Induction of thoracic aortic dissection: a mini-review of β-aminopropionitrile-related mouse models

Zheng, Haiqiong; Rong, Jiabing; Ye, Feiming; Xu, Yinchuan; Lü, Hong; Wang, Jianan

doi:10.1631/jzus.b2000022

Cited by 28 publications

(24 citation statements)

References 59 publications

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“…It has been known since the 1950s that BAPN can compromise the structural integrity of the aorta, though with a strong dependence on the age at exposure; younger rodents are more vulnerable than older rodents. Most recent studies in mice have given BAPN either to young animals (often starting at weaning, that is, 3 weeks of age) or in combination with induced hypertension in older animals (often 8 weeks of age or older) 31,32 . Given that BAPN only affects newly synthesized fibers, these protocols have proven useful because extracellular matrix turnover is high during aortic development 33 and hypertension accelerates matrix turnover in the aorta in adults 34 .…”

Section: Discussionmentioning

confidence: 99%

“…Littermate Fbn1 +/+ (wild-type control, WT) and Fbn1 C1041G/+ (Marfan syndrome, MFS) mice were maintained on normal chow and water up to the time of experimental study. To prevent cross-linking of newly synthesized elastic or collagen fibers, female and male WT (FWT, MWT) and female and male MFS (FMFS, MMFS) mice were given β-aminopropionitrile (BAPN; Sigma Aldrich A3134) ad libitum at 2000 mg/l in the drinking water for 4 weeks 31 beginning either at 4 (P28) or 8 (P56) weeks of age. Hence, vessels were excised for testing at either 8 or 12 weeks of age, without or with 4-weeks of BAPN exposure, thus resulting in 16 primary Groups to be compared histo-mechanically.…”

Section: Methodsmentioning

confidence: 99%

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Compensatory aortic remodeling in Marfan syndrome protects against sexually dimorphic rupture during a BAPN challenge

Weiss

Rego

Cavinato

et al. 2022

Preprint

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Transmural rupture of the aorta is responsible for significant morbidity and mortality; it occurs when wall stress exceeds local wall strength. Amongst other conditions, the aortic root and ascending aorta become vulnerable to dissection and rupture in Marfan syndrome, a connective tissue disorder that results in a progressive fragmentation and degradation of the elastic fibers of the aortic wall. Whereas competent elastic fibers are critical for aortic functionality, cross-linked collagen fibers endow the aorta with its stiffness and strength. In this paper, we contrast progressive degeneration of the ascending aorta in male and female Marfan and wild-type mice, with and without chronic exposure to a potent inhibitor of lysyl oxidase (β-aminopropionitrile, or BAPN), to examine effects of extracellular matrix cross-linking in aortic dilatation and rupture. We found a strong sexual dimorphism in aortic dilatation in Marfan mice and aortic rupture in wild-type mice, but also a compensatory remodeling of the aorta that protected the Marfan aorta against lethal rupture despite a strong BAPN challenge. This compensation appears to be mediated via increased lysyl oxidase in the female and especially male Marfan aorta, resulting in improved collagen fiber stability and integrity, particularly of fibril bundles in the adventitia.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Compensatory aortic remodeling in Marfan syndrome protects against sexually dimorphic rupture during a BAPN challenge

Weiss

Rego

Cavinato

et al. 2022

Preprint

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“…In this study, to avoid affecting the survival rate while further increasing the rate of aneurysm formation, two methods of adding calcium chloride and beta aminopropionitrile to elastase perfusion were investigated separately. Calcium chloride ( 18 ) induced the inflammatory reaction of the arterial wall, while beta aminopropionitrile ( 19 ) inhibited the cross-linking process of collagen and elastin to construct an AAA animal model. Using these two methods alone has the disadvantage of a low aneurysm formation rate.…”

Section: Discussionmentioning

confidence: 99%

Establishment of a New Abdominal Aortic Aneurysm Model in Rats by a Retroperitoneal Approach

Zhu

Tang

Zhou

et al. 2022

Front. Cardiovasc. Med.

