RGS1 regulates myeloid cell accumulation in atherosclerosis and aortic aneurysm rupture through altered chemokine signalling.
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ABSTRACT:
SUBMITTER: Patel J
PROVIDER: S-EPMC4374153 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Abdominal aortic aneurysms (AAAs) are prevalent with aging, and AAA rupture is associated with increased mortality. There is currently no effective medical therapy to prevent AAA rupture. The monocyte chemoattractant protein (MCP-1)/C-C chemokine receptor type 2 (CCR2) axis critically regulates AAA inflammation, matrix-metalloproteinase (MMP) production, and extracellular matrix (ECM) stability. We therefore hypothesized that a diet intervention that can modulate CCR2 axis may therapeutically impact AAA risk of rupture. Since ketone bodies (KBs) can trigger repair mechanisms in response to inflammation, we evaluated whether systemic ketosis in vivo could reduce CCR2 and AAA progression. Male Sprague-Dawley rats underwent surgical AAA formation using porcine pancreatic elastase and received daily β-aminopropionitrile to promote AAA rupture. Rats with AAAs received either a standard diet, ketogenic diet (KD), or exogenous KBs (EKB). Rats receiving KD and EKB reached a state of ketosis and had significant reduction in AAA expansion and incidence of rupture. Ketosis also led to significantly reduced aortic CCR2 content, improved MMP balance, and reduced ECM degradation. Consistent with these findings, we also observed that Ccr2-/- mice have significantly reduced AAA expansion and rupture. In summary, this study demonstrates that CCR2 is essential for AAA expansion, and that its modulation with ketosis can reduce AAA pathology. This provides an impetus for future clinical studies that will evaluate the impact of ketosis on human AAA disease.
| S-EPMC10791699 | biostudies-literature
Project description:Both asthma and abdominal aortic aneurysms (AAA) involve inflammation. It remains unknown whether these diseases interact.Databases analyzed included Danish National Registry of Patients, a population-based nationwide case-control study included all patients with ruptured AAA and age- and sex-matched AAA controls without rupture in Denmark from 1996 to 2012; Viborg vascular trial, subgroup study of participants from the population-based randomized Viborg vascular screening trial. Patients with asthma were categorized by hospital diagnosis, bronchodilator use, and the recorded use of other anti-asthma prescription medications. Logistic regression models were fitted to determine whether asthma associated with the risk of ruptured AAA in Danish National Registry of Patients and an independent risk of having an AAA at screening in the Viborg vascular trial. From the Danish National Registry of Patients study, asthma diagnosed <1 year or 6 months before the index date increased the risk of AAA rupture before (odds ratio [OR]=1.60-2.12) and after (OR=1.51-2.06) adjusting for AAA comorbidities. Use of bronchodilators elevated the risk of AAA rupture from ever use to within 90 days from the index date, before (OR=1.10-1.37) and after (OR=1.10-1.31) adjustment. Patients prescribed anti-asthma drugs also showed an increased risk of rupture before (OR=1.12-1.79) and after (OR=1.09-1.48) the same adjustment. In Viborg vascular trial, anti-asthmatic medication use associated with increased risk of AAA before (OR=1.45) or after adjustment for smoking (OR=1.45) or other risk factors (OR=1.46).Recent active asthma increased risk of AAA and ruptured AAA. These findings document and furnish novel links between airway disease and AAA, 2 common diseases that share inflammatory aspects.
| S-EPMC4767565 | biostudies-literature
Project description:Aortic aneurysm is a leading cause of death in adults, often taking lives without any premonitory signs or symptoms. Adverse clinical outcomes of aortic aneurysm are preventable by elective surgical repair; however, identifying at-risk individuals is difficult. The objective of this study was to perform a predictive biomechanical analysis of ascending aortic aneurysm (AsAA) tissue to assess rupture risk on a patient-specific level. AsAA tissues, obtained intra-operatively from 50 patients, were subjected to biaxial mechanical and uniaxial failure tests to obtain their passive elastic mechanical properties. A novel analytical method was developed to predict the AsAA pressure-diameter response as well as the aortic wall yield and failure responses. Our results indicated that the mean predicted AsAA diameter at rupture was 5.6 ± 0.7 cm, and the associated blood pressure to induce rupture was 579.4 ± 214.8 mmHg. Statistical analysis showed significant positive correlation between aneurysm tissue compliance and predicted risk of rupture, where patients with a pressure-strain modulus ?100 kPa may be nearly twice as likely to experience rupture than patients with more compliant aortic tissue. The mechanical analysis of pre-dissection patient tissue properties established in this study could predict the "future" onset of yielding and rupture in AsAA patients. The analysis results implicate decreased tissue compliance as a risk factor for AsAA rupture. The presented methods may serve as a basis for the development of a pre-operative planning tool for AsAA evaluation, a tool currently unavailable.
