Aneurysm Formation In Patients Research Articles

Association of monocyte to HDL cholesterol ratio and a composite risk score with left ventricular aneurysm formation in patients with acute ST-segment elevation myocardial infarction.

Left ventricular aneurysm (LVA) is an important complication of acute myocardial infarction. This study aimed to investigate the potential predictive value of the monocyte count to high-density lipoprotein cholesterol ratio (MHR) and a composite risk score in determining the formation of LVA in patients with acute ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention. We recruited 1005 consecutive patients with STEMI. Multivariable logistic regression analysis was conducted identify the independent risk factors for LVA formation. Predictive power of MHR and composite risk score for LVA formation were assessed using receiver operating characteristic curve analysis. The MHR was significantly higher among patients with LVA compared to those without LVA [6.6 (3.8-10.8) vs. 4.6 (3.3-6.3), P < 0.001]. Univariable logistic regression analysis revealed that MHR (OR = 3.866, 95% CI = 2.677-5.582, P < 0.001) was associated with the risk of LVA formation. The predictive value of MHR remained significant even after multivariate logistic regression analysis [odds ratio (OR) = 4.801, 95% confidence interval (CI) = 2.672-8.629, P < 0.001]. The discriminant power of MHR for LVA is 0.712, which is superior to both monocyte (C statistic = 0.553) and high-density lipoprotein cholesterol (C statistic = 0.654). The composite risk score including MHR, gender, LVEF, hemoglobin, lymphocyte and left anterior descending artery as the culprit vessel could significantly increase the predictive ability (C statistic = 0.920). A higher MHR could effectively identify individuals at high risk of LVA formation, especially when combined with gender, LVEF, hemoglobin, lymphocyte and left anterior descending artery as the culprit vessel.

Left ventricular aneurysm formation in patients with takotsubo syndrome: A peculiar phenomenon with subtle implications.

Left ventricular aneurysm formation in patients with takotsubo syndrome: A peculiar phenomenon with subtle implications.

Risk of de novo aneurysm formation in patients previously diagnosed with a ruptured or unruptured aneurysm: 18-year follow-up

BackgroundData on de novo aneurysm formation after treatment for intracranial aneurysms remains scarce. We studied the incidence of de novo aneurysm formation in patients who had undergone aneurysm treatment more than 18 years prior to follow-up. As it is a disease affecting a younger patient population more specific guidelines are needed when planning a follow-up regime. MethodsThe rate of de novo aneurysm formation was assessed with Magnetic Resonance Angiography (MRA) follow-up >18 years after endovascular or microsurgical treatment for an intracranial aneurysm. Variables associated with de novo aneurysm formation were studied using logistic regression. Missing data were imputed using chained random forests. A data-driven model for the prediction of de novo aneurysm was created to calculate the relative variable importance of ten clinical features. ResultsDe novo aneurysms were identified in 11/81 (13.6 %) patients, of whom 1 was male, over a median follow-up of 20 years. Sex was the most important variable associated with de novo aneurysm formation. Regarding the development of de novo aneurysm, men displayed an odds ratio (OR) of 0.16 (0.01–0.97), compared with women. OR for mRS score 2 or more was 0.20 (95 % CI 0.01–1.34), and OR for smokers was 3.70 (0.54–31.18). Six out of 11 patients (54.5 %) needed treatment; 1 underwent endovascular treatment (EVT) and 5 underwent microsurgical treatment (MST). The overall annual de novo aneurysm formation rate was 0.92 %. ConclusionsThis study highlights the need for a longer follow-up imaging monitoring of patients that have previously undergone treatment for an intracranial aneurysm. These data are useful to take into consideration when planning a follow-up strategy.

Left ventricular aneurysm formation in patients with Takotsubo syndrome: A peculiar phenomenon with subtle implications. Author's reply.

Left ventricular aneurysm formation in patients with Takotsubo syndrome: A peculiar phenomenon with subtle implications. Author's reply.

