Proof of Concept: Endogenous Antiangiogenic Factors Predict the Occurrence of Symptomatic Vasospasm Post Subarachnoid Hemorrhage
- First Online:
- 153 Downloads
The pathogenesis of vasospasm (VS) post aneurysmal subarachnoid hemorrhage (SAH) is multifactorial and not completely understood. The authors hypothesize that circulating antiangiogenic factors play an important role in brain injury post SAH and that elevated levels predict the occurrence of symptomatic vasospasm.
In this study the authors measured the serum and cerebrospinal fluid (CSF) levels of soluble endoglin (sEng) and soluble fms-like tyrosine kinase 1 (sFlt1) in controls and SAH patients within 48 h of the bleed. Patients were prospectively followed and subcategorized into those with (sVS) and without symptomatic vasospasm (no-sVS).
Compared to healthy controls, SAH patients had higher CSF levels of sEng (0.037 vs. 0.251 ng/ml; P = 0.02) and sFlt1 (0.068 vs. 0.679 ng/ml; P = 0.001). In the subgroup analysis, sVS patients had higher CSF levels of sEng and sFlt1 than no-sVS patients (sEng: 0.380 vs. 0.159 ng/ml, P = 0.02; sFlt1: 1.277 vs. 0.343 ng/ml, P = 0.01). The serum levels of sEng and sFlt1 were not statistically different among the different groups.
Based on these results the authors conclude that elevated CSF levels of sFlt1 and sEng herald the occurrence of symptomatic VS post SAH.
KeywordsSubarachnoid hemorrhage Antiangiogenic factors Vasospasm
- 7.Zhu Y, Culmsee C, Klumpp S, Krieglstein J. Neuroprotection by transforming growth factor-beta1 involves activation of nuclear factor-kappaB through phosphatidylinositol-3-OH kinase/Akt and mitogen-activated protein kinase-extracellular-signal regulated kinase1, 2 signaling pathways. Neuroscience. 2004;123:897–906.PubMedCrossRefGoogle Scholar
- 16.Quantakine. Human Endoglin/CD 15 Immunoassay. R&D Systems, Inc. 2009. http://www.rndsystems.com/pdf/dndg00.pdf. Accessed 04 July 2011.
- 17.Quantakine. Human Soluble VEGF R1/FLT-1 Immunoasssay. R&D Systems, Inc. 2009. http://www.rndsystems.com/pdf/DVR100B.pdf. Accessed 04 July 2011.
- 19.Ata KA, Lennmyr F, Funa K, Olsson Y, Terent A. Expression of transforming growth factor-beta1,2,3 isoforms and type I and II receptors in acute focal cerebral ischemia: an immunohistochemical study in rat after transient and permanent occlusion of middle cerebral artery. Acta Neuropathol. 1999;97:447–55.PubMedCrossRefGoogle Scholar
- 29.Venkatesha S, Toporsian M, Lam C, Hanai J, Mammoto T, Kim YM, Bdolah Y, Lim KH, Yuan HT, Libermann TA, Stillman IE, Roberts D, D’Amore PA, Epstein FH, Sellke FW, Romero R, Sukhatme VP, Letarte M, Karumanchi SA. Soluble endoglin contributes to the pathogenesis of preeclampsia. Nat Med. 2006;12:642–9.PubMedCrossRefGoogle Scholar
- 31.Bederson JB, Connolly ES Jr, Batjer HH, Dacey RG, Dion JE, Diringer MN, Duldner JE Jr, Harbaugh RE, Patel AB, Rosenwasser RH. American Heart Association Guidelines for the management of aneurysmal subarachnoid hemorrhage: a statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke. 2009;40:994–1025.PubMedCrossRefGoogle Scholar