Complement Factor C5a Is Increased in Blood of Patients with Abdominal Aortic Aneurysm and Has Prognostic Potential for Aneurysm Growth.
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ABSTRACT:
SUBMITTER: Zagrapan B
PROVIDER: S-EPMC8397625 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The biomechanics-based Abdominal Aortic Aneurysm (AAA) rupture risk assessment has gained considerable scientific and clinical momentum. However, such studies have mainly focused on information at a single time point, and little is known about how AAA properties change over time. Consequently, the present study explored how geometry, wall stress-related and blood flow-related biomechanical properties change during AAA expansion. Four patients with a total of 23 Computed Tomography-Angiography (CT-A) scans at different time points were analyzed. At each time point, patient-specific properties were extracted from (i) the reconstructed geometry, (ii) the computed wall stress at Mean Arterial Pressure (MAP), and (iii) the computed blood flow velocity at standardized inflow and outflow conditions. Testing correlations between these parameters identified several nonintuitive dependencies. Most interestingly, the Peak Wall Rupture Index (PWRI) and the maximum Wall Shear Stress (WSS) independently predicted AAA volume growth. Similarly, Intra-luminal Thrombus (ILT) volume growth depended on both the maximum WSS and the ILT volume itself. In addition, ILT volume, ILT volume growth, and maximum ILT layer thickness correlated with PWRI as well as AAA volume growth. Consequently, a large ILT volume as well as fast increase of ILT volume over time may be a risk factor for AAA rupture. However, tailored clinical studies would be required to test this hypothesis and to clarify whether monitoring ILT development has any clinical benefit.
| S-EPMC5675455 | biostudies-literature
Project description:Variable imaging methods may add important information about abdominal aortic aneurysm (AAA) progression. The aim of this study is to assess available literature data regarding the predictive imaging factors of AAA growth. This systematic review was conducted using the PRISMA guidelines. A review of the literature was conducted, using PubMed, EMBASE and CENTRAL databases. The quality of the studies was assessed using the Newcastle-Ottawa Scale. Primary outcomes were defined as AAA growth rate and factors associated to sac expansion. The analysis included 23 studies. All patients (2244; mean age; 69.8 years, males; 85%) underwent imaging with different modalities; the initial evaluation was followed by one or more studies to assess aortic expansion. AAA initial diameter was reported in 13 studies (range 19.9-50.9 mm). Mean follow-up was 34.5 months. AAA diameter at the end was ranging between 20.3 and 55 mm. The initial diameter and intraluminal thrombus were characterized as prognostic factors associated to aneurysm expansion. A negative association between atherosclerosis and AAA expansion was documented. Aneurysm diameter is the most studied factor to be associated with expansion and the main indication for intervention. Appropriate diagnostic modalities may account for different anatomical characteristics and identify aneurysms with rapid growth and higher rupture risk. Future perspectives, including computed mathematical models that will assess wall stress and elasticity and further flow characteristics, may offer valuable alternatives in AAA growth prediction.
| S-EPMC8124923 | biostudies-literature
Project description:Abdominal aortic aneurysm is a common pathology in the aging population of the developed world which carries a significant mortality in excess of 80% in case of rupture. Aneurysmal disease probably represents the only surgical condition in which size is such a critical determinant of the need for intervention and therefore the ability to accurately and reproducibly record aneurysm size and growth over time is of outmost importance. In the same time that imaging techniques may be limited by intra- and inter-observer variability and there may be inconsistencies due to different modalities [ultrasound, computed tomography (CT)], rapid technologic advancement have taken aortic imaging to the next level. Digital imaging, multi-detector scanners, thin slice CT and most- importantly the ability to perform 3-dimensional reconstruction and image post-processing have currently become widely available rendering most of the imaging modalities used in the past out of date. The aim of the current article is to report on various imaging methods and current state of the art techniques used to record aneurysm size and growth. Moreover we aim to emphasize on the future research directions and report on techniques which probably will be widely used and incorporated in clinical practice in the near future.