Reduced Levels of Selenium and Thioredoxin Reductase in the Thoracic Aorta Could Contribute to Aneurysm Formation in Patients with Marfan Syndrome

Marfan syndrome (MFS) is an autosomal dominant disorder caused by a heterozygous mutation of the FBN1 gene. MFS patients present oxidative stress that disturbs redox homeostasis. Redox homeostasis depends in part on the enzymatic antioxidant system, which includes thioredoxin reductase (TrxR) and glutathione peroxidases (GPx), both of which require an adequate concentration of selenium (Se). Therefore, the aim of this study was to determine if Se levels are decreased in the TAA of patients with MFS since this could contribute to the formation of an aneurysm in these patients. The results show that interleukins IL-1β, IL-6 TGF-β1, and TNF-α (p ≤ 0.03), and carbonylation (p ≤ 0.03) were increased in the TAA of patients with MFS in comparison with control subjects, while Se, thiols (p = 0.02), TrxR, and GPx (p ≤ 0.001) were decreased. TLR4 and NOX1 (p ≤ 0.03), MMP9 and MMP2 (p = 0.04) and NOS2 (p &lt; 0.001) were also increased. Therefore, Se concentrations are decreased in the TAA of MFS, which can contribute to a decrease in the activities of TrxR and GPx, and thiol groups. A decrease in the activities of these enzymes can lead to the loss of redox homeostasis, which can, in turn, lead to an increase in the pro-inflammatory interleukins associated with the overexpression of MMP9 and MMP2.

Histopathological Characterization of Abdominal Aortic Aneurysms from Patients with Multiple Aneurysms Compared to Patients with a Single Abdominal Aortic Aneurysm.

The aim of this study was to investigate histopathological differences in abdominal aortic aneurysms (AAAs) between patients with multiple and single arterial aneurysms, as we suspect that there are different underlying mechanisms in aneurysm formation. Analysis was based on a previous retrospective study on patients with multiple arterial aneurysms (mult-AA; defined as at least four, n = 143) and a single AAA (sing-AAA, n = 972) who were admitted to our hospital for treatment between 2006 and 2016. Available paraffin-embedded AAA wall specimens were derived from the Vascular Biomaterial Bank Heidelberg (mult-AA, n = 12 vs. sing-AAA, n = 19). Sections were analyzed regarding structural damage of the fibrous connective tissue and inflammatory cell infiltration. Alterations to the collagen and elastin constitution were assessed by Masson-Goldner trichrome and Elastica van Gieson staining. Inflammatory cell infiltration, response and transformation were assessed by CD45 and IL-1β immunohistochemistry and von Kossa staining. The extent of aneurysmal wall alterations was assessed by semiquantitative gradings and was compared between the groups using Fisher's exact test. IL-1β was significantly more present in the tunica media in mult-AA compared to sing-AAA (p = 0.022). The increased expression of IL-1β in mult-AA compared to sing-AAA indicates inflammatory processes play a role in aneurysm formation in patients with multiple arterial aneurysms.

The prognosis and treatment effectiveness of de novo aneurysm formation after radiation therapy for brain tumor.

Radiation therapy is a well-established, minimally invasive method of treating brain tumors. In recent years, the number of post-radiotherapy patients has increased, and delayed side effects are evident. De novo aneurysm formation after radiation often manifests as fatal subarachnoid hemorrhage (SAH), resulting in severe clinical outcomes. Nevertheless, the prognosis and therapeutic efficacy of radiation-induced aneurysms (RIAs) remain unclear. Using the PubMed database from 1980 to 2021, we screened 45 articles (53 individual cases) on RIAs; approximately 70% of RIAs were diagnosed after rupture. Of 38 ruptured RIAs, 12 (31.6%) had modified Rankin scale (mRS) 5-6. On the other hand, all unruptured RIAs (15 cases) recovered without neurological deficits (p = 0.012). Ten of the 39 ruptured RIAs were treated surgically, and 22 were treated endovascularly. There was no significant difference in mRS between treatment modalities (p = 0.393), but conservative therapy was significantly related to unfavorable outcomes (p = 0.025). To improve clinical outcomes, RIAs need to be diagnosed before rupture. Surgeons should be aware of de novo aneurysm formation in patients long after radiation therapy.

