Spatiotemporal mapping of matrix remodelling and evidence of<i>in situ</i>elastogenesis in experimental abdominal aortic aneurysms

Deb, Partha; Ramamurthi, Anand

doi:10.1002/term.1905

Cited by 13 publications

(6 citation statements)

References 31 publications

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“…As aortic inflammation progresses gradually, aneurysmal tissue repair process may be initiated. Our results are consistent with previous studies in PPE-induced rat AAA models [31]. Our data suggest that day 14 after PPE infusion in mice is an important time point for histologically studying AAA pathogenesis and evaluating therapeutic efficacy.…”

Section: Discussionsupporting

confidence: 92%

“…While experimental AAAs can be induced in several rodents for biomedical and therapeutical studies, the mouse is the most popular used species [12,26,27,29,30]. A previous study, which focuses on spatiotemporal matrix remodeling, pointed out that aortic expansion was slower between 14 and 21 days than earlier, suggesting autostabilization of the AAA in rats [31]. However, no published data are available for time-course for aortic histopathologies in elastase-induced mouse experimental AAAs.…”

Section: Discussionmentioning

confidence: 99%

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Temporal and Quantitative Analysis of Aortic Immunopathologies in Elastase-Induced Mouse Abdominal Aortic Aneurysms

Tian

Chen

Liu

et al. 2021

Journal of Immunology Research

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Objective. Elastase-induced abdominal aortic aneurysm (AAA) model is widely used for aneurysmal pathogenesis and translational research. However, temporal alternations in aneurysmal histologies remain unknown. This study is aimed at analyzing temporal immunopathologies of aneurysmal aorta following experimental AAA induction. Methods. Male C57BL/6J mice at the age of 10-14 weeks received intra-aortic infusion of elastase to induce AAAs. Aortic diameters at the baseline and indicated days after AAA induction were measured, and aortae were collected for histopathological analysis. Results. Aorta diameters increased from 0.52 mm at the baseline levels to 0.99 mm, 1.34 mm, and 1.41 mm at days 7, 14, and 28, respectively, corresponding 90%, 158%, and 171% increases over the baseline level. Average aortic diameters did not differ between days 14 and 28. Severe elastin degradation and smooth muscle cell depletion were found at days 14 and 28 as compared to the baseline and day 7. No difference in the scores of medial elastin and SMC destruction was noted between days 14 and 28. Consistent results were found for leukocyte accumulation, neoangiogenesis, and matrix metalloproteinase expression. Twenty-eight days after AAA induction, all aneurysmal pathologies showed an attenuated trend, although most histopathological parameters did no differ between days 14 and 28. Conclusion. Our data suggest that almost aneurysmal immunohistopathologies reach maximal 14 days following AAA induction. Analysis of day 14 histologies is sufficient for AAA pathogenesis and translational studies in elastase-induced mouse experimental AAAs.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Temporal and Quantitative Analysis of Aortic Immunopathologies in Elastase-Induced Mouse Abdominal Aortic Aneurysms

Tian

Chen

Liu

et al. 2021

Journal of Immunology Research

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“…Elastin and SMCs are the main functional components of the vascular media. PPE infusion severely degrades elastin and causes SMC apoptosis leading to media SMCs depletion [25,39]. In PPE infusion model, aortic leukocytes produce inflammatory cytokines, which may promote SMC apoptosis or dedifferentiation and show less alpha-actin positive staining.…”

Section: Discussionmentioning

confidence: 99%

Dapagliflozin Ameliorates the Formation and Progression of Experimental Abdominal Aortic Aneurysms by Reducing Aortic Inflammation in Mice

