Yliopiston etusivulle Suomeksi På svenska In English Helsingin yliopisto

On the genetics of intracranial aneurysm and on growth factor induced angiogenesis in the murine brain

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dc.contributor Helsingin yliopisto, lääketieteellinen tiedekunta, kliininen laitos fi
dc.contributor Helsingfors universitet, medicinska fakulteten, institutionen för klinisk medicin sv
dc.contributor University of Helsinki, Faculty of Medicine, Institute of Clinical Medicine, Neurosurgery en
dc.contributor The Neurosurgery Research Group, National Institute for Health and Welfare; Institute for Molecular Medicine Finland, Molecular/Cancer Biology Laboratory, Haartman Institute and Biomedicum Helsinki, Faculty of Medicine, University of Helsinki, Finland; The Yale Neurogenetics Program, Yale School of Medicine, New Haven, CT, USA en
dc.contributor.author Gaal, Emilia fi
dc.date.accessioned 2012-11-15T13:48:28Z
dc.date.available 2012-11-20 fi
dc.date.available 2012-11-15T13:48:28Z
dc.date.issued 2012-11-30 fi
dc.identifier.uri URN:ISBN:978-952-10-8369-3 fi
dc.identifier.uri http://hdl.handle.net/10138/37553
dc.description.abstract Cerebrovascular diseases continue to challenge us by robbing lives and leaving many disabled still in their prime working age. Some cerebrovascular diseases are more acute in nature, and some erode the quality of life over a long period of time. A life-threatening form of acute cerebrovascular disease is brought on by the rupture of an intracranial aneurysm (IA). Most IAs are berry-shaped pouches at the forking site of cerebral arteries. Since according to autopsy results, 2-5% of the population harbours IA, it is a common disease. Most IA go unnoticed during one s lifetime, however, often the first symptom they give is their deadly rupture. Likely, both environmental factors and a compound genetic susceptibility, contribute to the risk of IA, making it a complex disease. The aim of studies I-III was to test whether in humans common genetic variants contribute to the susceptibility to IA (I,II), and to seek genetic evidence for their pathomechanism (III). In multinational genome-wide association studies (I,II) we identified 5 loci with strong statistical evidence of association with IA, and a further 14 loci with suggestive evidence. Further, we found that suggestive IA risk locus at 5q26 is strongly associated with high systolic blood pressure in over 210 000 individuals of European descent, highlighting the connection between hypertension and IA (III). To gain further insight into cerebral vasculopathies and to facilitate the development of novel therapies, in study (IV) we turned our attention to vascular growth factor induced angiogenesis in a model organism. We tested by viral gene transfer the known vascular growth factors in the murine central nervous system and characterised extensively the angiogenesis upon treatment. The aim of the study was to identify the best candidate vascular growth factor(s) for therapeutic brain angiogenesis. We identified placenta growth factor as the most safe and efficient candidate for therapeutic revascularisation of the central nervous system. We envision a placenta growth factor enhanced multiple bur hole indirect extracranial-intracranial bypass as a novel therapeutic approach in the brain, possibly aiding the treatment of diseases such as chronic cerebral hypoperfusion, complex IAs and stroke. en
dc.description.abstract Cerebrovascular diseases continue to challenge us by robbing lives and leaving many disabled still in their prime working age. Some cerebrovascular diseases are more acute in nature, and some erode the quality of life over a long period of time. A life-threatening form of acute cerebrovascular disease is brought on by the rupture of an intracranial aneurysm (IA). Most IAs are berry-shaped pouches at the forking site of cerebral arteries. Since according to autopsy results, 2-5% of the population harbours IA, it is a common disease. Most IA go unnoticed during one s lifetime, however, often the first symptom they give is their deadly rupture. Likely, both environmental factors and a compound genetic susceptibility, contribute to the risk of IA, making it a complex disease. The aim of studies I-III was to test whether in humans common genetic variants contribute to the susceptibility to IA (I,II), and to seek genetic evidence for their pathomechanism (III). In multinational genome-wide association studies (I,II) we identified 5 loci with strong statistical evidence of association with IA, and a further 14 loci with suggestive evidence. Further, we found that suggestive IA risk locus at 5q26 is strongly associated with high systolic blood pressure in over 210 000 individuals of European descent, highlighting the connection between hypertension and IA (III). To gain further insight into cerebral vasculopathies and to facilitate the development of novel therapies, in study (IV) we turned our attention to vascular growth factor induced angiogenesis in a model organism. We tested by viral gene transfer the known vascular growth factors in the murine central nervous system and characterised extensively the angiogenesis upon treatment. The aim of the study was to identify the best candidate vascular growth factor(s) for therapeutic brain angiogenesis. We identified placenta growth factor as the most safe and efficient candidate for therapeutic revascularisation of the central nervous system. We envision a placenta growth factor enhanced multiple bur hole indirect extracranial-intracranial bypass as a novel therapeutic approach in the brain, possibly aiding the treatment of diseases such as chronic cerebral hypoperfusion, complex IAs and stroke. fi
dc.format.mimetype application/pdf fi
dc.language.iso en fi
dc.publisher Helsingin yliopisto fi
dc.publisher Helsingfors universitet sv
dc.publisher University of Helsinki en
dc.relation.isformatof URN:ISBN:978-952-10-8368-6 fi
dc.relation.isformatof 2012 fi
dc.rights Julkaisu on tekijänoikeussäännösten alainen. Teosta voi lukea ja tulostaa henkilökohtaista käyttöä varten. Käyttö kaupallisiin tarkoituksiin on kielletty. fi
dc.rights This publication is copyrighted. You may download, display and print it for Your own personal use. Commercial use is prohibited. en
dc.rights Publikationen är skyddad av upphovsrätten. Den får läsas och skrivas ut för personligt bruk. Användning i kommersiellt syfte är förbjuden. sv
dc.subject genetiikka, angiogeneesi fi
dc.title On the genetics of intracranial aneurysm and on growth factor induced angiogenesis in the murine brain en
dc.type.ontasot Väitöskirja (artikkeli) fi
dc.type.ontasot Doctoral dissertation (article-based) en
dc.type.ontasot Doktorsavhandling (sammanläggning) sv
dc.ths Niemelä, Mika fi
dc.ths Palotie, Aarno fi
dc.ths Alitalo, Kari fi
dc.opn Langmoen, Iver A. fi
dc.type.dcmitype Text fi

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