| S-EPMC4770177 | biostudies-literature
Project description:Abdominal aortic aneurysm (AAA) is associated with high morbidity and mortality and is an established cause of unbalanced hemostasis. A number of hemostatic biomarkers have been associated with AAA; however, the utility of hemostatic biomarkers in AAA diagnosis and prognosis is unclear. The aim of the present study was to characterize the potential prognostic value of D-dimer and markers of altered hemostasis in a large cohort of patients with AAAs characterized by either fast or slow aneurysm growth (frequency matched for baseline diameter) and subaneurysmal dilations. We measured plasma concentrations of thrombin-antithrombin (TAT) complex, platelet factor 4 (PF4), and D-dimer in 352 patients with either fast-growing AAAs (>2 mm/y), slow-growing AAAs (<2 mm/y), subaneurysmal aortic dilations, or nonaneurysmal aortas. Plasma D-dimer and TAT were significantly elevated in both AAA and subaneurysmal dilation patients compared with controls. Individuals with D-dimer levels ?500 ng/mL had 3.09 times the odds of subaneurysms, 6.23 times the odds of slow-growing AAAs, and 7.19 times the odds of fast-growing AAAs than individuals with D-dimer level <500 ng/mL. However, no differences in D-dimer concentration were noted between fast- and slow-growing aneurysms. Plasma D-dimer and TAT were strong independent predictors of AAA growth rate with multivariate analysis revealing a 500-ng/mL increase in D-dimer or 1-µg/mL increase in TAT led to additional 0.21-mm and 0.24-mm changes in aortic diameter per year, respectively. Rising levels of plasma TAT, in addition to D-dimer, may predict disease progression and aneurysm growth in patients with AAA or subaneurysmal dilation.
| S-EPMC6258923 | biostudies-literature
Project description:BackgroundThe Asp358Ala variant (rs2228145; A>C) in the IL (interleukin)-6 receptor ( IL6R) gene has been implicated in the development of abdominal aortic aneurysms (AAAs), but its effect on AAA growth over time is not known. We aimed to investigate the clinical association between the IL6R-Asp358Ala variant and AAA growth and to assess the effect of blocking the IL-6 signaling pathway in mouse models of aortic aneurysm rupture or dissection.MethodsUsing data from 2863 participants with AAA from 9 prospective cohorts, age- and sex-adjusted mixed-effects linear regression models were used to estimate the association between the IL6R-Asp358Ala variant and annual change in AAA diameter (mm/y). In a series of complementary randomized trials in mice, the effect of blocking the IL-6 signaling pathways was assessed on plasma biomarkers, systolic blood pressure, aneurysm diameter, and time to aortic rupture and death.ResultsAfter adjusting for age and sex, baseline aneurysm size was 0.55 mm (95% CI, 0.13-0.98 mm) smaller per copy of the minor allele [C] of the Asp358Ala variant. Change in AAA growth was -0.06 mm per year (-0.18 to 0.06) per copy of the minor allele; a result that was not statistically significant. Although all available worldwide data were used, the genetic analyses were not powered for an effect size as small as that observed. In 2 mouse models of AAA, selective blockage of the IL-6 trans-signaling pathway, but not combined blockage of both, the classical and trans-signaling pathways, was associated with improved survival ( P<0.05).ConclusionsOur proof-of-principle data are compatible with the concept that IL-6 trans-signaling is relevant to AAA growth, encouraging larger-scale evaluation of this hypothesis.
