Publications (15)42.35 Total impact
-
Article: Oxidative Stress is Associated With Cell Death, Wall Degradation, and Increased Risk of Rupture of the Intracranial Aneurysm Wall.
[show abstract] [hide abstract]
ABSTRACT: BACKGROUND:: The cause for rupture of intracranial aneurysms (IA) is not well understood. We previously demonstrated that loss of cells from the IA wall is associated with wall degeneration and rupture. OBJECTIVE:: To investigate the mechanisms mediating cell death in the IA wall. METHODS:: Snap-frozen tissue samples from aneurysm fundi were studied with TUNEL staining and immunostaining (14 unruptured and 20 ruptured), as well as with western blot (12 unruptured and 12 ruptured). RESULTS:: Ruptured IA walls had more TUNEL+ cells than unruptured walls (P < .001). Few cells positive for cleaved caspase-3 were detected. Cleaved caspase-9 (intrinsic activation of apoptosis) was significantly increased in ruptured IA walls, whereas cleaved caspase-8 (extrinsic activation of apoptosis) was not detected. Increased expression of hemeoxygenase-1, a marker for oxidative stress, was associated with IA wall degeneration and rupture. CONCLUSION:: Our results show that programmed cell death is activated in the IA wall via the intrinsic pathway. High oxidative stress in the IA wall is probably a significant cause of the intrinsic activation of cell death.Neurosurgery 10/2012; · 2.79 Impact Factor -
Article: Saccular intracranial aneurysm: pathology and mechanisms.
[show abstract] [hide abstract]
ABSTRACT: Saccular intracranial aneurysms (sIA) are pouch-like pathological dilatations of intracranial arteries that develop when the cerebral artery wall becomes too weak to resist hemodynamic pressure and distends. Some sIAs remain stable over time, but in others mural cells die, the matrix degenerates, and eventually the wall ruptures, causing life-threatening hemorrhage. The wall of unruptured sIAs is characterized by myointimal hyperplasia and organizing thrombus, whereas that of ruptured sIAs is characterized by a decellularized, degenerated matrix and a poorly organized luminal thrombus. Cell-mediated and humoral inflammatory reaction is seen in both, but inflammation is clearly associated with degenerated and ruptured walls. Inflammation, however, seems to be a reaction to the ongoing degenerative processes, rather than the cause. Current data suggest that the loss of mural cells and wall degeneration are related to impaired endothelial function and high oxidative stress, caused in part by luminal thrombosis. The aberrant flow conditions caused by sIA geometry are the likely cause of the endothelial dysfunction, which results in accumulation of cytotoxic and pro-inflammatory substances into the sIA wall, as well as thrombus formation. This may start the processes that eventually can lead to the decellularized and degenerated sIA wall that is prone to rupture.Acta Neuropathologica 01/2012; 123(6):773-86. · 9.32 Impact Factor -
Article: Delayed vasospasm in aneurysmal subarachnoid hemorrhage.
World Neurosurgery 01/2012; 77(1):39-41. · 0.68 Impact Factor -
Article: Upregulated signaling pathways in ruptured human saccular intracranial aneurysm wall: an emerging regulative role of Toll-like receptor signaling and nuclear factor-κB, hypoxia-inducible factor-1A, and ETS transcription factors.
[show abstract] [hide abstract]
ABSTRACT: Aneurysmal subarachnoid hemorrhage, almost always from saccular intracranial aneurysm (sIA), is a devastating form of stroke that affects the working-age population. Cellular and molecular mechanisms predisposing to the rupture of the sIA wall are largely unknown. This knowledge would facilitate the design of novel diagnostic tools and therapies for the sIA disease. To investigate gene expression patterns distinguishing ruptured and unruptured sIA. We compared the whole-genome expression profile of 11 ruptured sIA wall samples with that of 8 unruptured ones using oligonucleotide microarrays. Signaling pathways enriched in the ruptured sIA walls were identified with bioinformatic analyses. Their transcriptional control was predicted in silico by seeking the enrichment of conserved transcription factor binding sites in the promoter regions of differentially expressed genes. Overall, 686 genes were significantly upregulated and 740 were downregulated in the ruptured sIA walls. Significantly upregulated biological processes included response to turbulent blood flow, chemotaxis, leukocyte migration, oxidative stress, vascular remodeling; and extracellular matrix degradation. Toll-like receptor signaling and nuclear factor-κB, hypoxia-inducible factor-1A, and ETS transcription factor binding sites were significantly enriched among the upregulated genes. We identified pathways and candidate genes associated with the rupture of human sIA wall. Our results may provide clues to the molecular mechanism in sIA wall rupture and insight for novel therapeutic strategies to prevent rupture.Neurosurgery 02/2011; 68(6):1667-75; discussion 1675-6. · 2.79 Impact Factor -
Article: [Why does the cerebral artery aneurysm rupture?].
