A Modified Method of β-Aminopropionitrile Combined with Angiotensin Ⅱ to Establish an Aortic Dissection Model in Mice

doi:10.12300/j.issn.1674-5817.2020.200

Abstract

Abstract: Objective To explore an improved method for constructing a mouse model of aortic dissection (AD). Methods AD was induced by the simultaneous administration of β-aminopropionitrile (BAPN) with angiotensin Ⅱ (Ang-Ⅱ) for 16 days in mice. One hundred 6-week-old male C57B1/6J mice were randomly divided into BAPN (BAPN 0.1 g•kg^-1•d^-1 + 0.9% saline), BAPN+Ang-Ⅱ (BAPN 0.1 g•kg^-1•d^-1 + Ang-Ⅱ), and control groups. BAPN (0.1 g•kg^-1•d^-1), freshly prepared and dissolved in drinking water, was administered to all mice in the BAPN and BAPN + Ang-Ⅱ groups for 16 days. Mice in the BAPN+Ang-Ⅱ group were treated with an additional subcutaneous injection of Ang-Ⅱ for 16 days. The concentration of Ang-Ⅱ was halved from 1.5 mg•kg-1•d-1 every week until it was set at 0.375 mg•kg^-1•d^-1 on day 15, and then maintained. The daily water intake and body weight were recorded from the beginning until the end of the study. If a mouse died during the experiment, an autopsy was performed to analyze the cause of death. On day 17, the mice were sacrificed, and each aorta was harvested. The formation of the aortic false lumen was observed pathologically using hematoxylin and eosin (HE) staining. Results Compared with the control group, the amount of water consumed and body weight in the BAPN+Ang-Ⅱ and BAPN groups were significantly reduced (P < 0.05). In the control group, the incidence of dissection and mortality was 0.0%. In the BAPN group, the incidence of AD and the mortality was 7.5% and 2.5%, respectively. In the BAPN+Ang-Ⅱ group, the incidence of AD and the mortality was 80.0% and 30.0%, respectively. Interestingly, the deaths in the BAPN+Ang-Ⅱ group occurred frequently at 1-3 days after dose adjustment, and 83.3% of the mice died a few minutes after the operation. Conclusion This modified method for constructing an AD mouse model induced by BAPN drinking combined with Ang-Ⅱ subcutaneous injection was replicable, regular, effective, cheap, and quick.

Key words: Aortic dissection, Beta-aminopropionitrile, Angiotensin Ⅱ, Mice

CLC Number:

Q95-33

CHENG Lingxia, CHEN Lin, YANG Fan, LIU Ying, CHEN Muhu, HU Yingchun, SONG Qitai, ZHONG Wu. A Modified Method of β-Aminopropionitrile Combined with Angiotensin Ⅱ to Establish an Aortic Dissection Model in Mice[J]. Laboratory Animal and Comparative Medicine, 2021, 41(4): 321-326.

