Inflammatory Responses Induced by the Rupture of Intracranial Aneurysms Are Modulated by miRNAs.
Ontology highlight
ABSTRACT:
SUBMITTER: Korostynski M
PROVIDER: S-EPMC7031224 | biostudies-literature | 2020 Feb
REPOSITORIES: biostudies-literature
Publications
Inflammatory Responses Induced by the Rupture of Intracranial Aneurysms Are Modulated by miRNAs.
Korostynski Michal M Morga Rafal R Piechota Marcin M Hoinkis Dzesika D Golda Slawomir S Dziedzic Tomasz T Slowik Agnieszka A Moskala Marek M Pera Joanna J
Molecular neurobiology 20191025 2
Influence of an intracranial aneurysm (IA) rupture on the expression of miRNAs and the potential significance of the resulting changes remains poorly understood. We aimed to characterize the response to the IA rupture through the analysis of miRNAs in peripheral blood cells. Expression of small RNAs was investigated using deep transcriptome sequencing in patients in the acute phase of an IA rupture (first 72 h), in the chronic phase (3-15 months), and controls. A functional analysis and the pote ...[more]
Similar Datasets
Project description:Systemic hypertension has long been considered a risk factor of aneurysmal rupture. However, a causal link between systemic hypertension and the development of aneurysmal rupture has not been established. In this study, using a mouse model of intracranial aneurysm rupture, we examined the roles of systemic hypertension in the development of aneurysmal rupture.Aneurysms were induced by a combination of deoxycorticosterone acetate (DOCA)-salt and a single injection of elastase into the cerebrospinal fluid in mice. Antihypertensive treatment was started 6 days after aneurysm induction. Aneurysmal rupture was detected by neurological symptoms and confirmed by the presence of intracranial aneurysm with subarachnoid hemorrhage. Hydralazine (direct vasodilator) or discontinuation of DOCA-salt treatment was used to assess the roles of systemic hypertension. Captopril (angiotensin-converting enzyme inhibitor) or losartan (angiotensin II type 1 receptor antagonist) was used to assess the roles of the local renin-angiotensin system in the vascular wall.Normalization of blood pressure by hydralazine significantly reduced the incidence of ruptured aneurysms and the rupture rate. There was a dose-dependent relationship between reduction of blood pressure and prevention of aneurysmal rupture. Captopril and losartan were able to reduce rupture rate without affecting systemic hypertension induced by DOCA-salt treatment.Normalization of blood pressure after aneurysm formation prevented aneurysmal rupture in mice. In addition, we found that the inhibition of the local renin-angiotensin system independent from the reduction of blood pressure can prevent aneurysmal rupture.
| S-EPMC3935821 | biostudies-literature
Project description:Background and purposeRupture risk of intracranial aneurysms may depend on hemodynamic characteristics. This has been assessed by comparing hemodynamic data of ruptured and unruptured aneurysms. However, aneurysm geometry may change before, during, or just after rupture; this difference causes potential changes in hemodynamics. We assessed changes in hemodynamics in a series of intracranial aneurysms, by using 3D imaging before and after rupture.Materials and methodsFor 9 aneurysms in 9 patients, we used MRA, CTA, and 3D rotational angiography before and after rupture to generate geometric models of the aneurysm and perianeurysmal vasculature. Intra-aneurysmal hemodynamics were simulated by using computational fluid dynamics. Two neuroradiologists qualitatively assessed flow complexity, flow stability, inflow concentration, and flow impingement in consensus, by using flow-velocity streamlines and wall shear stress distributions.ResultsHemodynamics changed in 6 of the 9 aneurysms. The median time between imaging before and after rupture was 678 days (range, 14-1461 days) in these 6 cases, compared with 151 days (range, 34-183 days) in the 3 cases with unaltered hemodynamics. Changes were observed for flow complexity (n = 3), flow stability (n = 3), inflow concentration (n = 2), and region of flow impingement (n = 3). These changes were in all instances associated with aneurysm displacement due to rupture-related hematomas, growth, or newly formed lobulations.ConclusionsHemodynamic characteristics of intracranial aneurysms can be altered by geometric changes before, during, or just after rupture. Associations of hemodynamic characteristics with aneurysm rupture obtained from case-control studies comparing ruptured with unruptured aneurysms should therefore be interpreted with caution.