[show abstract] [hide abstract]
ABSTRACT: Subarachnoid hemorrhage caused by rupture of a cerebral artery aneurysm leads to the death of nearly 500 people in Finland per year. The mechanism of aneurysmal rupture remains unknown at present. It is, however, known that a chronic inflammatory reaction is going on in the aneurysmal wall, being associated with the degeneration of the aneurysmal wall and susceptibility of the aneurysm to bleeding. Unambiguous screening or identification of bleeding-prone aneurysms cannot be performed. The diagnostics and treatment of bleeding-prone aneurysms can possibly be improved in the future by applying imaging of the chronic inflammation and drug therapy.Duodecim; lääketieteellinen aikakauskirja 01/2011; 127(3):244-52. -
Article: Isolation, culture, and characterization of smooth muscle cells from human intracranial aneurysms.
[show abstract] [hide abstract]
ABSTRACT: Smooth muscle cells (SMCs) play a critical role in the vascular wall and also participate in vascular repair mechanisms. Dysfunction of SMCs may also contribute to the formation of intracranial aneurysms (IAs) causing subarachnoid hemorrhage. Our aim was to investigate the possibility of using cultured SMCs as an in vitro model for the study of aneurysmal SMCs. IA tissue was obtained during microsurgical ligation of IAs. By using the explant method, cell cultures were established from the aneurysmal tissue. The phenotype of cultured cells from passage to passage was studied using immunoperoxidase staining and Western blotting. Eight cell lines could be established from 29 IA samples. Four lines showing most rigorous growth were investigated more thoroughly. Abundant expression of SMC markers, α-smooth muscle cell actin and calponin, as well as of prolyl-4-hydroxylases, a key enzyme family in the synthesis of collagens, was observed in all of them. Aneurysmal SMCs in culture maintained their phenotype and SMC characteristics through the early passages of growth. This is the first documented successful culture of SMCs from human IAs. An access to living human cells of aneurysmal origin gives us a new tool in our research of the formation, growth, and rupture of IAs.Acta Neurochirurgica 10/2010; 153(2):311-8. · 1.52 Impact Factor -
Article: Lack of complement inhibitors in the outer intracranial artery aneurysm wall associates with complement terminal pathway activation.
[show abstract] [hide abstract]
ABSTRACT: Inflammation and activation of the complement system predispose to intracranial artery aneurysm (IA) rupture. Because disturbances in complement regulation may lead to increased susceptibility to complement activation and inflammation, we looked for evidence for dysregulation of the complement system in 26 unruptured and 26 ruptured IAs resected intraoperatively. Immunohistochemical and immunofluorescence results of parallel IA sections showed that deposition of the complement activation end-product C5b-9 was lacking from the luminal part of the IA wall that contained complement inhibitors factor H, C4b binding protein, and protectin as well as glycosaminoglycans. In contrast, the outer, less cellular part of the IA wall lacked protectin and had enabled full complement activation and C5b-9 formation. Decay accelerating factor and membrane cofactor protein had less evident roles in complement regulation. The Factor H Y402H variant, studied in 97 IA patients, was seen as often in aneurysm patients with or without aneurysm rupture as in the control population. The regulatory capacity of the complement system thus appears disturbed in the outer part of the IA wall, allowing full proinflammatory complement activation to occur before aneurysm rupture. Insufficient complement control might be due to matrix remodeling and cell loss by mechanical hemodynamics and/or inflammatory stress. Apparently, disturbed complement regulation leads to an increased susceptibility to complement activation, inflammation, and tissue damage in the IA wall.American Journal Of Pathology 10/2010; 177(6):3224-32. · 4.89 Impact Factor -
Article: Inflammatory changes in the aneurysm wall: a review.