| S-EPMC6383754 | biostudies-literature
Project description:Abdominal aortic aneurysm represents a distinct group of vascular lesions, in terms of surveillance and treatment. Screening and follow-up of patients via duplex ultrasound has been well established and proposed by current guidelines. However, serum circulating biomarkers could earn a position in individualized patient surveillance, especially in cases of aggressive AAA growth rates. A systematic review was conducted to assess the correlation of AAA expansion rates with serum circulating biomarkers. A data search of English medical literature was conducted, using PubMed, EMBASE, and CENTRAL, until 7 March 2021, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement (PRISMA) guidelines. Studies reporting on humans, on abdominal aortic aneurysm growth rates and on serum circulating biomarkers were included. No statistical analysis was conducted. A total of 25 studies with 4753 patients were included. Studies were divided in two broad categories: Those reporting on clinically applicable (8 studies) and those reporting on experimental (17 studies) biomarkers. Twenty-three out of 25 studies used duplex ultrasound (DUS) for following patients. Amongst clinically applicable biomarkers, D-dimers, LDL-C, HDL-C, TC, ApoB, and HbA1c were found to bear the most significant association with AAA growth rates. In terms of the experimental biomarkers, PIIINP, osteopontin, tPA, osteopontin, haptoglobin polymorphisms, insulin-like growth factor I, thioredoxin, neutrophil extracellular traps (NETs), and genetic factors, as polymorphisms and microRNAs were positively correlated with increased AAA expansion rates. In the presence of future robust data, specific serum biomarkers could potentially form the basis of an individualized surveillance strategy of patients presenting with increased AAA growth rates.
| S-EPMC8072679 | biostudies-literature
Project description:Abdominal aortic aneurysm (AAA) is a common vascular disease associated with high mortality rate due to progressive enlargement and eventual rupture. There is currently no established therapy known to alter the rate of aneurysmal expansion. Thus, understanding the processes that initiate and sustain aneurysmal growth is pivotal for the development of medical therapies aimed at halting disease progression. Using an elastase-induced AAA mouse model that recapitulates key features of human AAA, we previously reported that a natural IgG antibody directs alternative pathway complement activation and initiates the inflammatory process that culminates in aneurysmal development. The target of this natural antibody, however, was unknown. Herein we identify a natural IgG that binds to fibrinogen deposited in elastase-perfused aortic tissues, activates the complement lectin pathway (LP), and induces AAA. Moreover, we establish that alterations in the glycosylation patterns of this antibody critically affect its ability to activate the LP in vivo. We find that LP activation precedes the alternative pathway and absence of the LP complement protein mannan-binding lectin abrogates elastase-induced AAA. In human AAA tissues the mouse anti-fibrinogen antibody recognizes epitopes that localize to the same areas that stain positively for mannan-binding lectin, which suggests that the complement LP is engaged in humans as well. Lastly, we demonstrate that circulating antibodies in a subset of AAA patients react against fibrinogen or fibrinogen-associated epitopes in human aneurysmal tissues. Our findings support the concept that an autoimmune process directed at aortic wall self-antigens may play a central role in the immunopathogenesis of AAA.
| S-EPMC3831981 | biostudies-literature
Project description:Abdominal aortic aneurysm (AAA) is a multifactorial disease with a strong genetic component. Since the first candidate gene studies were published 20 years ago, approximately 100 genetic association studies using single nucleotide polymorphisms (SNPs) in biologically relevant genes have been reported on AAA. These studies investigated SNPs in genes of the extracellular matrix, the cardiovascular system, the immune system, and signaling pathways. Very few studies were large enough to draw firm conclusions and very few results could be replicated in another sample set. The more recent unbiased approaches are family-based DNA linkage studies and genome-wide genetic association studies, which have the potential of identifying the genetic basis for AAA, only when appropriately powered and well-characterized large AAA cohorts are used. SNPs associated with AAA have already been identified in these large multicenter studies. One significant association was of a variant in a gene called contactin-3, which is located on chromosome 3p12.3. However, two follow-up studies could not replicate this association. Two other SNPs, which are located on chromosome 9p21 and 9q33, were replicated in other samples. The two genes with the strongest supporting evidence of contribution to the genetic risk for AAA are the CDKN2BAS gene, also known as ANRIL, which encodes an antisense ribonucleic acid that regulates expression of the cyclin-dependent kinase inhibitors CDKN2A and CDKN2B, and DAB2IP, which encodes an inhibitor of cell growth and survival. Functional studies are now needed to establish the mechanisms by which these genes contribute toward AAA pathogenesis.