| S-EPMC3872822 | biostudies-literature
Project description:BackgroundClinical and imaging surveillance practices following endovascular aneurysm repair (EVAR) for intact abdominal aortic aneurysm (AAA) vary considerably and compliance with recommended lifelong surveillance is poor. The aim of this study was to develop a dynamic prognostic model to enable stratification of patients at risk of future secondary aortic rupture or the need for intervention to prevent rupture (rupture-preventing reintervention) to enable the development of personalized surveillance intervals.MethodsBaseline data and repeat measurements of postoperative aneurysm sac diameter from the EVAR-1 and EVAR-2 trials were used to develop the model, with external validation in a cohort from a single-centre vascular database. Longitudinal mixed-effects models were fitted to trajectories of sac diameter, and model-predicted sac diameter and rate of growth were used in prognostic Cox proportional hazards models.ResultsSome 785 patients from the EVAR trials were included, of whom 155 (19·7 per cent) experienced at least one rupture or required a rupture-preventing reintervention during follow-up. An increased risk was associated with preoperative AAA size, rate of sac growth and the number of previously detected complications. A prognostic model using predicted sac growth alone had good discrimination at 2 years (C-index 0·68), 3 years (C-index 0·72) and 5 years (C-index 0·75) after operation and had excellent external validation (C-index 0·76-0·79). More than 5 years after operation, growth rates above 1 mm/year had a sensitivity of over 80 per cent and specificity over 50 per cent in identifying events occurring within 2 years.ConclusionSecondary sac growth is an important predictor of rupture or rupture-preventing reintervention to enable the development of personalized surveillance intervals. A dynamic prognostic model has the potential to tailor surveillance by identifying a large proportion of patients who may require less intensive follow-up.
| S-EPMC6175165 | biostudies-literature
Project description:The aim of this study was to assess the relative gene expression in human AAA and AOD. Genome-wide expression analysis of abdominal aortic aneurysm (AAA) and aortic occlusive disease (AOD) specimens obtained from 20 patients with small AAA (mean maximum aortic diameter=54.3±2.3 mm), 29 patients with large AAA (mean maximum aortic diameter=68.4±14.3 mm), and 9 AOD patients (mean maximum aortic diameter=19.6±2.6 mm). Relative aortic gene expression was compared with that of 10 control aortic specimen of organ donors.
2015-06-30 | E-GEOD-57691 | biostudies-arrayexpress
Project description:IntroductionRuptured abdominal aortic aneurysms (AAAs) are known to be associated with high fatal outcomes. Giant AAAs are often defined as having a maximum diameter over 13 cm. Large AAAs over 8 cm have demonstrated a yearly rupture rate of 30-50%, which explains the rarity of giant AAAs. Endovascular repair of ruptured AAAs (rAAAs) is increasingly advocated because of the shorter hospital stay and fewer post-operative complications. Nonetheless, outcomes regarding mortality and cost-effectiveness show a large variability and long-term outcomes are lacking. Few data have been published on treatment of giant AAAs and rAAAs; however, open surgery is generally the preferred option.ReportAn 83 year old presented to the Emergency Department with a history of ruptured abdominal aortic aneurysm treated with an aorto-uni-iliac endograft and a femorofemoral crossover bypass. During follow up, this was complicated by a symptomatic type III endoleak, which was treated by endovascular repair. During the current admission, he presented with a re-rupture of his former aneurysm, which now was 18 cm diameter because of a type IA endoleak. Open surgical repair was performed and the post-operative course was without complications.DiscussionThe current case underlines the value of vascular surgeons being able to perform both open and endovascular surgery in rAAA.
| S-EPMC6355428 | biostudies-literature
Project description:By modeling interaction of cigarette smoke and hypercholesterolemia, we provide experimental evidence that atherosclerotic disease directly contributes to AAA formation and rupture; AAA progression is mediated by inflammatory Mφ residing within associated atherosclerotic plaque.