[show abstract] [hide abstract]
ABSTRACT: Rupture of a saccular intracranial artery aneurysm (IA) causes subarachnoid hemorrhage, a significant cause of stroke and death. The current treatment options, endovascular coiling and clipping, are invasive and somewhat risky. Since only some IAs rupture, those IAs at risk for rupture should be identified. However, to improve the imaging of rupture-prone IAs and improve IA treatment, IA wall pathobiology requires more thorough knowledge. Chronic inflammation has become understood as an important phenomenon in IA wall pathobiology, featuring inflammatory cell infiltration as well as proliferative and fibrotic remodulatory responses. We review the literature on what is known about inflammation in the IA wall and also review the probable mechanisms of how inflammation would result in the degenerative changes that ultimately lead to IA wall rupture. We also discuss current options in imaging inflammation and how knowledge of inflammation in IA walls may improve IA treatment.Journal of neurointerventional surgery 06/2010; 2(2):120-30. · 0.92 Impact Factor -
Article: Complement system becomes activated by the classical pathway in intracranial aneurysm walls.
[show abstract] [hide abstract]
ABSTRACT: Inflammation and activation of the complement system in the intracranial aneurysm (IA) wall predispose to IA rupture. We have previously shown that increased C5b-9 accumulation correlates with IA rupture and wall degeneration. To elucidate the underlying mechanisms, we investigated initiators and the pathway of complement activation in unruptured and ruptured IAs. Unruptured and ruptured IA wall samples were studied in parallel sections by immunohistochemical and immunofluorescence stainings for the location and relations of classical and alternative pathway complement components (C1q, C3b/iC3b, C3d, C4b/iC4b; n=35 and properdin, n=10), putative complement activators IgG (n=90), IgM, CRP and OxLDL (n=10), and complement activation endproduct C5b-9. Classical pathway components were seen in all IAs, and they were located mostly in the extracellular matrix. The early pathway complement components colocalized with each other, but were present in larger areas than C5b-9. The areas positive for complement component accumulation were significantly broader in ruptured than in unruptured IAs. The potential complement activators IgG, IgM, CRP and OxLDL were found mostly in the extracellular matrix and in partial overlap with C5b-9. Lipids were seen in Oil-Red-O staining in colocalization with C5b-9. Complement becomes activated by the classical pathway in the IA wall. The activation appears to be induced by multiple factors, which, in addition to the traditional activators (immunoglobulins, CRP, OxLDL), could involve vascular pressure-induced tissue damage. Despite wide early pathway activation, the terminal pathway is focused on a distinct lipid-rich layer. The profile of the complement components and the association of C5b-9 with lipids in the extracellular matrix indicate a long-term chronic inflammatory process rather than an acute targeted inflammatory reaction. The observed pattern of complement activation may be the consequence of local stress-induced insufficiency of complement regulation in IA walls.Laboratory Investigation 12/2009; 90(2):168-79. · 3.64 Impact Factor -
Article: Occlusion of neck remnant in experimental rat aneurysms after treatment with platinum- or polyglycolic-polylactic acid-coated coils.
[show abstract] [hide abstract]
ABSTRACT: Neck remnants and aneurysm recurrences are marked limitations of endovascular treatment of cerebral artery aneurysms. We compared the evolution of neck remnants of experimental arterial rat aneurysms after treatment with either platinum- or PGLA-coated coils. We created 20 standard-size aneurysms in the abdominal aortas of male Wistar rats. Aneurysms were embolized with either PGLA-coated coils or platinum coils, with care taken to leave a neck remnant. Neck remnant size and shape was closely monitored to detect progressive enlargement or occlusion. Using a 4.7 T MR scanner, we acquired high-resolution MR images 6 times during the 4-week follow-up. For quantitative measurements, we used a high-resolution 3D-TOF angiography sequence. Results were verified by endoscopy and histology. Aneurysms treated with PGLA coils showed, on average, a 12.9% reduction of neck remnant size (P = .044) and significant disappearance of dog ears, the blood-filled spaces between coils and aneurysm wall. The aneurysms treated with platinum coils lacked these changes. In endoscopy, neointima was found to cover both PGLA and platinum coils but was more often incomplete or translucent in the platinum group. In histology, thrombus organization and inflammatory cell infiltration were higher with PGLA. Use of PGLA-coated coils was followed by a moderate progressive reduction of the neck remnant size and a better angiographic outcome, seen as disappearance of dog ears during follow-up. The rat model proved to be suitable for comparison of different coil types.Surgical Neurology 08/2008; 71(4):458-65; discussion 465. · 1.67 Impact Factor -
Article: Involvement of mitogen-activated protein kinase signaling in growth and rupture of human intracranial aneurysms.