Figures/Tables 4

References

[1] GOLLEDGE J, EAGLE K A.Acute aortic dissection[J]. Lancet, 2008, 372(9632): 55-66.DOI: 10.1016/S0140-6736(08)60994-0.
[2] LUO W, WANG Y, ZHANG L, et al.Critical role of cytosolic DNA and its sensing adaptor STING in aortic degeneration, dissection, and rupture[J]. Circulation, 2020, 141(1):42-66.DOI: 10.1161/CIRCULATIONAHA. 119.041460.
[3] EVANGELISTA A, ISSELBACHER E M, BOSSONE E, et al.Insights from the international registry of acute aortic dissection: a 20-year experience of collaborative clinical research[J]. Circulation, 2018, 137(17):1846-1860. DOI:10.1161/CIRCULATIONAHA.117.031264.
[4] ZHENG H Q, RONG J B, YE F M, et al.Induction of thoracic aortic dissection: a mini-review of β-aminopropionitrile-related mouse models[J]. J Zhejiang Univ Sci B, 2020, 21(8):603-610. DOI:10.1631/jzus.b2000022.
[5] BLANTON F S, MULLER W H, WARREN W D.Experimental production of dissecting aneurysms of the aorta[J]. Surgery, 1959, 45(1):81-90. DOI:10.317/jns. 1959.16.6.0705.
[6] SMITH L B, HADOKE P W, DYER E, et al.Haploinsufficiency of the murine Col3a1 locus causes aortic dissection: a novel model of the vascular type of Ehlers-Danlos syndrome[J]. Cardiovasc Res, 2011, 90(1):182-190. DOI:10.1093/cvr/cvq356.
[7] HATIPOGLU O F, MIYOSHI T, YONEZAWA T, et al.Deficiency of CD44 prevents thoracic aortic dissection in a murine model[J]. Sci Rep, 2020, 10(1):6869. DOI:10.1038/s41598-020-63824-9.
[8] BUMDELGER B, OTANI M, KARASAKI K, et al.Disruption of Osteoprotegerin has complex effects on medial destruction and adventitial fibrosis during mouse abdominal aortic aneurysm formation[J]. PLoS One, 2020, 15(7):e0235553. DOI:10.1371/journal.pone.0235553.
[9] YANG Y Y, LI L Y, JIAO X L, et al.Intermittent hypoxia alleviates beta-aminopropionitrile monofumarate induced thoracic aortic dissection in C57BL/6 mice[J]. Eur J Vasc Endovasc Surg, 2020, 59(6): 1000-1010.DIO: 10.1016/j.ejvs.2019.10.014.
[10] LEE V S, HALABI C M, HOFFMAN E P, et al.Loss of function mutation in LOX causes thoracic aortic aneurysm and dissection in humans[J]. PNAS, 2016, 113(31):8759-8764. DOI:10.1073/pnas.1601442113.
[11] TOUYZ R M, SCHIFFRIN E L.Signal transduction mechanisms mediating the physiological and pathophysiological actions of angiotensin II in vascular smooth muscle cells[J]. Pharmacol Rev, 2000, 52(4):639-672.
[12] 刘瑜婷, 高艳香, 王姗姗, 等. β-氨基丙腈饮水联合血管紧张素II埋泵建立小鼠主动脉夹层模型[J]. 中国实验动物学报, 2017, 25(4):399-403. DOI:10.3969/j.issn.1005-4847.2017.04.010.
[13] 岳东旭, 池宏伟, 鹿双双, 等. 发表文献中小鼠安死术方法的分析研究(2015—2016)[J]. 中国比较医学杂志, 2017, 27(11):91-94. DOI:10.3969.j.issn.1671-7856.2017.11.019.
[14] REN P, WU D, APPEL R, et al.Targeting the NLRP3 inflammasome with inhibitor MCC950 prevents aortic aneurysms and dissections in mice[J]. J Am Heart Assoc, 2020, 9(7): e014044. DOI:10.1161/jaha.119. 014044.
[15] 王高明, 吴海卫, 徐艳辉, 等. 胸主动脉夹层患者血浆D-二聚体和基质金属蛋白酶-8的表达水平及其临床意义[J]. 医学研究生学报, 2012, 25(2):168-171. DOI:10.3969/j.issn.1008-8199.2012.02.014.
[16] BHAVE N M, EAGLE K A.A tear in the fabric: unravelling gender differences in aortic dissection[J]. Eur Heart J, 2020, 41(26):2439-2441. DOI:10.1093/eurheartj/ehaa466.
[17] NIENABER C A, CLOUGH R E.Management of acute aortic dissection[J]. Lancet, 2015, 385(9970):800-811. DOI:10.1016/S0140-6736(14)61005-9.
[18] HAYASHI-HORI M, AOKI H, MATSUKUMA M, et al.Therapeutic effect of rapamycin on aortic dissection in mice[J]. Int J Mol Sci, 2020, 21(9).DOI: 10.3390/ijms 21093341.
[19] SHAO Y, LI G, HUANG S, et al.Effects of extracellular matrix softening on vascular smooth muscle cell dysfunction[J]. Cardiovasc Toxicol, 2020, 20(6):548-556. DOI:10.1007/s12012-020-09580-8.
[20] YANG K, REN J, LI X, et al.Prevention of aortic dissection and aneurysm via an ALDH2-mediated switch in vascular smooth muscle cell phenotype[J]. Eur Heart J, 2020(26):2442-2453.DOI: 10.1093/eurheartj/ehaa352.
[21] SARAFF K, BABAMUSTA F, CASSIS L A, et al.Aortic dissection precedes formation of aneurysms and atherosclerosis in angiotensin II-infused, apolipoprotein E-deficient mice[J]. Arterioscler Thromb Vasc Biol, 2003, 23(9):1621-1626. DOI:10.1161/01.atv.0000085631.76095.64.