| S-EPMC7965049 | biostudies-literature
Project description:Background Both meteorological factors and morphological factors are important factors to predict intracranial aneurysm rupture. This study investigated the relationship between meteorological factors and aneurysmal subarachnoid hemorrhage (aSAH). Additionally, the morphological differences between ruptured and unruptured aneurysms under these high-risk meteorological conditions were assessed. Methods and Results The records of 1751 patients with aSAH with 2124 intracranial aneurysms were retrospectively analyzed. Spearman rank correlation analysis was used to assess the risks of incident aSAH on the basis of daily meteorological data. Morphological parameters were analyzed using 1-way ANOVA tests, and significant parameters (P<0.05) were further examined using a multivariable logistic regression analysis. Daily aSAH incidence had significant negative correlations with daily mean, maximum, and minimum temperature (P<0.001) and a significant positive correlation with daily mean atmospheric pressure (P<0.001). Additionally, 58 patients with multiple aneurysms were assessed to determine morphological differences. There were significant differences in the mean values for aneurysm size, neck width, length, height, width, parent artery diameter, shape of the aneurysm, aspect ratio, size ratio, and bottleneck factor (P<0.05). The multivariable logistic regression analysis showed that aspect ratio (β=1.277, odds ratio=3.585, 95% CI, 1.588-8.090; P=0.002) was an independent risk factor for aneurysm rupture. Receiver operating characteristic curve analysis indicated that the ruptured aneurysm threshold of size was 3.45 mm and aspect ratio was 1.05. Conclusions Lower daily mean, maximum, and minimum temperatures and a higher daily mean atmospheric pressure were associated with an increased rate of aSAH. Additionally, under these meteorological conditions, the aneurysm size and aspect ratio thresholds for predicting rupture of an aneurysm may be lower.
| S-EPMC6755857 | biostudies-other
Project description:BACKGROUND AND PURPOSE:Many ruptured intracranial aneurysms (IAs) are small. Clinical presentations suggest that small and large IAs could have different phenotypes. It is unknown if small and large IAs have different characteristics that discriminate rupture. METHODS:We analyzed morphological, hemodynamic, and clinical parameters of 413 retrospectively collected IAs (training cohort; 102 ruptured IAs). Hierarchal cluster analysis was performed to determine a size cutoff to dichotomize the IA population into small and large IAs. We applied multivariate logistic regression to build rupture discrimination models for small IAs, large IAs, and an aggregation of all IAs. We validated the ability of these 3 models to predict rupture status in a second, independently collected cohort of 129 IAs (testing cohort; 14 ruptured IAs). RESULTS:Hierarchal cluster analysis in the training cohort confirmed that small and large IAs are best separated at 5 mm based on morphological and hemodynamic features (area under the curve=0.81). For small IAs (<5 mm), the resulting rupture discrimination model included undulation index, oscillatory shear index, previous subarachnoid hemorrhage, and absence of multiple IAs (area under the curve=0.84; 95% confidence interval, 0.78-0.88), whereas for large IAs (?5 mm), the model included undulation index, low wall shear stress, previous subarachnoid hemorrhage, and IA location (area under the curve=0.87; 95% confidence interval, 0.82-0.93). The model for the aggregated training cohort retained all the parameters in the size-dichotomized models. Results in the testing cohort showed that the size-dichotomized rupture discrimination model had higher sensitivity (64% versus 29%) and accuracy (77% versus 74%), marginally higher area under the curve (0.75; 95% confidence interval, 0.61-0.88 versus 0.67; 95% confidence interval, 0.52-0.82), and similar specificity (78% versus 80%) compared with the aggregate-based model. CONCLUSIONS:Small (<5 mm) and large (?5 mm) IAs have different hemodynamic and clinical, but not morphological, rupture discriminants. Size-dichotomized rupture discrimination models performed better than the aggregate model.
| S-EPMC5871584 | biostudies-literature
Project description:BACKGROUND AND PURPOSE:Both low serum calcium and magnesium levels have been associated with the extent of bleeding in patients with intracerebral hemorrhage, suggesting hypocalcemia- and hypomagnesemia-induced coagulopathy as a possible underlying mechanism. We hypothesized that serum albumin-corrected total calcium and magnesium levels are associated with ruptured intracranial aneurysms. METHODS:The medical records of 4701 patients, including 1201 prospective patients, diagnosed at the Brigham and Women's Hospital and Massachusetts General Hospital between 1990 and 2016 were reviewed and analyzed. One thousand two hundred seventy-five patients had available serum calcium, magnesium, and albumin values within 1 day of diagnosis. Individuals were divided into cases with ruptured aneurysms and controls with unruptured aneurysms. Univariable and multivariable logistic regression analyses were performed to determine the association between serum albumin-corrected total calcium and magnesium levels and ruptured aneurysms. RESULTS:In multivariable analysis, both albumin-corrected calcium (odds ratio, 0.33; 95% confidence interval, 0.27-0.40) and magnesium (odds ratio, 0.40; 95% confidence interval, 0.28-0.55) were significantly and inversely associated with ruptured intracranial aneurysms. CONCLUSIONS:In this large case-control study, hypocalcemia and hypomagnesemia at diagnosis were significantly associated with ruptured aneurysms. Impaired hemostasis caused by hypocalcemia and hypomagnesemia may explain this association.
