Abdominal aortic aneurysm

Davis, Frank M.; Rateri, Debra L.; Daugherty, Alan

doi:10.1097/hco.0000000000000216

Cited by 133 publications

(61 citation statements)

References 75 publications

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“…These downstream effects were also evident in the present study, thus likely contributing to AAA development (Supplementary Figure S10) 16, 22, 23 . In addition, enhanced vascular ER and oxidative stress further promote immune cell infiltration, which is also critical for AAA development 4 . Therefore, the findings demonstrated in this manuscript suggest that all of these mechanisms are potentially mediated by a single but multifunctional metalloprotease ADAM17 specifically expressed in VSMCs.…”

Section: Discussionmentioning

confidence: 99%

“…Activation of the renin angiotensin II (AngII) system has been implicated in AAA development in human and animal models of AAA 2, 3 . While the detailed molecular mechanism by which AngII promotes AAA development remains unclear, it seems to involve multiple cell types (leukocytes, vascular smooth muscle cells (VSMC) and endothelial cells) and signaling responses such as oxidative stress, induction of inflammatory cytokines and activation of matrix metalloproteinases (MMPs) 4, 5 . However, limited information is available regarding the cell type-specific mechanism critical for AAA development.…”

Section: Introductionmentioning

confidence: 99%

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Vascular ADAM17 (a Disintegrin and Metalloproteinase Domain 17) Is Required for Angiotensin II/β-Aminopropionitrile–Induced Abdominal Aortic Aneurysm

et al. 2017

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Angiotensin II (AngII)-activated epidermal growth factor receptor (EGFR) has been implicated in abdominal aortic aneurysm (AAA) development. In vascular smooth muscle cells (VSMC), AngII activates EGFR via a metalloproteinase, a disintegrin and metallopeptidase domain 17 (ADAM17). We hypothesized that AngII-dependent AAA development would be prevented in mice lacking ADAM17 in VSMCs. To test this concept, control and VSMC ADAM17 deficient mice were co-treated with AngII and a lysyl oxidase inhibitor, β-aminopropionitrile, to induce AAA. We found that 52.4% of control mice did not survive due to aortic rupture. All other surviving control mice developed AAA and demonstrated enhanced expression of ADAM17 in the AAA lesions. In contrast, all AngII and β-aminopropionitrile-treated VSMC ADAM17 deficient mice survived and showed reduction in external/internal diameters (51%/28%, respectively). VSMC ADAM17 deficiency was associated with lack of EGFR activation, interleukin-6 induction, ER/oxidative stress and matrix deposition in the abdominal aorta of treated mice. However, both VSMC ADAM17 deficient and control mice treated with AngII and β-aminopropionitrile developed comparable levels of hypertension. Treatment of C57Bl/6 mice with an ADAM17 inhibitory antibody but not with control IgG also prevented AAA development. In conclusion, VSMC ADAM17 silencing or systemic ADAM17 inhibition appears to protect mice from AAA formation. The mechanism appears to involve suppression of EGFR activation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Vascular ADAM17 (a Disintegrin and Metalloproteinase Domain 17) Is Required for Angiotensin II/β-Aminopropionitrile–Induced Abdominal Aortic Aneurysm

et al. 2017

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“…AF is associated with atrial fibrosis and remodeling. TGF-β signaling plays a critical role in the pathogenesis of AAs and AF [21-23]. Our previous study showed an association of AA with malignancies and Marfan syndrome [24].…”

Section: Discussionmentioning

confidence: 99%

Association between Atrial Fibrillation and Aortic Aneurysms: A Population-Based Cohort Study

et al. 2018

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Objective: Atrial fibrillation (AF) is the most common form of sustained arrhythmia. Several molecular pathways associated with the pathogenesis of AF also participate in the initiation and progression of aortic aneurysm (AA). In this study, we aimed to evaluate potential associations between AA and AF. Patients and Methods: The data for this nationwide population-based retrospective cohort study were obtained from Taiwan’s National Health Insurance Research Database (NHIRD). All medical conditions for each case and the controls were categorized using the 9th revision of the International Classification of Diseases (ICD-9). Odds ratios and 95% confidence intervals for associations between AF and AA were estimated using Cox regression and adjusted for comorbidities. Results: Our analyses included 116,225 AF cases and 116,225 propensity score-matched controls. Compared with the controls, the patients with AF exhibited a significantly increased risk of developing an AA (adjusted hazard ratio, HR 1.243, p < 0.001). Another cohort of 19,776 patients diagnosed with AA were identified, and 19,776 propensity score-matched patients were included as controls. Patients who had AA were also at an increased risk of developing AF (adjusted HR 1.187, p < 0.001). Heart failure (HF) was a common risk factor for both AA and AF. Conclusion: There are associations between AF and AA. HF is a mutual risk factor for the development of AF and AA.

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“…Of the four novel loci, only the association at 20q13.12 maps near a candidate gene with suspected involvement in AAA, MMP9 encoding the matrix metalloproteinase-9. Matrix metalloproteinases are secreted into the intima by atherosclerotic inflammatory processes where they damage the ECM and have been the target of therapeutic strategies both in CAD and AAA 14 . MMP9 protein in particular is found in tissues of advanced AAA and genetic variation in the MMP9 gene has been previously associated with AAA, although not at the statistical significance standards in the current work 15 .…”

mentioning

confidence: 99%