Oxidative Stress-Related Susceptibility to Aneurysm in Marfan’s Syndrome

The involvement of highly reactive oxygen-derived free radicals (ROS) in the genesis and progression of various cardiovascular diseases, including arrhythmias, aortic dilatation, aortic dissection, left ventricular hypertrophy, coronary arterial disease and congestive heart failure, is well-established. It has also been suggested that ROS may play a role in aortic aneurysm formation in patients with Marfan’s syndrome (MFS). This syndrome is a multisystem disorder with manifestations including cardiovascular, skeletal, pulmonary and ocular systems, however, aortic aneurysm and dissection are still the most life-threatening manifestations of MFS. In this review, we will concentrate on the impact of oxidative stress on aneurysm formation in patients with MFS as well as on possible beneficial effects of some agents with antioxidant properties. Mechanisms responsible for oxidative stress in the MFS model involve a decreased expression of superoxide dismutase (SOD) as well as enhanced expression of NAD(P)H oxidase, inducible nitric oxide synthase (iNOS) and xanthine oxidase. The results of studies have indicated that reactive oxygen species may be involved in smooth muscle cell phenotype switching and apoptosis as well as matrix metalloproteinase activation, resulting in extracellular matrix (ECM) remodeling. The progression of the thoracic aortic aneurysm was suggested to be associated with markedly impaired aortic contractile function and decreased nitric oxide-mediated endothelial-dependent relaxation.

Abstract MP24: Disruption Of Actin Remodeling Intensifies Aneurysm-promoting Signals In Smooth Muscle Cells

Mutations within proteins coding for extracellular matrix assembly or those in the transforming growth factor beta (TGFβ) signaling pathway lead to aneurysm formation in patients and mice. As the SMC cytoskeletal network is intricately linked to TGFβ and ECM signaling, we sought to determine if disruption of the cytoskeletal filaments would alter how SMCs respond to angiotensin II, an important mediator of aneurysm formation. C57BL/6 mice lacking Tgbfr1 in SMCs (SMC- Tgbr1 iko ) generated by Jiang et al. have been shown to develop rapid and severe aortic aneurysm degeneration with 100% penetrance. Analysis was conducted on aneurysm and control mouse and human aortic tissue sections. We observed that SMC- Tgbr1 iko mice had reduced expression of filamentous (f-) and α-actin protein in the aortic media than control mice. Primary Tgbr1 iko SMCs also had higher levels of pRelA expression, less α-actin mRNA, and less f-actin than control SMCs. Tissue sections from aneurysm patients had reduced f-actin staining relative to controls. Disruption of f-actin with the destabilizer latrunculin A in vitro led to increased RelA and ERK activation in the presence of AngII, which was further augmented in the presence of a neutralizing antibody for TGFβ. In contrast, jasplakinolide—an f-actin stabilizer—prevented TGFβ blockade induced pRelA expression, suggesting that altered/inhibited TGFβ signaling modulates NFkB through actin depolymerization. While stabilization and disruption of microtubules led to RelA activation, no effect was observed on TGFβ blockade-induced pRelA expression. The phosphoantibody array revealed that f-actin disruption in the presence of AngII activated the CREB, AKT1/2/3, ERK1/2, and STAT3 pathways in mouse aortic SMCs. SMC- Tgbr1 iko mice treated with cytochalasin B suffered significantly greater mortality and had increased aortic growth over a 30-day follow-up period. Aortic aneurysms are coincident with reduced f-actin expression in murine and human aortic SMCs. Chemical deconstruction of actin filaments promotes an inflammatory phenotype in mouse SMCs in vitro , and aggravates aneurysm formation in vivo . Aberrant or inhibited TGFβ signaling potentiates NFkB activation in SMCs, which may be dependent on f-actin disassembly.

Intraindividual comparison of 1.5 T and 3 T non-contrast MR angiography for monitoring of aortic root diameters in Marfan patients

