Altered vascular functions in migraine patients: Focusing on clinical profiles, neuroimaging, central hemodynamic parameters, and circulating biomarkers
| Autor: | Chun-Yu Cheng, 鄭淳予 |
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| Rok vydání: | 2018 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 106 Background: The impact of migraine on patient health is complicated by cerebro- and cardio-vascular risk factors and comorbidity. The role of central pulsatile hemodynamics in the pathogenesis of white matter hyperintensities (WMHs) in migraine patients has not been clarified. MicroRNAs (miRs) have emerged as important regulators of vascular endothelial functions. Yet, whether levels of miRs associated with endothelial dysfunction are altered in migraine patients remains unknown. Aims: Our study aims were (1) to shed light on possible mechanism of increased risk of vascular events and WMHs formation in migraine patients, (2) to investigate whether potential vascular parameters correlate with WMHs presence or clinical profiles in migraine patients, and (3) to explore the relationship between circulating endothelial-specific miRs and migraine. Methods: Patients with migraine without overt vascular risk factors and demographically-matched healthy controls were recruited prospectively. Cerebral WMHs volume was determined by T1-weighted magnetic resonance imaging with CUBE-fluid-attenuated-inversion-recovery sequences. Central systolic blood pressure (cSBP), carotid-femoral pulse wave velocity (cf-PWV), and carotid augmentation index (AI) were measured by applanation tonometry. Carotid pulsatility index (CPI) was derived from Doppler ultrasound carotid artery flow analysis. The levels of four endothelial-specific miRs (miR-155, miR-126, miR-21, and Let-7g) were quantified and expressed in terms of fold changes (2-ΔΔct) relative to mean levels in the control group. Associations of miRs levels with headache features and syncope comorbidity were explored. Results: Compared to the controls, the migraine patients had a higher WMHs frequency [odds ratio (OR), 2.75; P = 0.04) and greater mean WMHs volume (0.174 vs. 0.049, cm3, P = 0.04). Multivariable regression analysis showed that WMHs volume in migraine patients was positively associated with cSBP (P = 0.04) and cf-PWV (P < 0.001), but negatively associated with CPI (P = 0.04) after controlling for potential confounding factors. The interaction effects observed indicated that the influence of cf-PWV (P = 0.004) and cSBP (P = 0.03) on WMHs formation was greater for the lower-CPI subgroup of migraine patients. Compared to controls, migraine patients had upregulated expression of miR-155 (6.17-fold, P = 0.018), miR-126 (6.17-fold, P = 0.013), and let-7g (7.37-fold, P = 0.005). Levels of miR-155 (r = 0.375, P = 0.041) and miR-126 (r = 0.375, P = 0.041) were associated with the syncope frequency in the past year in migraine patients. Conclusions: Increased aortic stiffness or CBP in the presence of low intracranial artery resistance may predispose migraine patients to WMHs formation; this suggested pathophysiology differs from that observed in non-migraine elderly subjects. Circulating levels of endothelial-specific miRs were elevated and associated with syncope comorbidity in migraine patients. Our findings may shed light on understanding the mechanism mediating altered vascular dysfunctions in migraine and suggest that quantification of targeted vascular parameters and miRs, could be used for stratification of vascular risks in migraine patients. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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