Right ventricular remodeling in response to pressure overload

Right ventricular hypertrophy (RVH) is an adaptive response to increased hemodynamic load in several types of pulmonary and congenital heart diseases. However, chronic overload may result in right ventricular failure, which further complicates the disease progression. The aim of the study was to investigate the time course of structural and functional changes of the heart in the murine model of pressure overload-induced RVH and clarify the driving molecular mechanisms of the remodeling process.

RVH was induced in male C57 B l/6 mice by the pulmonary artery (PAB) by reduction of the vessel diameter to approximately 70%. Sham-operated animals served as controls. Using ultrasound biomicroscopy we assessed the changes of RV structure and function at different time points for a period of 21 days. In our model, the magnitude of the pressure overload was sufficient to produce significant RVH within a few days after banding with further progression up to the 21st day after PAB. Heart remodeling in the PAB mice was characterized by dilatation and increased free wall thickness of the right ventricle, flattening of the interventricular septum and compression of the left ventricle. These structural changes were associated with impaired right ventricular function. Histological examination revealed increased right ventricular collagen deposition in the PAB mice. Expressions of right ventricular hypertrophic marker genes are significantly increased in the PAB mice.

Thus, PAB represents a good model to investigate a remodeling process in the heart during the development of RVH. This information may provide important insights into the pathophysiology of adaptive or non-adaptive cardiac hypertrophy in response to a pressure overload.