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BackgroundConstructing an ideal model of abdominal aortic aneurysm (AAA) is of great significance to elucidate its complex pathogenesis. Therefore, we introduce a new and simple method to simulate human AAA and construct a rat AAA model through a retroperitoneal approach.MethodsForty healthy adult Sprague Dawley (SD) rats were randomly divided into a control group, elastase + calcium chloride group (PPE+CaCl2), elastase group (PPE), and elastase + beta aminopropionitrile group (PPE+BAPN) according to a male-female ratio of 1:1, with 10 rats in each group. A retroperitoneal approach was used to free the infrarenal abdominal aorta in all four groups. In the PPE + CaCl2 group, 0.1 ml of elastase (approximately 5 U) was perfused into the arterial cavity for 20 min, and 1.0 mol/L calcium chloride was infiltrated out of the arterial cavity for 10 min. In the PPE group, 0.1 mL of elastase (approximately 5U) was perfused into the arterial cavity for 20 min, and normal saline was infiltrated out of arterial cavity for 10 min; the PPE + BAPN group combined with 0.3% BAPN drinking water/day on the basis of PPE group; the control group was treated with saline instead of elastase and calcium chloride. Abdominal aortic specimens were collected after 4 weeks of feeding. The diagnostic criteria of AAA were 50% dilation of the abdominal aorta or rupture of the aneurysm at 4 weeks after the operation. Histopathology, immunohistochemistry, quantitative PCR (qPCR), western blotting assay, gelatine zymogram, and other methods were used.ResultsThe operation time of the four groups was controlled at approximately 40 min, and the success rate of the operation was 100%. Survival rate: Control Group (100%) = PPE Group (100%) > PPE + CaCl2 Group (90%) > PPE + BAPN Group (40%); Aneurysm formation rate: PPE + BAPN Group (100%) > PPE + CaCl2 Group (80%) > PPE Group (60%) > Control Group (0%); Aneurysm rupture rate: PPE + BAPN group (60%) > PPE + CaCl2 group (12.5%) > PPE group (0%);Inflammatory cells (macrophages, T cells, B cells, dendritic cells) infiltrated in different degrees in the PPE + CaCl2, PPE and PPE + BAPN groups. Vascular thickness, elastic fiber content, collagen fiber content, and vascular smooth muscle cell content in the PPE + CaCl2 group and PPE + BNPA group were significantly lower than those in Control group (P < 0.05). The content of elastic fibers and vascular smooth muscle cells in the PPE group were significantly lower than that in Control group (P < 0.05). The expression and activity of matrix metalloproteinase 2 (MMP2) and MMP9 in the PPE + CaCl2 group, PPE group, and PPE + BNPA group were significantly higher than those in the control group (P < 0.05).ConclusionsA new, simple, and reproducible rat AAA model can be constructed by a retroperitoneal approach. The pathological features of the three models are effective simulation of human AAA inflammatory cell infiltration, protease activity enhancement, and extracellular matrix destruction. The PPE+ CaCl2 model has the advantages of a high survival rate, high aneurysm formation rate, good stability, and reproducibility. It is an ideal animal model for studying the pathogenesis of AAA. The PPE + BAPN model can simulate the characteristics of spontaneous rupture of aneurysms. It is an ideal animal model to study the mechanism of AAA rupture.

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“…On the other hand, collagen and elastic fibers are the major components of the media 9 and their structural destruction can lead to the development and progression of AD. Because beta-aminopropionitrile (BAPN) can inhibit LOX, a key enzyme in the maturation of collagen and elastic fibers 10 , it was thought to be useful in an AD mouse model 11 . Initially, the researchers added BAPN to the drinking water of the mice 12 , and then, some researchers attempted to create advanced models by combining an Ang II pump and a BAPN pump 13 .…”

Section: Introductionmentioning

confidence: 99%

Establishment of a meta-analysis based novel aortic dissection mouse model

Jiang

Liu

et al. 2022

Sci Rep

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Aortic dissection (AD) is a life-threatening disease and the detailed mechanism remains unclear. Thus, proper animal models are urgently required to better understand its pathogenesis. Our current study aims to establish a reliable, time and cost-effective mouse AD model. To conduct the meta-analysis, we searched PubMed for related studies up to 2021 and statistical analysis was conducted using Review Manager 5.4. For the animal experiment, 6-week-old male ApoE−/− mice were given β-aminopropionitrile (BAPN) at a concentration of 1 g/L for 3 weeks before being infused with saline, 1000 ng/kg/min or 2500 ng/kg/min angiotensin II (AngII) via osmotic mini pumps for 2 or 4 weeks. To determine the presence of AD, we performed B-ultrasonography, hematoxylin and eosin (H&E) staining, and van Gieson staining. The result of the meta-analysis showed that the use of BAPN and more than 2000 ng/kg/min AngII can increase the rate of AD formation, whereas administrating Ang II for more than 28 days has no significant effect on the rate of AD formation when compared with the less than 14 days group. In the present study, mice treated with BAPN combined with 2500 ng/kg/min AngII for 2 weeks (12/20) had a significantly higher AD formation rate than mice treated with BAPN combined with 1000 ng/kg/min Ang II for 4 weeks (2/10), and had a similar model formation rate compared with the mice treated withβ-aminopropionitrile combined with 2500 ng/kg/min AngII for 4 weeks (6/10). There were 3 mice (3/10) and 6 mice (6/20) who died in the group treated with β-aminopropionitrile combined with 2500 ng/kg/min AngII for 4 weeks and 2 weeks respectively, and only one mouse (1/10) died in the group treated with β-aminopropionitrile combined with 1000 ng/kg/min AngII for 4 weeks. In 6-week-old male ApoE−/− mice that received with 1 g/L BAPN in the drinking water for 3 weeks along with 2500 ng/kg/min AngII infusion via osmotic mini pumps for 2 weeks, the highest model formation rate and relative lower cumulative mortality were noted.

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Induction of thoracic aortic dissection: a mini-review of β-aminopropionitrile-related mouse models

Cited by 28 publications

References 59 publications

Compensatory aortic remodeling in Marfan syndrome protects against sexually dimorphic rupture during a BAPN challenge

Compensatory aortic remodeling in Marfan syndrome protects against sexually dimorphic rupture during a BAPN challenge

Establishment of a New Abdominal Aortic Aneurysm Model in Rats by a Retroperitoneal Approach

Establishment of a meta-analysis based novel aortic dissection mouse model

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