Liu

Wei

et al. 2022

Oxidative Medicine and Cellular Longevity

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Background. Dapagliflozin, a sodium glucose transporter protein-2 (SGLT-2) inhibitor, reduces the risk for cardiovascular diseases. However, the influence of dapagliflozin on nondissecting abdominal aortic aneurysms (AAAs) remains unclear. Methods. AAAs were created in male C57BL/6 mice via intra-aortic porcine pancreatic elastase (PPE) infusion. Mice were daily treated with dapagliflozin (1 or 5 mg/kg body weight) or an equal volume of vehicle through oral gavage beginning one day prior to PPE infusion for 14 days. To investigate its translational value, dapagliflozin or vehicle was also administered to mice with existing AAAs in another cohort. Aortic diameters were measured prior to (day 0 for baseline) and 14 days after PPE infusion. After sacrifice, mice aortae were collected, and following histological analyses were performed. Results. Dapagliflozin treatment significantly reduced aneurysmal aortic expansion following PPE infusion as compared to vehicle treatment especially at 5 mg/kg body weight (approximately 21% and 33% decreases in 1 and 5 mg/kg treatment groups, respectively). The dose-dependent attenuation of AAAs by dapagliflozin was also confirmed on histological analyses. Dapagliflozin remarkably reduced aortic accumulation of macrophages, CD4+ T cells, and B cells particularly following dapagliflozin treatment at 5 mg/kg. Dapagliflozin treatment also markedly attenuated medial SMC loss. Though the difference was not significant, dapagliflozin treatment tended to attenuate CD8+ T cells and elastin degradation. Dapagliflozin treatment at 5 mg/kg caused a 53% reduction in neovessel density. Furthermore, dapagliflozin treatment mitigated further progress of existing AAAs. Conclusion. Dapagliflozin treatment ameliorated PPE-induced AAAs by inhibiting aortic leukocytes infiltration and angiogenesis.

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“…For instance, in lung fibrosis the abnormal accumulation of collagen results in a stiffer ECM [ 32 , 51 , 52 ] and hence less compliant lungs, whereas in lung emphysema the cause of increased pulmonary compliance is an abnormal augmentation in the separation of alveolar septa caused by parenchymal tissue destruction [ 44 , 53 ]. It could be postulated that the fibrillin-1 mutation in our experimental mice model results in the alteration of the lung ECM because this glycoprotein is a microfibril constituent that plays a role as a scaffold for tropoelastin and, therefore in elastic fiber formation and organization [ 54 ]. However, we did not find alterations in the nanomechanics of Marfan mice lungs.…”

Section: Discussionmentioning

confidence: 99%

Early Impairment of Lung Mechanics in a Murine Model of Marfan Syndrome

et al. 2016

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Early morbidity and mortality in patients with Marfan syndrome (MFS) -a connective tissue disease caused by mutations in fibrillin-1 gene- are mainly caused by aorta aneurysm and rupture. However, the increase in the life expectancy of MFS patients recently achieved by reparatory surgery promotes clinical manifestations in other organs. Although some studies have reported respiratory alterations in MFS, our knowledge of how this connective tissue disease modifies lung mechanics is scarce. Hence, we assessed whether the stiffness of the whole lung and of its extracellular matrix (ECM) is affected in a well-characterized MFS mouse model (FBN1C1039G/+). The stiffness of the whole lung and of its ECM were measured by conventional mechanical ventilation and atomic force microscopy, respectively. We studied 5-week and 9-month old mice, whose ages are representative of early and late stages of the disease. At both ages, the lungs of MFS mice were significantly more compliant than in wild type (WT) mice. By contrast, no significant differences were found in local lung ECM stiffness. Moreover, histopathological lung evaluation showed a clear emphysematous-like pattern in MFS mice since alveolar space enlargement was significantly increased compared with WT mice. These data suggest that the mechanism explaining the increased lung compliance in MFS is not a direct consequence of reduced ECM stiffness, but an emphysema-like alteration in the 3D structural organization of the lung. Since lung alterations in MFS are almost fully manifested at an early age, it is suggested that respiratory monitoring could provide early biomarkers for diagnosis and/or follow-up of patients with the Marfan syndrome.

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Spatiotemporal mapping of matrix remodelling and evidence ofin situelastogenesis in experimental abdominal aortic aneurysms

Cited by 13 publications

References 31 publications

Temporal and Quantitative Analysis of Aortic Immunopathologies in Elastase-Induced Mouse Abdominal Aortic Aneurysms

Temporal and Quantitative Analysis of Aortic Immunopathologies in Elastase-Induced Mouse Abdominal Aortic Aneurysms

Dapagliflozin Ameliorates the Formation and Progression of Experimental Abdominal Aortic Aneurysms by Reducing Aortic Inflammation in Mice

Early Impairment of Lung Mechanics in a Murine Model of Marfan Syndrome

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