BackgroundReproducible aortic diameter measurements are crucial for assessment of aortic growth and aneurysm formation in patients with Marfan syndrome. The objective of this study was to perform an intraindividual comparison of aortic measurements at 1.5 T and 3 T using non-contrast magnetic resonance angiography (MRA) in pre-surgical and post-surgical Marfan patients. MethodsForty consecutive Marfan patients were retrospectively evaluated by ECG-gated 2D balanced steady-state free precession (bSSFP) MRA at 1.5 T and 3 T after 363 ± 58 days. 24 patients were before and 16 patients after aortic root surgery. Two readers independently measured aortic diameters at seven aortic levels and rated the image quality/image artifacts (1 = poor/severe, 4 = excellent/none). Contrast-to-noise ratio (CNR) and signal intensity slopes between aortic lumen and vessel walls were semiautomatically determined. ResultsIn pre-surgical Marfan patients, interobserver agreement of aortic root diameter measurements was significantly higher at 3 T compared to 1.5 T (p < 0.05). In post-surgical Marfan patients, image quality and artifacts were significantly worse at 3 T compared to 1.5 T (p < 0.05). CNR was higher at 3 T compared to 1.5 T at all aortic levels. Significantly steeper slopes of signal intensity curves were observed at 3 T at all aortic levels (p < 0.001). ConclusionsIn pre-surgical Marfan patients, non-contrast MRA provides higher reproducibility of aortic diameter measurements at 3 T compared to 1.5 T. In post-surgical Marfan patients, metallic implants result in significantly worse imaging artifacts and reduced image quality at 3 T compared to 1.5 T. Therefore, we propose to monitor the thoracic aorta with non-contrast MRA at 3 T in pre-surgical Marfan patients and at 1.5 T in post-surgical Marfan patients.

Aspirin treatment prevents inflammation in experimental bifurcation aneurysms in New Zealand White rabbits

BackgroundAneurysm wall degeneration is linked to growth and rupture. To address the effect of aspirin (ASA) on aneurysm formation under various wall conditions, this issue was analyzed in a novel...

Dysregulation of Endothelial Nitric Oxide Synthase Does Not Depend on Hemodynamic Alterations in Bicuspid Aortic Valve Aortopathy.

BackgroundBicuspid aortic valves (BAVs) predispose to ascending aortic aneurysm. Turbulent blood flow and genetic factors have been proposed as underlying mechanisms. Endothelial nitric oxide synthase (eNOS) has been implicated in BAV aortopathy, and its expression is regulated by wall shear stress. We hypothesized that if turbulent flow induces aneurysm formation in patients with a BAV, regional differences in eNOS expression would be observed in BAVs.Methods and ResultsAscending aortic specimens were harvested intraoperatively from 48 patients with tricuspid aortic valve (19 dilated, 29 nondilated) and 38 with BAV (28 dilated, 10 nondilated) undergoing cardiac surgery. eNOS mRNA and protein concentration were analyzed at the convex and concave aortic wall. In nondilated aortas, eNOS mRNA and protein concentration were decreased in BAV compared with tricuspid aortic valve (all P<0.05). eNOS expression was increased in association with dilation in BAV aortas (P=0.03), but not in tricuspid aortic valve aortas (P=0.63). There were no regional differences in eNOS mRNA or protein concentration in BAV aortas (all P>0.05). However, eNOS expression was increased at the concave wall (versus convexity) in tricuspid aortic valve dilated aortas (all P<0.05).ConclusionsDysregulated eNOS occurs independent of dilation in BAV aortas, suggesting a potential role for aberrantly regulated eNOS expression in the development of BAV‐associated aneurysms. The absence of regional variations of eNOS expression suggests that eNOS dysregulation in BAV aortas is the result of underlying genetic factors associated with BAV disease, rather than changes stimulated by hemodynamic alterations. These findings provide insight into the underlying mechanisms of aortic dilation in patients with a BAV.

Predictive risk factors of early onset left ventricular aneurysm formation in patients with acute ST-elevation myocardial infarction

