MicroRNA-21 Knockout Exacerbates Angiotensin II–Induced Thoracic Aortic Aneurysm and Dissection in Mice With Abnormal Transforming Growth Factor-β–SMAD3 Signaling

Huang, Xintang; Zhang, Yue; Wu, Jia; Chen, Jiuling; Wang, Sihua; Wu, Jie; Ren, Linyun; Zhang, Anchen; Deng, Peng; Wang, Ke; Wu, Chuangyan; Ding, Xiangchao; Ye, Ping; Xia, Jiahong

doi:10.1161/atvbaha.117.310694

Cited by 65 publications

(49 citation statements)

References 72 publications

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“… 130 A recent study discovered that in mice with Smad3 heterozygous background, aortic miR-21 expression was increased by Ang II infusion, and systemic microRNA-21 deletion exacerbated Ang II–induced TAA formation. 131 This study, combined with studies using TGF-β receptor 2 genetically manipulated mice, provides evidence for the importance of TGF-β–mediated mechanisms in the development of TAA.…”

Section: Angiotensin IImentioning

confidence: 73%

Renin-Angiotensin System and Cardiovascular Functions

Mohammadmoradi

Chen

et al. 2018

ATVB

132

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Section: Angiotensin IImentioning

confidence: 73%

Renin-Angiotensin System and Cardiovascular Functions

Mohammadmoradi

Chen

et al. 2018

ATVB

132

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“…Although aortic lesions that arise in the AngII-infused ApoE −/− mouse do not phenocopy human dissections in many regards -they occur in the abdominal, not thoracic, aorta near major branch sites, they occur at the interface between the media and adventitia rather than within the media, they do not result from a connective tissue disorder, and they do not appear to involve focal accumulations of glycosaminoglycans -they nevertheless represent an important model for study. Recent studies have used this model to gain insight into various molecular components of aortic dissection, including lymphocyte adaptor protein deficiency 36 , smooth muscle α-actin deficiency 37 , ciprofloxacin treatment 38 , and transforming growth factor-β-SMAD3 signaling 39,40 .…”

Section: Discussionmentioning

confidence: 99%

Multimodality Imaging-Based Characterization of Regional Material Properties in a Murine Model of Aortic Dissection

Bersi

Santamaría

Marback

et al. 2020

Sci Rep

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chronic infusion of angiotensin-ii in atheroprone (ApoE −/−) mice provides a reproducible model of dissection in the suprarenal abdominal aorta, often with a false lumen and intramural thrombus that thickens the wall. Such lesions exhibit complex morphologies, with different regions characterized by localized changes in wall composition, microstructure, and properties. We sought to quantify the multiaxial mechanical properties of murine dissecting aneurysm samples by combining in vitro extension-distension data with full-field multimodality measurements of wall strain and thickness to inform an inverse material characterization using the virtual fields method. A key advance is the use of a digital volume correlation approach that allows for characterization of properties not only along and around the lesion, but also across its wall. Specifically, deformations are measured at the adventitial surface by tracking motions of a speckle pattern using a custom panoramic digital image correlation technique while deformations throughout the wall and thrombus are inferred from optical coherence tomography. These measurements are registered and combined in 3D to reconstruct the reference geometry and compute the 3D finite strain fields in response to pressurization. Results reveal dramatic regional variations in material stiffness and strain energy, which reflect local changes in constituent area fractions obtained from histology but emphasize the complexity of lesion morphology and damage within the dissected wall. This is the first point-wise biomechanical characterization of such complex, heterogeneous arterial segments. Because matrix remodeling is critical to the formation and growth of these lesions, we submit that quantification of regional material properties will increase the understanding of pathological mechanical mechanisms underlying aortic dissection.

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“…This protocol is applicable to most mouse models of thoracic aortic aneurysms because they exhibit luminal dilation predominantly in the aortic root to the ascending aorta. This includes chronic angiotensin II infusion that causes aneurysm formation in the ascending aorta of mice 18,19,20,21,22,23 . Mouse models of Marfan syndrome (fibrillin 1 C1041G/+ and fibrillin 1 mgR/mgR mice) display both aortic root and ascending aortic dilation 23,24,25 .…”

Section: Discussionmentioning

confidence: 99%

Ultrasound Imaging of the Thoracic and Abdominal Aorta in Mice to Determine Aneurysm Dimensions

Sawada

Chen

Wright

et al. 2019

JoVE

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Contemporary high-resolution ultrasound instruments have sufficient resolution to facilitate the measurement of mouse aortas. These instruments have been widely used to measure aortic dimensions in mouse models of aortic aneurysms. Aortic aneurysms are defined as permanent dilations of the aorta, which occur most frequently in the ascending and abdominal regions. Sequential measurements of aortic dimensions by ultrasound are the principal approach for assessing the development and progression of aortic aneurysms in vivo. Although many reported studies used ultrasound imaging to measure aortic diameters as a primary endpoint, there are confounding factors, such as probe position and cardiac cycle, that may impact the accuracy of data acquisition, analysis, and interpretation. The purpose of this protocol is to provide a practical guide on the use of ultrasound to measure the aortic diameter in a reliable and reproducible manner. This protocol introduces the preparation of mice and instruments, the acquisition of appropriate ultrasound images, and data analysis.

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MicroRNA-21 Knockout Exacerbates Angiotensin II–Induced Thoracic Aortic Aneurysm and Dissection in Mice With Abnormal Transforming Growth Factor-β–SMAD3 Signaling

Abstract: Our study demonstrated that knockout exacerbated AngII-induced TAAD formation in mice, which was associated with TGF-β signaling dysfunction. Therapeutic strategies targeting TAAD should consider unexpected side effects associated with alterations in TGF-β signaling.

Cited by 65 publications

References 72 publications

Renin-Angiotensin System and Cardiovascular Functions

Renin-Angiotensin System and Cardiovascular Functions

Multimodality Imaging-Based Characterization of Regional Material Properties in a Murine Model of Aortic Dissection

Ultrasound Imaging of the Thoracic and Abdominal Aorta in Mice to Determine Aneurysm Dimensions

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