A New Mouse Model for Introduction of Aortic Aneurysm by Implantation of Deoxycorticosterone Acetate Pellets or Aldosterone Infusion in the Presence of High Salt

  • Shu Liu
  • Ming C. Gong
  • Zhenheng GuoEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1614)


Dysfunction of the renin-angiotensin-aldosterone system (RAAS) has been implicated in the etiologies of many cardiovascular diseases, including aortic aneurysm. In particular, the infusion of angiotensin II (Ang II) in the apolipoprotein E-deficient mice (apoE−/−) and low density lipoprotein receptor knockout mice (LDLR−/−) to induce aortic aneurysm has been extensively used in the field. In contrast, whether aldosterone (Aldo), an essential component of RAAS and a downstream effector of Ang II, is involved in aortic aneurysm is largely unknown. Here, we describe a new animal model for induction of aortic aneurysm in mice in which administration of deoxycorticosterone acetate (DOCA) and high salt or aldosterone and high salt, but not DOCA or high salt alone, to C57BL/6 male mice can potently induce aortic aneurysm formation and rupture in an age-dependent manner. This new aortic aneurysm mouse model is different from Ang II infusion mouse model and exhibits several unique features that mimic human aortic aneurysm.

Key words

Aneurysm Angiotensin Aldosterone Sodium Deoxycorticosterone 



This work was supported by NIH grants HL106843 and HL125228 (to M.C. Gong and Z. Guo) and VA Merit Award BX002141 (to Z. Guo) as well as a National Institute of General.

Medical Sciences grant (P20 GM103527-05 to L. Cassis).


  1. 1.
    Hiratzka LF, Bakris GL, Beckman JA et al (2010) 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with thoracic aortic disease. A report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine. J Am Coll Cardiol 55:e27–e129CrossRefPubMedGoogle Scholar
  2. 2.
    Isselbacher EM (2005) Thoracic and abdominal aortic aneurysms. Circulation 111:816–828CrossRefPubMedGoogle Scholar
  3. 3.
    Lindsay ME, Dietz HC (2011) Lessons on the pathogenesis of aneurysm from heritable conditions. Nature 473:308–316CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Golledge J, Muller J, Daugherty A et al (2006) Abdominal aortic aneurysm: pathogenesis and implications for management. Arterioscler Thromb Vasc Biol 26:2605–2613CrossRefPubMedGoogle Scholar
  5. 5.
    Cassis LA, Gupte M, Thayer S et al (2009) ANG II infusion promotes abdominal aortic aneurysms independent of increased blood pressure in hypercholesterolemic mice. Am J Physiol Heart Circ Physiol 296:H1660–H1665CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Cassis LA, Helton MJ, Howatt DA et al (2005) Aldosterone does not mediate angiotensin II-induced atherosclerosis and abdominal aortic aneurysms. Br J Pharmacol 144:443–448CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Daugherty A, Manning MW, Cassis LA (2000) Angiotensin II promotes atherosclerotic lesions and aneurysms in apolipoprotein E-deficient mice. J Clin Invest 105:1605–1612CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Rateri DL, Moorleghen JJ, Balakrishnan A et al (2011) Endothelial cell-specific deficiency of Ang II type 1a receptors attenuates Ang II-induced ascending aortic aneurysms in LDL receptor−/− mice. Circ Res 108:574–581CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Thomas M, Gavrila D, Mccormick ML et al (2006) Deletion of p47phox attenuates angiotensin II-induced abdominal aortic aneurysm formation in apolipoprotein E-deficient mice. Circulation 114:404–413CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Zhang X, Thatcher SE, Rateri DL et al (2012) Transient exposure of neonatal female mice to testosterone abrogates the sexual dimorphism of abdominal aortic aneurysms. Circ Res 110:e73–e85CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Liu S, Xie Z, Daugherty A et al (2013) Mineralocorticoid receptor agonists induce mouse aortic aneurysm formation and rupture in the presence of high salt. Arterioscler Thromb Vasc Biol 33:1568–1579CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Weber KT (2001) Aldosterone in congestive heart failure. N Engl J Med 345:1689–1697CrossRefPubMedGoogle Scholar
  13. 13.
    He BJ, Joiner ML, Singh MV et al (2011) Oxidation of CaMKII determines the cardiotoxic effects of aldosterone. Nat Med 17:1610–1618CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Barisione C, Charnigo R, Howatt DA et al (2006) Rapid dilation of the abdominal aorta during infusion of angiotensin II detected by noninvasive high-frequency ultrasonography. J Vasc Surg 44:372–376CrossRefPubMedGoogle Scholar
  15. 15.
    Mekada K, Abe K, Murakami A et al (2009) Genetic differences among C57BL/6 substrains. Exp Anim 58:141–149CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media LLC 2017

Authors and Affiliations

  1. 1.Department of PhysiologyUniversity of KentuckyLexingtonUSA
  2. 2.Research and Development, Lexington Veterans Affairs Medical CenterUniversity of KentuckyLexingtonUSA
  3. 3.Saha Cardiovascular Research CenterUniversity of KentuckyLexingtonUSA
  4. 4.Department of Pharmacology and Nutritional ScienceUniversity of KentuckyLexingtonUSA

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