BackgroundLeft ventricular aneurysm (LVA) is a severe complication of ST-elevation myocardial infarction (STEMI) and is associated with poor prognosis due to high mortality. However, predictors of LVA formation in early period are inadequately defined. ObjectivesThe purpose of this study is to determine potential predictors of LVA formation in early period (<15 days after admission) after acute STEMI. MethodsThe present study was retrospectively conducted involving 1823 STEMI patients based on the AMI database of our clinic between January 2013 and April 2019. Among STEMI patients with regional wall motion abnormality (RWMA), the baseline, angiographic, procedural characteristics of patients with early-onset LVA and controls without LVA were compared. The controls were matched 2:1 with LVA cases for the admission date. Patients with prior myocardial infarction, non-ischemic cardiomyopathy, severe heart valve disease, and patients without coronary angiography were excluded. The odds ratio (OR) and confidence interval (CI) were obtained by logistic regression analysis and all statistical analysis were performed by SPSS 25.0. ResultsAmong 1823 STEMI patients who underwent coronary angiography, 103 eligible patients (median age 67 years) had LVA and were compared to 206 patients without LVA (median age 60 years). In multivariate analysis, RWMA in the left ventricular anterior wall (OR 13.17, 95%CI 2.21–78.57, p=0.005) was found to be the most striking predictor of LVA, followed by RWMA in the apex (OR 7.93, 95%CI 2.22–28.30, p=0.001). Female sex (OR 3.91, 95%CI 1.54–9.93, p=0.004), peak N-terminal pro brain natriuretic peptide (NT-pro BNP,OR 1.08, 95%CI 1.01–1.16, p=0.031), time between onset of pain and balloon time (OR 1.01, 95%CI 1.00–1.01, P=0.016), and presence of QS-waves on initial electrocardiogram (OR 3.06, 95%CI 1.49–6.27, P=0.016) were independently associated with LVA formation. ConclusionThis study indicated that female sex, peak NT-pro BNP, the time between the onset of pain and balloon time, presence of QS-waves on initial electrocardiogram, RWMA of left ventricular anterior wall and apex were the independent predictors of early-onset LVA in patients with acute STEMI.

Risk of de novo aneurysm formation in patients with a prior diagnosis of ruptured or unruptured aneurysm: systematic review and meta-analysis.

De novo aneurysms are rare entities periodically discovered during follow-up imaging. Little is known regarding the frequency with which these lesions form or the time course. This systematic review and meta-analysis was undertaken to estimate the incidence of de novo aneurysms and to determine risk factors for aneurysm formation. The authors searched multiple databases for studies of patients with unruptured and ruptured aneurysms describing the rate of de novo aneurysm formation. The primary outcome was incidence of de novo aneurysm formation. A meta-analysis was performed using a random-effects model. The authors examined the associations of multiple aneurysms, prior subarachnoid hemorrhage, smoking, sex, age at presentation, and hypertension with de novo aneurysm formation. The meta-analysis included 14,968 aneurysm patients who received imaging follow-up from 35 studies. The overall incidence of de novo aneurysm formation was 2% (95% CI 2%-3%) over a mean follow-up time of 8.3 years. The estimated incidence density was 0.3%/patient-year. There was no statistically significant difference in rates of de novo aneurysm formation between patients who had ruptured aneurysms and those with unruptured aneurysms. In 8 studies, 11.2% of de novo aneurysms were found in patients with ≤ 5 years of follow-up and 88.8% were found at > 5 years. The mean time to rupture for de novo aneurysms was 10 years. This systematic review demonstrates that formation of de novo aneurysms is rare. Overall, routine screening for de novo aneurysms is likely to be of low yield and could be performed at time intervals of at least 5 to 10 years.

Hemodynamic characteristics associated with cerebral aneurysm formation in patients with carotid occlusion.

The pathogenesis of cerebral aneurysms in patients with internal carotid artery (ICA) occlusion is hypothesized to be hemodynamic. For the first time, the authors quantify the hemodynamic characteristics associated with aneurysm formation in patients with ICA occlusion. Records of patients with unilateral ICA stenosis or occlusion ≥ 90% who underwent hemodynamic assessment before treatment using quantitative MR angiography were retrospectively reviewed. The patients were classified into 2 groups based on the presence or absence of aneurysms. The hemodynamic parameters of flow volume rate, flow velocity, and wall shear stress (WSS) were measured in each vessel supplying collateral flow-bilateral A1 segments and bilateral posterior communicating arteries-and then compared between the groups. A total of 36 patients were included (8 with and 28 without aneurysms). The mean flow (72.3 vs 48.9 ml/min, p = 0.10), flow velocity (21.1 vs 12.7 cm/sec, p = 0.006), and WSS (22.0 vs 12.3 dynes/cm2, p = 0.003) were higher in the A1 segment contralateral to the side of the patent ICA in patients with versus without aneurysms. All de novo or growing aneurysms in our cohort were located on the anterior communicating artery (ACoA) or P1 segment. Flow velocity and WSS are significantly higher across the ACoA in patients who harbor an aneurysm, and de novo or growing aneurysms are often located on collateral vessels. Thus, robust primary collaterals after ICA occlusion may be a contributing factor in cerebral aneurysm formation.