[show abstract] [hide abstract]
ABSTRACT: Mitogen-activated protein kinases (MAPKs) are involved in vascular wall remodeling, but their role in the pathogenesis of intracranial aneurysms (IAs) is poorly known. We investigated the expression and phosphorylation of the 3 major mitogen-activated protein kinases, c-Jun N-terminal kinase (JNK), p38, and extracellular signal-regulated kinase, in unruptured and ruptured human IAs. Tissue samples (n=24, 12 unruptured and 12 ruptured IAs) were obtained during microneurosurgical clipping. The localization of the proteins was studied by immunofluorescent staining, and protein levels and phosphorylation state were studied by Western blotting. The phosphorylation of p54 JNK was increased 1.5-fold in ruptured IAs and the phospho-p54 JNK level and its phosphorylation state directly correlated with IA size. The levels of phosphorylated and total levels of p38 were associated with IA size as well. Extracellular signal-regulated kinase did not associate with IA size or rupture status. Expression of transcription factor c-Jun, a downstream target of JNK, correlated with p54 JNK level and phosphorylation state. Furthermore, the levels of matrix metalloproteinase 9, known to have a role in vessel wall degeneration, correlated with p54 JNK phosphorylation in unruptured IAs and its expression was increased 4.3-fold in ruptured IAs. Our results suggest that JNK activity and expression are involved in IA growth and possibly rupture and p38 expression in IA growth. Thus, pharmacological therapy affecting the stress-activated mitogen-activated protein kinases, JNK and p38, may enhance the repair of the IA wall in the future.Stroke 04/2008; 39(3):886-92. · 5.73 Impact Factor -
Article: Association of fatal aneurysmal subarachnoid hemorrhage with human leukocyte antigens in the Finnish population.
[show abstract] [hide abstract]
ABSTRACT: Human leukocyte antigens (HLA) have been reported to associate with the risk of aneurysmal subarachnoid hemorrhage (SAH) and poor outcome after SAH. Our aim was to identify HLA antigens that associate with the risk of fatal SAH in the Finnish population. Medical records of 600 cadaveric organ donors were reviewed to find organ donors that succumbed to SAH (n = 232) or brain trauma (n = 151). HLA antigen frequencies in these groups were compared with HLA frequencies in a reference population of 10,000 bone marrow donors. Chi-Square test with Bonferroni correction and multiplicative logistic regression models were used and false positive result probabilities (FPRP) were calculated. Alpha-level was 0.01. HLA-A3 associated with fatal SAH (p = 0.0014, OR 1.3 and 95%CI 1.1-1.6) and HLA-DR7 inversely associated with fatal SAH (p = 0.0040, OR 0.3 and 95%CI 0.2-0.6). HLA-A3 but not HLA-DR7 showed also a positive trend in donors with brain trauma. FPRP was below 0.5 for HLA-A3, but clearly above 0.5 for HLA-DR7. HLA-A3 seems to associate with fatal SAH in the Finnish population. Further studies are needed to reveal the pathobiologic mechanisms for how HLA-A3 associates with the risk of fatal SAH in Finns.Human Immunology 03/2007; 68(2):100-5. · 2.84 Impact Factor -
Article: Complement activation associates with saccular cerebral artery aneurysm wall degeneration and rupture.
[show abstract] [hide abstract]
ABSTRACT: Saccular cerebral artery aneurysm (SCAA) wall degeneration and inflammatory cell infiltrations associate with aneurysm rupture and subarachnoid hemorrhage, resulting in a devastating form of stroke. The complement system is the key mediator of inflammation and household processing of injured tissue. We studied how complement activation associates with SCAA wall degeneration and rupture to better understand the pathobiology of SCAA wall rupture. Unruptured (n = 26) and ruptured (n = 32) SCAA fundi resected after microsurgical clipping were studied by immunostaining for complement activation (membrane attack complex [MAC]) and by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling reaction for related cell death. Complement activation was correlated with clinical and other histological parameters. Electromicroscopy and immunoelectron microscopy were used for locating MAC depositions at the ultrastructural level. MAC localized consistently in a decellularized layer in the outer SCAA wall, and was found in all SCAA samples. The percentage of MAC-positive area relative to the total SCAA wall surface area (range, 5-77%) was greater in ruptured (n = 25; median, 39%) than in unruptured SCAAs (n = 18; median, 20%; P = 0.005). It also associated significantly with SCAA wall degeneration (P < 0.001), de-endothelialization(P < 0.001), and CD163+ macrophage (P = 0.023) and T-lymphocyte (P = 0.030) infiltrations. Apoptotic terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling-positive nuclei and MAC were located at the same wall areas in four out of 14 double-stained samples, but no double-positive cells were found. Electromicroscopy and immunoelectron microscopy of an unruptured SCAA showed cell death in the MAC-positive layers in the outer SCAA wall. These data suggests that complement activation and MAC formation are involved in SCAA wall degeneration and rupture.Neurosurgery 11/2006; 59(5):1069-76; discussion 1076-7. · 2.79 Impact Factor -
Article: Contribution of mural and bone marrow-derived neointimal cells to thrombus organization and wall remodeling in a microsurgical murine saccular aneurysm model.