| S-EPMC6019530 | biostudies-literature
Project description:Background and purposeRupture risk assessment for intracranial aneurysms remains challenging, and risk factors, including wall shear stress, are discussed controversially. The primary purpose of the presented challenge was to determine how consistently aneurysm rupture status and rupture site could be identified on the basis of computational fluid dynamics.Materials and methodsTwo geometrically similar MCA aneurysms were selected, 1 ruptured, 1 unruptured. Participating computational fluid dynamics groups were blinded as to which case was ruptured. Participants were provided with digitally segmented lumen geometries and, for this phase of the challenge, were free to choose their own flow rates, blood rheologies, and so forth. Participants were asked to report which case had ruptured and the likely site of rupture. In parallel, lumen geometries were provided to a group of neurosurgeons for their predictions of rupture status and site.ResultsOf 26 participating computational fluid dynamics groups, 21 (81%) correctly identified the ruptured case. Although the known rupture site was associated with low and oscillatory wall shear stress, most groups identified other sites, some of which also experienced low and oscillatory shear. Of the 43 participating neurosurgeons, 39 (91%) identified the ruptured case. None correctly identified the rupture site.ConclusionsGeometric or hemodynamic considerations favor identification of rupture status; however, retrospective identification of the rupture site remains a challenge for both engineers and clinicians. A more precise understanding of the hemodynamic factors involved in aneurysm wall pathology is likely required for computational fluid dynamics to add value to current clinical decision-making regarding rupture risk.
| S-EPMC8013045 | biostudies-literature
Project description:BackgroundA simple dimensionless aneurysm number ($An$), which depends on geometry and flow pulsatility, was previously shown to distinguish the flow mode in intracranial aneurysms (IA): vortex mode with a dynamic vortex formation/evolution if $An > 1$, and cavity mode with a steady shear layer if $An < 1$.ObjectiveTo hypothesize that $An\ > \ 1$ can distinguish rupture status because vortex mode is associated with high oscillatory shear index, which, in turn, is statistically associated with rupture.MethodsThe above hypothesis is tested on a retrospective, consecutively collected database of 204 patient-specific IAs. The first 119 cases are assigned to training and the remainder to testing dataset. $An$ is calculated based on the pulsatility index (PI) approximated either from the literature or solving an optimization problem (denoted as$\ \widehat {PI}$). Student's t-test and logistic regression (LR) are used for hypothesis testing and data fitting, respectively.Results$An$ can significantly discriminate ruptured and unruptured status with 95% confidence level (P < .0001). $An$ (using PI) and $\widehat {An}$ (using $\widehat {PI}$) significantly predict the ruptured IAs (for training dataset $An\!:\ $AUC = 0.85, $\widehat {An}\!:\ $AUC = 0.90, and for testing dataset $An\!:\ $sensitivity = 94%, specificity = 33%, $\widehat {An}\!:\ $sensitivity = 93.1%, specificity = 52.85%).Conclusion$An > 1$ predicts ruptured status. Unlike traditional hemodynamic parameters such as wall shear stress and oscillatory shear index, $An$ has a physical threshold of one (does not depend on statistical analysis) and does not require time-consuming flow simulations. Therefore, $An$ is a simple, practical discriminator of IA rupture status.