Natural History of De Novo Aneurysm Formation in Patients with Treated Aneurysmatic Subarachnoid Hemorrhage: A Ten-Year Follow-Up

De novo aneurysm formation after completely occluded aneurysms via clipping or coiling has not been well studied. Although known to occur several years after initial aneurysm management, the natural history of de novo aneurysms is obscure. We investigated the formation of new aneurysms in patients who had previously undergone treatment of intracranial aneurysms. In a retrospective, single-institutional series, eligible patients who had undergone treatment of ruptured cerebral aneurysms from 2000 to 2011 were included. The primary outcome measure was the development of de novo aneurysms during long-term follow-up. Overall, 130 patients (63% women) who had undergone microsurgical clipping (n= 63; 48.5%) or endovascular coiling (n= 67%; 51.5%) for ruptured aneurysms were included. The average follow-up time for our cohort was 10 ± 2.7 years. De novo aneurysms occurred in 10 of 130 patients (7.7%), with a mean time of 7.9 years for aneurysm detection. No association between the formation of de novo aneurysms and the location of the treated aneurysms, smoking status, hypertension, age, or gender was found. Follow-up imaging studies were performed every 2 years. De novo aneurysms had formed in 2 patients within 2-5 years, 7 patients after 5-10 years, and 1 patient after 10 years of follow-up. In 2 of 10 patients, the de novo aneurysm had ruptured and led to subarachnoid haemorrhage. The rate of de novo aneurysm occurrence was 7.6%, with a mean time to development of 7.9 years. This underscores the significance of long-term monitoring of patients with intracranial aneurysms. In our series, most new aneurysms had occurred after 5 years of follow-up.

The mir-200 family regulates key pathogenic events in ascending aortas of individuals with bicuspid aortic valves.

BackgroundAn individual with a bicuspid aortic valve (BAV) runs a substantially higher risk of developing aneurysm in the ascending aorta compared to the normal population with tricuspid aortic valves (TAV). Aneurysm formation in patients with BAV and TAV is known to be distinct at the molecular level but the underlying mechanisms are undefined. Here, we investigated the still incompletely described role of microRNAs (miRNAs), important post‐transcriptional regulators of gene expression, in such aortic disease of patients with BAV as compared with TAV.Methods and ResultsUsing a system biology approach, based on data obtained from proteomic analysis of non‐dilated aortas from BAV and TAV patients, we constructed a gene‐interaction network of regulatory microRNAs associated with the observed differential protein signature. The miR‐200 family was the highest ranked miRNA, hence potentially having the strongest effect on the signalling network associated with BAV. Further, qRT‐PCR and ChIP analyses showed lower expression of miR‐200c, higher expression of miR‐200 target genes, ZEB1/ZEB2 transcription factors, and higher chromatin occupancy of the miR‐200c promoter by ZEB1/ZEB2 in BAV patients, indicating a miR‐200c/ZEBs negative feedback loop and induction of endothelial/epithelial mesenchymal transition (EndMT/EMT).ConclusionWe propose that a miR‐200‐dependent process of EndMT/EMT is a plausible biological mechanism rendering the BAV ascending aorta more prone to aneurysm development. Although initially supported by a miR‐200c/ZEB feedback loop, this process is most probably advanced by cooperation of other miRNAs.

Participation of Arachidonic Acid Metabolism in the Aortic Aneurysm Formation in Patients with Marfan Syndrome.