2024-09-01 | GSE224587 | GEO
Project description:Atherosclerosis (ATH) and aortic aneurysms (AA) remain challenging chronic diseases that confer high morbidity and mortality despite advances in medical, interventional, and surgical care. RNA interference represents a promising technology that may be utilized to silence genes contributing to ATH and AA. Despite positive results in preclinical and some clinical feasibility studies, challenges such as target/sequence validation, tissue specificity, transfection efficiency, and mitigation of unwanted off-target effects remain to be addressed. In this review the most current targets and some novel approaches in siRNA delivery are being discussed. Due to the plethora of investigated targets, only studies published between 2010 and 2014 were included.
| S-EPMC4295203 | biostudies-literature
Project description:BACKGROUND:Ultrasmall superparamagnetic particles of iron oxide (USPIO) detect cellular inflammation on magnetic resonance imaging (MRI). In patients with abdominal aortic aneurysm, we assessed whether USPIO-enhanced MRI can predict aneurysm growth rates and clinical outcomes. METHODS:In a prospective multicenter open-label cohort study, 342 patients with abdominal aortic aneurysm (diameter ?40 mm) were classified by the presence of USPIO enhancement and were monitored with serial ultrasound and clinical follow-up for ?2 years. The primary end point was the composite of aneurysm rupture or repair. RESULTS:Participants (85% male, 73.1±7.2 years) had a baseline aneurysm diameter of 49.6±7.7 mm, and USPIO enhancement was identified in 146 (42.7%) participants, absent in 191 (55.8%), and indeterminant in 5 (1.5%). During follow-up (1005±280 days), 17 (5.0%) abdominal aortic aneurysm ruptures, 126 (36.8%) abdominal aortic aneurysm repairs, and 48 (14.0%) deaths occurred. Compared with those without uptake, patients with USPIO enhancement have increased rates of aneurysm expansion (3.1±2.5 versus 2.5±2.4 mm/year, P=0.0424), although this was not independent of current smoking habit (P=0.1993). Patients with USPIO enhancement had higher rates of aneurysm rupture or repair (47.3% versus 35.6%; 95% confidence intervals, 1.1-22.2; P=0.0308). This finding was similar for each component of rupture (6.8% versus 3.7%, P=0.1857) or repair (41.8% versus 32.5%, P=0.0782). USPIO enhancement was associated with reduced event-free survival for aneurysm rupture or repair (P=0.0275), all-cause mortality (P=0.0635), and aneurysm-related mortality (P=0.0590). Baseline abdominal aortic aneurysm diameter (P<0.0001) and current smoking habit (P=0.0446) also predicted the primary outcome, and the addition of USPIO enhancement to the multivariate model did not improve event prediction (c-statistic, 0.7935-0.7936). CONCLUSIONS:USPIO-enhanced MRI is a novel approach to the identification of aortic wall cellular inflammation in patients with abdominal aortic aneurysms and predicts the rate of aneurysm growth and clinical outcome. However, it does not provide independent prediction of aneurysm expansion or clinical outcomes in a model incorporating known clinical risk factors. CLINICAL TRIAL REGISTRATION:URL: http://www.isrctn.com. Unique identifier: ISRCTN76413758.
| S-EPMC5571881 | biostudies-literature
Project description:The objective of this work is to develop a robust method for human abdominal aortic aneurysm (AAA) centerline detection that can contribute to the accurate computation of features for the prediction of AAA rupture risk. A semiautomatic algorithm is proposed for detecting the lumen centerline in contrast-enhanced abdominal computed tomography images based on online adaboost classifiers, which does not require prior image segmentation. The algorithm was developed and applied to thirty ruptured and thirty unruptured AAA image data sets and the tortuosities of the detected centerline were measured to assess the correlation between AAA tortuosity and the binary ruptured and unruptured labels. The lumen of each data set was segmented manually by a trained radiologist and the resulting centerlines of each data set were defined as the gold standard to evaluate the accuracy of the algorithm and to compare it against two widely used segmentation techniques. The average mean relative accuracy of the offline adaboost classifier is 91.9% with a standard deviation of 1.6%; for the online adaboost classifier it is 93.6% with a standard deviation of 1.9% (p<0.05). The online adaboost classifier outperforms the offline adaboost classifier while their computational costs are similar. Aneurysm tortuosity computed from an accurately derived lumen centerline using online adaboost is statistically higher for ruptured aneurysms compared to unruptured aneurysms, indicating that tortuosity can be used to assess rupture risk in the vascular clinic.
| S-EPMC3776471 | biostudies-literature