Soluble Endoglin and Transforming Growth Factor-β1 and the Development of Vasospasm after Spontaneous Subarachnoid Hemorrhage: A Pilot StudyDietmann A. · Lackner P. · Fischer M. · Broessner G. · Pfausler B. · Helbok R. · Schmutzhard E. · Beer R.
Department of Neurology, Innsbruck Medical University, Innsbruck, Austria
Do you have an account?
- Rent for 48h to view
- Buy Cloud Access for unlimited viewing via different devices
- Synchronizing in the ReadCube Cloud
- Printing and saving restrictions apply
Rental: USD 8.50
Cloud: USD 20.00
Article / Publication Details
Background:Cerebral vasospasm (CVS) and cerebral infarction due to vasospasm (CIV) are major complications after spontaneous subarachnoid hemorrhage (SAH). Alteration of vasomotor tone has been postulated as an important factor in the pathogenesis of CVS. Members of the transforming growth factor-β (TGF-β) family and their receptors have been implicated in the regulation of vascular tone. Methods:Serum levels of soluble endoglin (sEng) and plasma levels of TGF-β1 of 20 consecutive SAH patients were analyzed within 15 days after SAH using ELISA and correlated with CVS, CIV and outcome. Twenty voluntary age- and sex-matched blood donors served as healthy controls (HCs). Results:SAH patients showed significantly lower sEng serum levels and higher TGF-β1 plasma levels compared to HCs. Patients who developed Doppler sonographic CVS (dCVS) had significantly higher TGF-β1 levels. Patients with CIV and patients with hydrocephalus showed significantly lower sEng levels. On day 3, pSAH sEng levels below 3.88 ng/ml or TGF-β1 levels higher than 7.2 ng/ml had a predictive value for the development of CIV. Low mean sEng levels over the study period were highly predictive of poor long-term functional outcome (modified Rankin Scale ≧2) at 6 months after SAH. Conclusions:Concentrations of the vasoactive factors sEng in serum and TGF-β1 in plasma are significantly altered in SAH patients compared to HCs. The results of this pilot study indicate that sEng could represent a novel prognostic biomarker for the onset of secondary complications and long-term functional outcome after SAH.
© 2011 S. Karger AG, Basel
- Solenski NJ, Haley EC Jr, Kassell NF, Kongable G, Germanson T, Truskowski L, et al: Medical complications of aneurysmal subarachnoid hemorrhage: a report of the multicenter, cooperative aneurysm study. Participants of the Multicenter Cooperative Aneurysm Study. Crit Care Med 1995;23:1007–1017.
- Kolias AG, Sen J, Belli A: Pathogenesis of cerebral vasospasm following aneurysmal subarachnoid hemorrhage: putative mechanisms and novel approaches. J Neurosci Res 2009;87:1–11.
- Lopez-Novoa JM, Bernabeu C: The physiological role of endoglin in the cardiovascular system. Am J Physiol Heart Circ Physiol 2010;299:H959–H974.
- Venkatesha S, Toporsian M, Lam C, Hanai J, Mammoto T, Kim YM, et al: Soluble endoglin contributes to the pathogenesis of preeclampsia. Nat Med 2006;12:642–649.
- Iwasa K, Bernanke DH, Smith RR, Yamamoto Y: Nonmuscle arterial constriction after subarachnoid hemorrhage: role of growth factors derived from platelets. Neurosurgery 1993;32:619–624.
- Cheifetz S, Bellon T, Cales C, Vera S, Bernabeu C, Massague J, et al: Endoglin is a component of the transforming growth factor-β receptor system in human endothelial cells. J Biol Chem 1992;267:19027–19030.
- Lebrin F, Deckers M, Bertolino P, ten Dijke P: TGF-β receptor function in the endothelium. Cardiovasc Res 2005;65:599–608.
- Lackner P, Dietmann A, Beer R, Fischer M, Broessner G, Helbok R, et al: Cellular microparticles as a marker for cerebral vasospasm in spontaneous subarachnoid hemorrhage. Stroke 2010;41:2353–2357.
- Sloan MA, Haley EC Jr, Kassell NF, Henry ML, Stewart SR, Beskin RR, et al: Sensitivity and specificity of transcranial Doppler ultrasonography in the diagnosis of vasospasm following subarachnoid hemorrhage. Neurology 1989;39:1514–1518.
- Sloan MA, Alexandrov AV, Tegeler CH, Spencer MP, Caplan LR, Feldmann E, et al: Assessment: transcranial Doppler ultrasonography: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2004;62:1468–1481.
- Broessner G, Lackner P, Hoefer C, Beer R, Helbok R, Grabmer C, et al: Influence of red blood cell transfusion on mortality and long-term functional outcome in 292 patients with spontaneous subarachnoid hemorrhage. Crit Care Med 2009;37:1886–1892.
- Toporsian M, Gros R, Kabir MG, Vera S, Govindaraju K, Eidelman DH, et al: A role for endoglin in coupling eNOS activity and regulating vascular tone revealed in hereditary hemorrhagic telangiectasia. Circ Res 2005;96:684–692.
- Jerkic M, Rodriguez-Barbero A, Prieto M, Toporsian M, Pericacho M, Rivas-Elena JV, et al: Reduced angiogenic responses in adult Endoglin heterozygous mice. Cardiovasc Res 2006;69:845–854.
- Hanggi D, Steiger HJ: Nitric oxide in subarachnoid haemorrhage and its therapeutic implications. Acta Neurochir (Wien) 2006;148:605–613.
- Freyssinet JM: Cellular microparticles: what are they bad or good for? J Thromb Haemost 2003;1:1655–1662.
- Douglas MR, Daniel M, Lagord C, Akinwunmi J, Jackowski A, Cooper C, et al: High CSF transforming growth factor β levels after subarachnoid haemorrhage: association with chronic communicating hydrocephalus. J Neurol Neurosurg Psychiatry 2009;80:545–550.
- Flood C, Akinwunmi J, Lagord C, Daniel M, Berry M, Jackowski A, et al: Transforming growth factor-β1 in the cerebrospinal fluid of patients with subarachnoid hemorrhage: titers derived from exogenous and endogenous sources. J Cereb Blood Flow Metab 2001;21:157–162.
- Kitazawa K, Tada T: Elevation of transforming growth factor-β1 level in cerebrospinal fluid of patients with communicating hydrocephalus after subarachnoid hemorrhage. Stroke 1994;25:1400–1404.
- Cruz-Gonzalez I, Pabon P, Rodriguez-Barbero A, Martin-Moreiras J, Pericacho M, Sanchez PL, et al: Identification of serum endoglin as a novel prognostic marker after acute myocardial infarction. J Cell Mol Med 2008;12:955–961.
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.