Ventricular remodeling and function: insights using murine echocardiography

Abstract

Extracellular matrix disturbances play an important role in the development of ventricular remodeling and failure. Genetically modified mice with abnormalities in the synthesis and degradation of extracellular matrix have been generated, in particular mice with deletion or overexpression of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs). Echocardiography is ideally suited to serially evaluate left ventricular (LV) size and function, thus defining the progression of LV remodeling and failure. This Review describes the echocardiographic parameters that may provide insights into the development of ventricular remodeling and heart failure. The application of echocardiography to study LV remodeling and function after myocardial infarction and LV pressure-overload in wild-type mice and mice deficient or overexpressing MMPs or TIMPs is then detailed. Finally, using the example of mice deficient in nitric oxide synthase 3, a cautionary example is given illustrating discrepancies between the cardiac echocardiographic phenotype and modifications of the extracellular matrix.

Figure 1

M-mode tracing obtained on a wild-type mouse. LV_EDD: left ventricular end diastolic diameter; LV_ESD: left ventricular end systolic diameter; AWT: anterior wall thickness; PWT: posterior wall thickness.

Figure 2

Parasternal long axis (left) and short axis (right) views obtained on a control wild-type mouse (Panel A), a mouse 2 days after myocardial infarction (Panel B) and a mouse 28 days after transverse aortic banding (Panel C). Schematic of views in control mouse (Panel D). LV: left ventricle; LA: left atrium; RV: right ventricle; Ao: aorta.

Figure 3

Collagen deposition (red staining) in the LV of wild-type (Panel A) and NOS3-deficient (Panel B) mice 28 days after aortic banding. Twenty-eight days after aortic banding, collagen deposition was increased in NOS3-deficient as compared to wild-type mice. Reprinted with permission of the American Journal of Physiology.