Gene Expression Profiling in Abdominal Aortic Aneurysms After Finite Element Rupture Risk Assessment

Erhart, Philipp; Schiele, Sandra; Ginsbach, Philip; Grond‐Ginsbach, Caspar; Hakimi, Maani; Böckler, Dittmar; Bermejo, Justo Lorenzo; Dihlmann, Susanne

doi:10.1177/1526602817729165

Cited by 7 publications

(8 citation statements)

References 19 publications

(18 reference statements)

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“…Using FE-A, our group has previously analyzed whether histological features of AAA correlate with predicted rupture risk and clinical parameters of AAA patients (25,26). To investigate, whether the intramural immune response analyzed in the present study may be reflected by any diagnostic marker that is clinically used for AAA disease control, different parameters were tested for association.…”

Section: Resultsmentioning

confidence: 99%

Inflammasome activity in leucocytes decreases with abdominal aortic aneurysm progression

et al. 2019

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Abdominal aortic aneurysms (AAAs) are characterized by chronic inflammatory cell infiltration. The present extended immunohistochemistry study aimed to characterize inflammation in AAA and aortic control samples. In specific, the composition of the infiltrating immune cells and the expression of five inflammasome components in these immune cells were evaluated, in order to characterize their role in AAA development. A total of 104 biopsies from 48 AAA patients and 40 healthy specimens from organ donors were evaluated for their grade of inflammation. Infiltrating leukocytes were characterized by specific markers (CD3, CD20 and CD68), intramural localization and inflammasome protein expression [NLR family pyrin domain containing 3 (NLRP3), absent in melanoma 2 (AIM2), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), Caspase-1 and Caspase-5]. Macrophages, B and T lymphocytes were detected to a similar extent in grade 1, 2 and 3 AAA specimens, whereas in control samples, B and T lymphocytes were rarely observed in grade 1 lesions. Expression frequencies of NLRP3, AIM2 and Caspase-5 were significantly higher in grade 1 lesions of AAA samples compared with grade 1 lesions in control samples. Finally, AIM2, ASC, and Caspase-5 displayed significantly lower expression frequencies in grade 3 compared with grade 2 AAA specimens, and all inflammasome components were less frequently detected in grade 3 than in grade 1 lesions of AAA. This indicates that inflammasome activities decrease with AAA progression in infiltrating leukocytes. No statistically significant association was found for grade 2 and grade 3 lesions and total leukocyte count, C-reactive protein levels, maximal aortic diameter, plasma cholesterol level or biomechanical parameters (derived from finite element analysis) of the respective patients. Overall, the aortic wall of AAA contained lymphocytes and macrophages with different states of activity. The present data suggested that therapeutic inhibition of specific inflammasome components might counteract AAA development and progression.

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Section: Resultsmentioning

confidence: 99%

Inflammasome activity in leucocytes decreases with abdominal aortic aneurysm progression

et al. 2019

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“…We need better solutions for risk stratification of AAA patients. The key to stratification is likely a combination of biomechanical (wall stress, tissue microstructure) and biochemical surrogate markers (e.g., blood markers, metabolic activity, gene expression) [ 96 , 108 ], together with other risk variables (e.g., sex, smoking habits, underlying conditions). Artificial intelligence (AI) is revolutionizing healthcare.…”

Section: Looking Forwardmentioning

confidence: 99%

Predictors of Abdominal Aortic Aneurysm Risks

2020

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Computational biomechanics via finite element analysis (FEA) has long promised a means of assessing patient-specific abdominal aortic aneurysm (AAA) rupture risk with greater efficacy than current clinically used size-based criteria. The pursuit stems from the notion that AAA rupture occurs when wall stress exceeds wall strength. Quantification of peak (maximum) wall stress (PWS) has been at the cornerstone of this research, with numerous studies having demonstrated that PWS better differentiates ruptured AAAs from non-ruptured AAAs. In contrast to wall stress models, which have become progressively more sophisticated, there has been relatively little progress in estimating patient-specific wall strength. This is because wall strength cannot be inferred non-invasively, and measurements from excised patient tissues show a large spectrum of wall strength values. In this review, we highlight studies that investigated the relationship between biomechanics and AAA rupture risk. We conclude that combining wall stress and wall strength approximations should provide better estimations of AAA rupture risk. However, before personalized biomechanical AAA risk assessment can become a reality, better methods for estimating patient-specific wall properties or surrogate markers of aortic wall degradation are needed. Artificial intelligence methods can be key in stratifying patients, leading to personalized AAA risk assessment.

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“…An intriguing concept of biomechanical-biological interactions in AAA was that of segmental aortic stiffening increasing the axial tensile stress in adjacent, compliant, segments causing increased inflammation and proteolysis, which also correlated with age-related changes in the human aorta (281). Investigations into associations between gene expression and wall stress or the estimated ratio between wall stress and wall strength have pointed to differences in expression of lamin A/C and genes related to ECM and cytokine signaling, while strong associations surviving correction for multiple testing are difficult to obtain (228,229,282). On the protein/structural/cellular level, high ratio between wall stress and wall strength was associated with decreased vSMCs and elastic fibers as well as more cholesterol and calcified plaques, whereas increased wall stress was associated with increased collagen 1, III and total collagen (283).…”

Section: Biomechanics Of the Normal Aorta And Abdominal Aortic Aneurysmmentioning

confidence: 99%

“…The RNA from a blood sample of a patient with AAA differs significantly from that of healthy controls, with increased expression of genes related to apoptosis, immunity and proteolysis, but also differs from blood taken from patients with carotid artery stenosis (225,226). One study examined the association between global gene expression and a signal on positron emission tomography (PET) CT, whereas others have compared regions of high and low biomechanical wall stress or rupture risk (227)(228)(229).…”

Section: Transcriptomicsmentioning

confidence: 99%

Neutrophil Elastase-Derived Fibrin Degradation Products Indicate Presence of Abdominal Aortic Aneurysms and Correlate with Intraluminal Thrombus Volume

et al. 2018

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Gene Expression Profiling in Abdominal Aortic Aneurysms After Finite Element Rupture Risk Assessment

Cited by 7 publications

References 19 publications

Inflammasome activity in leucocytes decreases with abdominal aortic aneurysm progression

Inflammasome activity in leucocytes decreases with abdominal aortic aneurysm progression

Predictors of Abdominal Aortic Aneurysm Risks

Neutrophil Elastase-Derived Fibrin Degradation Products Indicate Presence of Abdominal Aortic Aneurysms and Correlate with Intraluminal Thrombus Volume

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