Marfan syndrome (MFS) is a pleiotropic genetic disease involving the cardiovascular system where a fibrillin-1 mutation is present. This mutation is associated with accelerated activation of transforming growth factor β (TGFβ1) which contributes to the formation of aneurysms in the root of the aorta. There is an imbalance in the synthesis of thromboxane A2 (TXA2) and prostacyclin, that is a consequence of a differential protein expression of the isoforms of cyclooxygenases (COXs), suggesting an alteration of arachidonic acid (AA) metabolism. The aim of this study was to analyze the participation of AA metabolism associated with inflammatory factors in the dilation and dissection of the aortic aneurysm in patients with MFS. A decrease in AA (p = 0.02), an increase in oleic acid (OA), TGFβ1, tumor necrosis factor alpha (TNFα), prostaglandin E2 (PGE2) (p < 0.05), and COXs activity (p = 0.002) was found. The expressions of phospholipase A2 (PLA2), cytochrome P450 (CYP450 4A), 5-lipoxygenase (5-LOX), COX2 and TXA2R (p < 0.05) showed a significant increase in the aortic aneurysm of patients with MFS compared to control subjects. COX1, 6-keto-prostaglandin 1 alpha (6-keto-PG1α) and 8-isoprostane did not show significant changes. Histological examination of the aortas showed an increase of cystic necrosis, elastic fibers and collagen in MFS. The results suggest that there are inflammatory factors coupled to genetic factors that predispose to aortic endothelial dysfunction in the aortic tissue of patients with MFS. There is a decrease in the percentage of AA, associated with an increase of PLA2, COX2/TXA2R, CYP450 4A, and 5-LOX which leads to a greater synthesis of PGE2 than of 6-keto-PGF1α, thus contributing to the formation of the aortic aneurysm. The evident loss of the homeostasis in these mechanisms confirms that there is a participation of the AA pathway in the aneurysm progression in MFS.

Risk of de novo aneurysm formation in patients with unruptured intracranial aneurysms.

The rate of de novo aneurysm formation in patients with unruptured aneurysm without history of subarachnoid hemorrhage is scarcely defined in literature. We report the incidence of de novo aneurysm formation in a large contemporary series of patients with unruptured intracranial aneurysm (UIA) undergoing serial neurovascular imaging. Neurovascular imaging studies of 321 consecutive UIA patients with no prior history of subarachnoid hemorrhage, with at least 3years of follow-up imaging, were reviewed by a neuroradiologist and a neurosurgeon. Rate of de novo aneurysm formation was reported on a per-patient and per-patient-year basis. Of the 321 included patients, three patients (0.9%) developed a de novo aneurysm over a mean follow-up period of 5.2years, for an incidence rate of 0.18% per patient-year. No de novo aneurysms ruptured and all three were 2mm in size. The rate of de novo aneurysm formation in patients with unruptured aneurysms and no history of subarachnoid hemorrhage is very low. These data are useful to advice patients with unruptured aneurysms from another aneurysm and to plan imaging follow-ups in these patients.

Circulating Interleukin-6 (IL-6) Associate with Aortic Dimensions in Genetic Aortic Conditions

Background: Biomarkers that reflect progression of dilatation of the aorta in patients with aortic conditions are needed as surrogate tools to assist in monitoring the condition in a non-invasive manner in combination with imaging procedures but are yet to be established. This study aimed to establish clinically useful biomarkers for aortic conditions in patients enrolled in the Genetically-Triggered Thoracic Aortic Conditions (GenTAC) registry. Methods: Plasma samples of 159 patients enrolled in the GenTAC registry were assessed for circulating biomarkers (interleukin-6 (IL-6), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP1), tissue inhibitor of metalloproteinase-2 (TIMP-2) and transforming growth factor-β1 (TGF β1)] by enzyme-linked immunosorbent assay. Primary diagnosis and aortic image data were compared with the measured values. Results: IL-6 showed significant positive correlations with aortic dimensions at each segment of the aorta, the correlation becoming stronger as it shifts to distal (ascending aorta R=0.26 p=0.004, proximal arch R=0.35 p<0.0001, transverse arch R=0.30 p=0.0005, mid-descending thoracic aorta R=0.40 p<0.0001, thoracoabdominal aorta R=0.38 p<0.0001, suprarenal abdominal aorta R=0.42 p<0.0001, and infrarenal aorta R=0.43 p<0.0001). TIMP-1 also showed a significant correlation albeit weaker, also exhibiting stronger correlation towards the distal end. Conclusion: Circulating IL-6 and TIMP-1 were associated with aortic dimensions in the aortopathies as registered in the GenTAC cohort. Our results provide support that IL-6 and TIMP-1 are associated with aortic aneurysm formation in patients with genetically-triggered thoracic aortic conditions.