Inflammatory Mediators in Abdominal Aortic Aneurysms

Cassimjee, Ismail; Lee, Regent; Patel, Jyoti

doi:10.5772/65961

Cited by 4 publications

(4 citation statements)

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“…The finding that surgical treatment of AAA (OSR or EVAR) results in an improvement in FMD suggests the aneurysm itself to be a nidus of stimulus causing the deterioration of FMD observed during its natural history. We hypothesise that intraluminal thrombus is the source of such biological signals, as it is present in significant volumes in most AAAs and contains biologically active cells 25,26. This hypothesis requires further investigation.…”

Section: Discussionmentioning

confidence: 93%

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Flow Mediated Dilatation and Progression of Abdominal Aortic Aneurysms

Lee

Bellamkonda

Jones

et al. 2017

European Journal of Vascular and Endovascular Surgery

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Objective/BackgroundBiomarker(s) for prediction of the future progression rate of abdominal aortic aneurysms (AAA) may be useful to stratify the management of individual patients. AAAs are associated with features of systemic inflammation and endothelial dysfunction. Flow mediated dilatation (FMD) of the brachial artery is a recognised non-invasive measurement for endothelial function. We hypothesised that FMD is a potential biomarker of AAA progression and reflects the temporal changes of endothelial function during AAA progression.MethodsIn a prospectively recruited cohort of patients with AAAs (Oxford Abdominal Aortic Aneurysm Study), AAA size was recorded by antero-posterior diameter (APD) (outer to outer) on ultrasound. Annual AAA progression was calculated by (ΔAPD/APD at baseline)/(number of days lapsed/365 days). FMD was assessed at the same time as AAA size measurement. Analyses of data were performed in the overall cohort, and further in subgroups of AAA by size (small: 30–39 mm; moderate: 40–55 mm; large: > 55 mm).ResultsFMD is inversely correlated with the diameter of AAAs in all patients (n = 162, Spearman’s r = −.28, p < .001). FMD is inversely correlated with AAA diameter progression in the future 12 months (Spearman’s r = −.35, p = .001), particularly in the moderate size group. Furthermore, FMD deteriorates during the course of AAA surveillance (from a median of 2.0% at baseline to 1.2% at follow-up; p = .004), while surgical repair of AAAs (n = 50 [open repair n = 22, endovascular repair n = 28)] leads to an improvement in FMD (from 1.1% pre-operatively to 3.8% post-operatively; p < .001), irrespective of the type of surgery.ConclusionFMD is inversely correlated with future AAA progression in humans. FMD deteriorates during the natural history of AAA, and is improved by surgery. The utility of FMD as a potential biomarker in the context of AAA warrants further investigation.

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Section: Discussionmentioning

confidence: 93%

“…We hypothesise that intraluminal thrombus is the source of such biological signals, as it is present in significant volumes in most AAAs and contains biologically active cells. 25 , 26 This hypothesis requires further investigation.…”

Section: Discussionmentioning

confidence: 97%

Flow Mediated Dilatation and Progression of Abdominal Aortic Aneurysms

Lee

Bellamkonda

Jones

et al. 2017

European Journal of Vascular and Endovascular Surgery

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“…14 There is mounting evidence of T-cells being active in AAA ILT and play a role in AAA pathophysiology. 15 Here we describe a novel role of Attractin in human AAA progression which warrants further mechanistic investigations.…”

Section: Discussionmentioning

confidence: 88%

Integrated Plasma and Tissue Proteomics Reveals Attractin Release by Intraluminal Thrombus of Abdominal Aortic Aneurysms and Improves Aneurysm Growth Prediction in Humans

et al. 2020

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Objective: Discovery of novel biomarkers for AAA growth prediction. Background: Novel biomarker of AAA growth is a recognized priority in research. Our prior work implicated intraluminal thrombus (ILT) in AAAs to be a potential source of systemic mediators during AAA progression. Here we applied a mass spectrometry proteomics pipeline to discover novel biomarkers for AAA growth prediction. Methods: Patients were prospectively recruited. Plasma samples were collected at baseline (n ¼ 62). AAA growth was recorded at 12 months. In Experiment 1, plasma samples from the fastest and slowest growth patients (n ¼ 10 each) were compared. In Experiment 2, plasma samples were collected before and at 10-12 weeks after surgery (n ¼ 29). In Experiment 3, paired ILTand omental biopsies were collected intra-operatively during open surgical repair (n ¼ 3). In Experiment 4, tissue secretome was obtained from ex-vivo culture of these paired tissue samples. Samples were subjected to a liquid chromatography tandem mass spectrometry workflow to discover novel biomarkers. Results: We discovered 3 proteins that are: (i) present in ILT; (ii) released by ILT; (iii) reduced in circulation after AAA surgery; (iv) differs between fast and slow growth AAAs. One of these is Attractin. Plasma Attractin correlates significantly with future AAA growth (Spearman r ¼ 0.35, P < 0.005). Using Attractin and AAA diameter as input variables, the area under receiver operating characteristics for predicting no growth and fast growth or AAA at 12 months is 85% and 76%, respectively. Conclusion: We show that ILT of AAAs releases mediators during the natural history of AAA growth. These are novel biomarkers for AAA growth prediction in humans.

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“…The intraluminal thrombus (ILT) within abdominal aortic aneurysms has previously been held as a bystander to the disease (4). However, emerging evidence indicates ILT to be biologically active and contains inflammatory cells within a network of canaliculi (5)(6)(7). In addition to low ILT volume as a feature of likely persistent endoleak (adopted by the Massoni et al), it has also been observed the spatial distribution of ILT predicts the likelihood of T2E after EVAR.…”

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confidence: 99%