[show abstract] [hide abstract]
ABSTRACT: Endovascular occlusive therapy of human saccular cerebral artery aneurysms may fail because of thrombus recanalization and incomplete neointima formation. Bone marrow-derived progenitor cells may contribute to these processes, but their role in human saccular cerebral artery aneurysms and experimental aneurysm models remains unclear. Experimental saccular aneurysms were constructed from syngeneic thoracic aortas transplanted end-to-side to the abdominal aorta of Wistar rats (n = 14), C57/B6 mice (n = 13), ApoE mice (n = 7), reporter gene expressing ROSA mice (n = 7), and mice with labeled bone marrow (ROSA [n = 12] or green fluorescent protein [n = 3]). Magnetic resonance imaging or angiography was used to monitor patency of the experimental aneurysms. Histology and immunohistochemistry were used to study thrombus organization and neointima formation and X-gal staining and confocal microscopy to study the origin of neointimal cells. Experimental aneurysms developed luminal pads of neointimal hyperplasia or organizing thrombosis that became thicker and occluded partly the lumen at later time points during the first week. Reporter gene mice (ROSA) revealed that 42 to 81% (median, 58%) of neointimal hyperplasia/organizing thrombosis was derived from the experimental aneurysm wall. Bone marrow-derived neointimal cells were found in only 5 of 15 mice (range, 11-73 per section; a median of 22 cells among a total of 2000-6000 wall cells). Thrombus organizing or neointimal cells were mostly derived from the experimental aneurysm wall, with only a minor contribution from the bone marrow. In human saccular cerebral artery aneurysms, the contribution of bone marrow-derived neointimal cells might be more important and should be compared with that found in other experimental models used to develop endovascular therapies.Neurosurgery 06/2006; 58(5):936-44; discussion 936-44. · 2.79 Impact Factor -
Article: Inflammation and Complement Activation in Intracranial Artery Aneurysms
[show abstract] [hide abstract]
ABSTRACT: Intracranial artery aneurysms (IAs) are estimated to be present in 2.3% of the population. A rupture of an IA causes subarachnoid hemorrhage, with up to 50% mortality. The annual low rupture risk of an IA indicates that most IAs never rupture. The current treatment options are invasive and somewhat risky. Thus rupture-prone IAs should be identified and this requires a better understanding of the IA wall pathobiology. Inflammatory cell infiltrations have been found to precede IA rupture, indicating the role of inflammation in IA wall degeneration and rupture. The complement system is a key mediator of inflammation and house-hold processing of injured tissue. This study aimed at identifying the role of complement activation in IA wall degeneration and the complement activators involved and determining how the complement system is regulated in the IA wall. In immunostainings, the end-product of complement activation, the terminal complement complex (TCC), was located mainly in the outer part of the IA wall, in areas that had also sustained loss of cells. In electron microscopy, the area of maximum TCC accumulation contained cellular debris and evidence of both apoptotic and necrotic cell death. Complement activation correlated with IA wall degeneration and rupture, de-endothelialization, and T-cell and CD163-positive macrophage infiltration. The complement system was found to become activated in all IAs by the classical pathway, with recruitment of alternative pathway amplification. Of the potential activators immunoglobulins G and M and oxidatively modified lipids were found in large areas. Lipid accumulation was observed to clearly colocalize with TCC and C-reactive protein. In the luminal parts of the IA wall, complement activation was limited by cellular expression of protectin (CD59) and extracellular matrix-bound inhibitors, C4b binding protein and factor H whereas the outer part of the wall lacked cells expressing protectin as well as matrix-bound factor H. In single nucleotide