| S-EPMC7566542 | biostudies-literature
Project description:Angiotensin II (Ang II) stimulates vascular inflammation, oxidative stress, and formation and rupture of intracranial aneurysms in mice. Because Ang 1-7 acts on Mas receptors and generally counteracts deleterious effects of Ang II, we tested the hypothesis that Ang 1-7 attenuates formation and rupture of intracranial aneurysms. Intracranial aneurysms were induced in wild-type and Mas receptor-deficient mice using a combination of Ang II-induced hypertension and intracranial injection of elastase in the basal cistern. Mice received elastase+Ang II alone or a combination of elastase+Ang II+Ang 1-7. Aneurysm formation, prevalence of subarachnoid hemorrhage, mortality, and expression of molecules involved in vascular injury were assessed. Systolic blood pressure was similar in mice receiving elastase+Ang II (mean±SE, 148±5 mm Hg) or elastase+Ang II+Ang 1-7 (144±5 mm Hg). Aneurysm formation was also similar in mice receiving elastase+Ang II (89%) or elastase+Ang II+Ang 1-7 (84%). However, mice that received elastase+Ang II+Ang 1-7 had reduced mortality (from 64% to 36%; P<0.05) and prevalence of subarachnoid hemorrhage (from 75% to 48%; P<0.05). In cerebral arteries, expression of the inflammatory markers, Nox2 and catalase increased similarly in elastase+Ang II or elastase+Ang II+Ang 1-7 groups. Ang 1-7 increased the expression of cyclooxygenase-2 and decreased the expression of matrix metalloproteinase-9 induced by elastase+Ang II (P<0.05). In Mas receptor-deficient mice, systolic blood pressure, mortality, and prevalence of subarachnoid hemorrhage were similar (P>0.05) in groups treated with elastase+Ang II or elastase+Ang II+Ang 1-7. The expression of Mas receptor was detected by immunohistochemistry in samples of human intracranial arteries and aneurysms. In conclusion, without attenuating Ang II-induced hypertension, Ang 1-7 decreased mortality and rupture of intracranial aneurysms in mice through a Mas receptor-dependent pathway.
| S-EPMC4096422 | biostudies-literature
Project description:Background and purposePhenotypic modulation of vascular smooth muscle cells (VSMCs) plays an important role in the development of intracranial aneurysms (IAs). Growing evidence has demonstrated that circular RNAs (circRNAs) may serve as a potential modulator of VSMC phenotype in various vascular diseases. This study aimed to assess the potential function of circRNAs in the rupture of IAs and VSMC phenotypic modulation.MethodsUsing surgically dissected human ruptured (n = 8) and unruptured (n = 8) IA lesions, differentially expressed circRNAs were screened by transcriptomic sequencing and verified using qRT-PCR. Based on the screened circRNA, we predicted and screened the combined miRNA and downstream mRNAs to construct circRNA-miRNA-mRNA networks. Further in vitro experiments were performed to investigate the relationship between the validated circRNA and the phenotypic switching of VSMCs.ResultsWe found 1,373 differentially expressed genes in ruptured versus unruptured aneurysms. The top five dysregulated circRNAs were selected for qRT-PCR validation. We found hsa_circ_0031608 was both highly expressed in ruptured IAs and pro-inflammatory transformation of VSMCs. Then, a regulatory circRNA-miRNA-mRNA with one circRNA node, six miRNA nodes, and 84 mRNA nodes was constructed. GO analysis and KEGG pathway enrichment analysis were performed on mRNAs in the network. Then, a PPI network was built based on these mRNAs and five hub genes were identified (FOXO3, DICER1, CCND2, IGF1R, and TNRC6B) by the cytoHubba plugin in Cytoscape software. In vitro, overexpression of hsa_circ_0031608 influenced the expression of VSMC phenotypic markers validated by qPCR and Western blotting. Furthermore, hsa_circ_0031608 promoted the migration and proliferation capacity of VSMCs.Conclusionhsa_circ_0031608 regulated the phenotypic modulation of VSMCs and played an important role in the rupture of IAs. The specific mechanism should be further studied and confirmed.
| S-EPMC8963354 | biostudies-literature
Project description:We aimed to develop and validate a morphology-based radiomics signature nomogram for assessing the risk of intracranial aneurysm (IA) rupture. A total of 254 aneurysms in 105 patients with subarachnoid hemorrhage and multiple intracranial aneurysms from three centers were retrospectively reviewed and randomly divided into the derivation and validation cohorts. Radiomics morphological features were automatically extracted from digital subtraction angiography and selected by the least absolute shrinkage and selection operator algorithm to develop a radiomics signature. A radiomics signature-based nomogram was developed by incorporating the signature and traditional morphological features. The performance of calibration, discrimination, and clinical usefulness of the nomogram was assessed. Ten radiomics morphological features were selected to build the radiomics signature model, which showed better discrimination with an area under the curve (AUC) equal to 0.814 and 0.835 in the derivation and validation cohorts compared with 0.747 and 0.666 in the traditional model, which only include traditional morphological features. When radiomics signature and traditional morphological features were combined, the AUC increased to 0.842 and 0.849 in the derivation and validation cohorts, thus showing better performance in assessing aneurysm rupture risk. This novel model could be useful for decision-making and risk stratification for patients with IAs.
| S-EPMC8148474 | biostudies-literature