Angiotensin II-induced dilated cardiomyopathy in Balb/c but not C57BL/6J mice. Exp Physiol 2011 Aug;96(8):756-64
Date
05/24/2011Pubmed ID
21602297Pubmed Central ID
PMC3256574DOI
10.1113/expphysiol.2011.057612Scopus ID
2-s2.0-79960699648 (requires institutional sign-in at Scopus site) 53 CitationsAbstract
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.
Author List
Peng H, Yang XP, Carretero OA, Nakagawa P, D'Ambrosio M, Leung P, Xu J, Peterson EL, González GE, Harding P, Rhaleb NEAuthor
Pablo Nakagawa PhD Assistant Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Angiotensin IIAnimals
Blood Pressure
Cardiomyopathy, Dilated
Collagen
Fibrosis
Heart Failure
Heart Rate
Interferon-gamma
Interleukin-4
Liver
Lung
Male
Mice
Mice, Inbred C57BL
Myocytes, Cardiac
Phenotype
Pulmonary Atelectasis
Stroke Volume
T-Lymphocytes, Helper-Inducer
Ventricular Remodeling