| S-EPMC3058859 | biostudies-literature
Project description:BackgroundAbdominal aortic aneurysms (AAAs) represent a complex multifactorial hemodynamic, thrombotic, and inflammatory process that can ultimately result in aortic rupture and death. Despite improved screening and surgical management of AAAs, the mortality rates have remained high after rupture, and little progress has occurred in the development of nonoperative treatments. Intraluminal thrombus (ILT) is present in most AAAs and might be involved in AAA pathogenesis. The present review examined the latest clinical and experimental evidence for possible involvement of the ILT in AAA growth and rupture.MethodsA literature review was performed after a search of the PubMed database from 2012 to June 2020 using the terms "abdominal aortic aneurysm" and "intraluminal thrombus."ResultsThe structure, composition, and hemodynamics of ILT formation and propagation were reviewed in relation to the hemostatic and proteolytic factors favoring ILT deposition. The potential effects of the ILT on AAA wall degeneration and rupture, including a review of the current controversies regarding the position, thickness, and composition of ILT, are presented. Although initially potentially protective against increased wall stress, increasing evidence has shown that an increased volume and greater age of the ILT have direct detrimental effects on aortic wall integrity, which might predispose to an increased rupture risk.ConclusionsILT does not appear to be an innocent bystander in AAA pathophysiology. However, its exact role remains elusive and controversial. Despite computational evidence of a possible protective role of the ILT in reducing wall stress, increasing evidence has shown that the ILT promotes AAA wall degeneration in humans and in animal models. Further research, with large animal models and with more chronic ILT is crucial for a better understanding of the role of the ILT in AAAs and for the potential development of targeted therapies to slow or halt AAA progression.
| S-EPMC8489244 | biostudies-literature
Project description:BackgroundRed blood cell (RBC) transfusions are associated with increased mortality and morbidity. The aim of this analysis was to examine the association between RBC transfusions and long-term survival for patients undergoing elective open infrarenal abdominal aortic aneurysm (AAA) repair with up to 15 years of follow-up.MethodsProspective cohort study using data from The Danish Vascular Registry from 2000-2015. Primary endpoint was all-cause mortality. Secondary endpoints were in-hospital complications. Transfused patients were divided into subgroups based on received RBC transfusions (1, 2-3, 4-5 or > 5). Using Cox regression multi-adjusted analysis, non-transfused patients were compared to transfused patients (1, 2-3, 4-5, >5 transfusions) for both primary and secondary endpoints.ResultsThere were 3 876 patients included with a mean survival of 9.1 years. There were 801 patients who did not receive transfusions. Overall 30-day mortality was 3.1% (121 patients) and 3.6% (112) for all transfused patients. For the five subgroups 30-day mortality was: No transfusions 1.1% (9 patients), 1 RBC 1.2% (4 patients), 2-3 RBC 2.2% (26 patients), 4-5 RBC 1.9% (14 patients) and > 5 RBC 7.9% (68 patients). After receiving RBCs, the hazard ratio for death was 1.54 (95% CI 1.27-1.85) compared to non-transfused patients. There was a significant increase in mortality when receiving 2-3 RBC: HR 1.32 (95% CI 1.07-1.62), 4-5 RBC: 1.64 (1.32-2.03) and >5 RBC: 1.96 (1.27-1.85) in a multi-adjusted model.ConclusionThere is a dose-dependent association between RBC transfusions received during elective AAA repair and an increase in short- and long-term mortality. Approximately 25% of included patients had preoperative anemia. These findings should raise awareness regarding potentially unnecessary and harmful RBC transfusions.
| S-EPMC6623955 | biostudies-literature