was not statistically significant (P>0.05). It was concluded that Tuling Wendan Decoction combined with

Topics: Adult; Cerebrovascular Circulation; Cyclooxygenase 2; Drugs, Chinese Herbal; Endothelin-1; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Nitric Oxide; Young Adult

Recent studies indicated that migraine is associated with specific vascular risk profile. However, the functional and structural vascular abnormalities in migraine are rarely addressed. We evaluated the vascular risk factors, endothelial function, and carotid artery (CA)-intima-media thickness (IMT), segregators of preclinical atherosclerosis, in migraineurs. This preliminary study included 63 adults with headache (migraine with aura [n=14], migraine without aura [n=24], transformed migraine [n=6], and tension headache [n=19]) and 35 matched healthy subjects. The following vascular risks were assessed: body mass index (BMI), systolic blood pressure (SBP) and diastolic blood pressures (DBP), serum levels of C-reactive protein, fasting glucose, fasting insulin, total cholesterol, and triglycerides. Plasma endothelin (ET)-1, a vasoactive peptide produced by vascular smooth muscle cells and marker for endothelial injury and atherosclerosis, was measured. Endothelial-dependent vasoreactivity was assessed using brachial artery flow-mediated dilatation (FMD) in response to hyperemia. CA-IMT, structural marker of early atherosclerosis, was measured. Compared with control subjects, SBP, DBP, glucose, insulin, ET-1, and CA-IMT were elevated with migraine. FMD% was inversely correlated with SBP (P < .001), DBP (P < .01), glucose (P < .001), and insulin levels (P < .01). CA-IMT was correlated with BMI (P < .05), SBP (P < .01), total cholesterol (P < .01), triglycerides (P < .001), glucose (P < .001), insulin (P < .01), and FMD% (P < .05). In multivariate analysis, ET-1 was correlated with duration of illness, SBP, DBP, glucose, insulin, IMT, and FMD%. We conclude that endothelial injury, impaired endothelial vasoreactivity, and increased CA-IMT occur with migraine and are associated with vascular risk factors that strongly suggest that migraine could be a risk for atherosclerosis.

Topics: Adult; Biomarkers; Blood Glucose; Blood Pressure; Body Mass Index; C-Reactive Protein; Carotid Arteries; Carotid Artery Diseases; Case-Control Studies; Cholesterol; Comorbidity; Diabetes Complications; Endothelial Cells; Endothelin-1; Female; Humans; Hypertension; Male; Migraine Disorders; Multivariate Analysis; Risk Factors; Triglycerides; Tunica Intima; Vasoconstriction

Migraine with aura is a risk factor for ischemic stroke, but the mechanism by which these disorders are associated remains unclear. Both disorders exhibit familial clustering, which may imply a genetic influence on migraine and stroke risk. Genes encoding for endothelial function are promising candidate genes for migraine and stroke susceptibility because of the importance of endothelial function in regulating vascular tone and cerebral blood flow.. Using data from the Stroke Prevention in Young Women study, a population-based case-control study including 297 women aged 15 to 49 years with ischemic stroke and 422 women without stroke, we evaluated whether polymorphisms in genes regulating endothelial function, including endothelin-1 (EDN), endothelin receptor type B (EDNRB), and nitric oxide synthase-3 (NOS3), confer susceptibility to migraine and stroke.. EDN SNP rs1800542 and rs10478723 were associated with increased stroke susceptibility in whites (OR, 2.1; 95% CI, 1.1-4.2 and OR, 2.2; 95% CI, 1.1-4.4; P=0.02 and 0.02, respectively), as were EDNRB SNP rs4885493 and rs10507875, (OR, 1.7; 95% CI, 1.1-2.7 and OR, 2.4; 95% CI, 1.4-4.3; P=0.01 and 0.002, respectively). Only 1 of the tested SNP (NOS3 rs3918166) was associated with both migraine and stroke.. In our study population, variants in EDN and EDNRB were associated with stroke susceptibility in white but not in black women. We found no evidence that these genes mediate the association between migraine and stroke.

