title: Angiotensin II-induced dilated cardiomyopathy in Balb/c but not C57BL/6J mice.
abstract: Balb/c mice, which are T-helper lymphocyte 2 (Th2) responders, are highly susceptible to infectious and non-infectious heart diseases, whereas C57BL/6 mice (Th1 responders) are not. Angiotensin II (Ang II) is not only a vasopressor but also a pro-inflammatory factor that leads to cardiac hypertrophy, fibrosis and dysfunction. We hypothesized that Ang II exacerbates cardiac damage in Balb/c but not in C57BL/6 mice even though both strains have a similar level of hypertension. Twelve-week-old male C57BL/6J and Balb/c mice received either vehicle or Ang II (1.4 mg kg(-1) day(-1), s.c. via osmotic minipump) for 8 weeks. At baseline, Balb/c mice exhibited the following: (1) a lower heart rate; (2) an enlarged left ventricular chamber; (3) a lower ejection fraction and shortening fraction; and (4) twice the left ventricular collagen deposition of age-matched C57BL/6J mice. Angiotensin II raised systolic blood pressure (to ∼150 mmHg) and induced cardiomyocyte hypertrophy in a similar manner in both strains. While C57BL/6J mice developed compensatory concentric hypertrophy and fibrosis in response to Ang II, Balb/c mice demonstrated severe left ventricular chamber dilatation, wall thinning and fibrosis, leading to congestive heart failure as evidenced by dramatically decreased ejection fraction and lung congestion (significant increase in lung weight), which are both characteristic of dilated cardiomyopathy. Our study suggests that the Th phenotype plays an active role in cardiac remodelling and function both in basal conditions and in hypertension. Angiotensin II-induced dilated cardiomyopathy in Balb/c mice is an ideal animal model for studying the impact of the adaptive immune system on cardiac remodelling and function and for testing strategies to prevent or treat hypertension-associated heart failure.
authors: Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, Detroit, MI 48202, USA. nrhaleb1@hfhs.org
authors: Hongmei
authors: H
authors: Peng
authors: Xiao-Ping
authors: XP
authors: Yang
authors: Oscar A
authors: OA
authors: Carretero
authors: Pablo
authors: P
authors: Nakagawa
authors: Martin
authors: M
authors: D'Ambrosio
authors: Pablo
authors: P
authors: Leung
authors: Jiang
authors: J
authors: Xu
authors: Edward L
authors: EL
authors: Peterson
authors: Germán E
authors: GE
authors: González
authors: Pamela
authors: P
authors: Harding
authors: Nour-Eddine
authors: NE
authors: Rhaleb
references: Science. 2001 Jan 12;291(5502):319-22
references: 11209085
references: J Clin Immunol. 2006 Jan;26(1):33-9
references: 16418801
references: Am J Physiol Heart Circ Physiol. 2011 Mar;300(3):H1053-61
references: 21193590
references: Am J Physiol. 1999 Nov;277(5):H1967-74
references: 10564153
references: Ann N Y Acad Sci. 2002 Dec;975:57-67
references: 12538154
references: Cardiol Rev. 2009 Sep-Oct;17(5):216-21
references: 19690472
references: Am J Pathol. 2001 Jul;159(1):193-203
references: 11438466
references: Cell. 1992 Mar 6;68(5):855-67
references: 1547487
references: Am J Physiol Heart Circ Physiol. 2005 Aug;289(2):H643-51
references: 16014617
references: Physiol Rev. 2006 Jul;86(3):747-803
references: 16816138
references: Int J Biochem Cell Biol. 2003 Jun;35(6):881-900
references: 12676174
references: J Clin Invest. 1993 Dec;92(6):2877-82
references: 7504694
references: Hypertension. 2006 Jul;48(1):98-104
references: 16735642
references: Hypertension. 2002 Sep;40(3):244-50
references: 12215461
references: Cell. 1994 Jan 28;76(2):241-51
references: 7904900
references: J Immunol. 2003 Oct 1;171(7):3655-67
references: 14500663
references: J Immunol. 1986 Apr 1;136(7):2348-57
references: 2419430
references: Am J Pathol. 1986 Feb;122(2):284-91
references: 3004227
references: Circ Res. 1998 Jun 1;82(10):1035-42
references: 9622156
references: J Immunol. 2017 Oct 1;199(7):2194-2201
references: 28923981
references: J Immunol. 2000 May 1;164(9):4819-25
references: 10779790
references: J Clin Immunol. 2005 Jul;25(4):376-84
references: 16133994
references: Hypertension. 1995 May;25(5):1111-5
references: 7737724
references: FASEB J. 2001 Nov;15(13):2545-7
references: 11641263
references: J Clin Invest. 2004 Jul;114(2):300-8
references: 15254597
references: J Mol Cell Cardiol. 2010 Sep;49(3):499-507
references: 20488188
references: Arch Pathol. 1964 Jul;78:69-72
references: 14150734
references: J Cardiovasc Pharmacol. 2008 Jan;51(1):62-70
references: 18209570
references: Hypertension. 2010 Apr;55(4):953-60
references: 20157054