polymorphism-analysis, age-related macular degeneration-associated factor H Y402H polymorphism did not associate with the presence of IAs or their rupture The data suggest that complement activation and TCC formation are involved in IA wall degeneration and rupture. Complement seems to become activated by more than one specific activator. The association of complement with de-endothelialization and expression of several complement activators indicate a possible role of endothelial dysfunction and/or impaired clearance mechanisms. Impaired complement regulation seems to be associated with increased complement activation in IA walls. These results stress the role of chronic inflammation in IA wall pathobiology and the regulatory role of complement within this process. Imaging inflammation would possibly enhance the diagnostics of rupture-prone IAs, and targeting IA treatment to prevent chronic inflammation might improve IA treatment in the future. Aivovaltimoaneurysma (AA) on aivoverisuonen pullistuma, jonka kantajia arvioidaan olevan Suomessa 100 000. Vuosittain noin 1000 keskimäärin työikäistä henkilöä saa AA:n puhkeamisen aiheuttaman aivoverenvuodon, johon puolet potilaista kuolee ja kolmasosalle jää pysyvä haitta. AA:n puhkeamista ei osata ennustaa eikä siihen johtavia biologisia mekanismeja tunneta tarkasti, vaikkakin tulehdussolujen kertymisen sekä AA-seinämän haurastumisen tiedetään liittyvän puhkeamiseen. Vaikka todennäköisesti osa AA:sta jääkin puhkeamatta, hoitoa ei osata toistaiseksi kohdistaa puhkeamisriskissä oleviin AA:iin eikä AA:n puhkeamista osata estää ilman leikkausta. Tässä väitöskirjatyössä tutkittiin tulehdusta välittävän komplementtijärjestelmän aktivoitumista ja säätelyä AA-kudosnäytteistä ja sekä etsittiin AA:n puhkeamista selittäviä eroja. Komplementtijärjestelmä on ryhmä veressä ja kudoksissa olevia proteiineja, joista osa osallistuu komplementin kaskadimaiseen aktivoitumiseen ja osa estää sitä. Komplementin aktivoituminen välittää inflammaatiota (steriili tulehdus ilman mikrobeja), vaurioittaa terveitä soluja ja houkuttelee tulehdussoluja, joita AA:ssa on aiemmissa tutkimuksissa havaittu. Tulehdus puolestaan voi haurastuttaa AA:n seinämää. Tulosten perusteella komplementtijärjestelmä aktivoituu kaikissa AA:ssa ja aktivaatio tapahtuu ns. klassista tietä eli tiettyjen aktivaattoreiden aiheuttamana. AA:sta löydettiin kertymiä C-reaktiivista (tulehdus)proteiinia, vasta-aineita, hapettuneita LDL-kolesterolipartikkeleita sekä kuolleita soluja, jotka kaikki voivat aktivoida komplementtia. Komplementin täydellinen aktivaatio sijoittui vyöhykemäiselle vähäsoluiselle alueelle AA:n ulkoseinämässä. Alueen laajuus liittyi selkeästi seinämän sisäsolukerroksen (endoteeli) katoamiseen, seinämän haurastumiseen, AA:n puhkeamiseen ja tiettyjen tulehdussolujen kertymiseen. Elektronimikrokopiassa komplementtiaktivaation lopputuotteita löytyi kuolleiksi soluiksi sopivista rakenteista. AA:n sisäseinämässä komplementtiaktivaatiota näytti rajoittavan soluihin ja seinämän tukiaineeseen sitoutuneet inhibiittorit (protektiini sekä C4bp ja faktori H). Näistä protektiinia ei havaittu juurikaan AA:n ulkoseinämässä. Lisäksi tutkittiin faktori H:n geneettistä Y402H-polymorfiaa, jolle ei löydetty yhteyttä AA:iin tai AA:n puhkemiseen. Tulokset osoittavat komplementtiaktivaation edeltävän AA:n puhkeamista ja liittyvän AA-seinämän haurastumiseen ja puhkeamiseen. AA-seinämän komplementtiaktivaatio näyttäisi olevan mahdollisesti seurausta usean aktivaattorin kertymisestä AA-seinämään ja liittyvän vaillinaisen aktivoitumisen eston kautta seinämäsolujen kuolemiseen. Komplementtiaktivaation tarkempi analyysi viittaa AA:n pitkäkestoiseen inflammaatioon, mikä voi olla seurausta normaalien suoja- ja puhdistusmekanismien häiriintymisestä. Saadut tulokset tuovat merkittävää lisätietoa AA-seinämän heikkenemisen mekanismeista ja saattavat ohjata puhkeamisherkkien AA:n tunnistamista ja hoitoa tulevaisuudessa.
Top co-authors
Top Journals
Institutions
-
2006–2012
-
Helsinki University Central Hospital
- Department of Neurosurgery
Helsinki, Province of Southern Finland, Finland
-