Topics: Adolescent; Adult; Black People; Case-Control Studies; Cohort Studies; DNA Mutational Analysis; Endothelin-1; Endothelium, Vascular; Female; Genetic Predisposition to Disease; Genetic Testing; Genotype; Humans; Middle Aged; Migraine Disorders; Mutation; Nitric Oxide Synthase Type III; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Receptor, Endothelin B; Stroke; White People; Young Adult

There is evidence to suggest that vasospasm and vascular dysregulation play a role in the etiology of glaucoma. This effect may be particularly relevant in patients with glaucoma who have a history of migraine or vasospastic tendencies. This study was conducted to investigate the role of genes with products that regulate blood flow to ocular tissues. The candidate genes were the two isoforms of nitric oxide synthase (NOS), NOS3 and -2A, and endothelin (ET)-l. The frequency of the T786C mutation in NOS3 was also examined.. DNA was obtained from 58 patients with primary open-angle glaucoma (POAG), 76 with normal tension glaucoma (NTG), and 38 control subjects. Polymerase chain reactions (PCR) were used to compare the frequency of the alleles between the subjects with glaucoma and the control subjects and the subjects with glaucoma with vasospasm or migraine. The PCR product was sequenced to identify the frequency of the T786C mutation.. The distribution of the NOS3 repeat alleles in subjects with glaucoma and control subjects just failed to reach statistical significance (P = 0.06). The distribution in subjects with NTG or POAG did not differ significantly. A significant difference was found (P < 0.001) in the distribution of allele frequencies of the NOS3 marker in subjects who had glaucoma with migraine versus control subjects. There were no differences in the distribution of the NOS2A or ET-1 markers between the subjects with glaucoma and the control subjects.. This study provides evidence of an association between the NOS3 gene and subjects with glaucoma who have a history of migraine. Unlike in other studies, no evidence was found of an association between ET-1 and glaucoma.

Topics: Aged; Endothelin-1; Female; Gene Frequency; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Migraine Disorders; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Polymerase Chain Reaction

Previous studies have described an association between migraine and endothelin, a potent vasoconstrictor.. To test the association between migraine and gene polymorphisms of the endothelin system.. A population-based study of elderly individuals (n = 1,188) in Nantes (western France) was conducted. Lifetime migraine was defined according to the International Headache Society criteria, after an interview with a headache specialist. Five polymorphisms in genes encoding endothelin 1, endothelin type A (ET(A)), and type B receptors were determined in more than 90% of the sample. RESULTS Migraine was diagnosed in 140 participants (11.9%). The ETA (-231 A/G) polymorphism was the only polymorphism significantly associated with migraine. There was a trend of decreasing prevalence of migraine with number of copies of the G allele (AA genotype: 15.7% of participants with migraine, AG: 9.7%, GG: 2.9%; p < 0.001). Carrying the G allele was associated with a sex- and age-adjusted odds ratio of 0.50 (95% CI, 0.34 to 0.74). The association was observed in both sexes and was stronger in participants with a family history of severe headaches than in those without.. A variant of the ET(A) receptor gene modulates the risk for migraine. These results offer new insights into the pathophysiology of the vascular component of migraine.

Topics: Age Factors; Aged; Alleles; Cerebrovascular Circulation; DNA Mutational Analysis; Endothelin-1; Female; Genotype; Humans; Longitudinal Studies; Male; Migraine Disorders; Nitric Oxide; Polymorphism, Genetic; Prevalence; Receptor, Endothelin A; Receptors, Endothelin; Risk Factors; Sex Factors; Vasoconstriction

Vasopressin levels in plasma rise during migraine attacks. Vasopressin also induces endothelin-1 synthesis in endothelial cells, suggesting a role as a mediator of elevated plasma endothelin-1 in migraine. To explore a possible relationship between endothelin-1 and vasopressin in migraine, plasma concentrations of both peptides were monitored simultaneously throughout an attack and during two migraine-free intervals (control) in 20 patients. Endothelin-1 was elevated 6 h after the onset of an attack (3.3 +/- 0.3 pg/ml vs 2.7 +/- 0.2 pg/ml during migraine-free intervals; p = 0.12) whereas vasopressin was increased over control levels (2.8 +/- 0.3 pg/ml) by 3 h (3.6 +/- 0.4 pg/ml; p < 0.05) and remained elevated at 6 h (3.9 +/- 0.5 pg/ml; p < 0.01). These data suggest that vasopressin may act as a peripheral mediator of increased plasma endothelin-1 in migraine.

Topics: Adult; Endothelin-1; Female; Humans; Male; Middle Aged; Migraine Disorders; Monitoring, Physiologic; Osmolar Concentration; Vasopressins