Dataset for: Regional Septal Hinge-Point Injury Contributes to Adverse Biventricular Interactions in Pulmonary Hypertension
datasetposted on 24.07.2017, 10:38 by Eva Amalie Nielsen, KENICHI OKUMURA, Mei Sun, Vibeke E Hjortdal, Andrew N Redington, Mark K Friedberg
Background: Death and morbidity in pulmonary arterial hypertension (PAH) are often due to right ventricular (RV) failure and associated left ventricular (LV) dysfunction. We investigated regional myocardial remodeling and function as the basis for adverse ventricular-ventricular interactions in experimental chronic RV pressure overload. Methods and Results: Two distinct animal models were studied: A) A rabbit model of increased RV pressure-load through progressive pulmonary artery banding B) A rat model of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). Regional myocardial function was assessed by speckle-tracking strain echocardiography and ventricular pressures measured by catheterization before termination. Regional RV and LV myocardium was analyzed for collagen content, apoptosis and pro-fibrotic signaling gene and protein expression. Although the RV developed more fibrosis than the LV; in both models the LV was substantially affected. In both ventricles, particularly the LV, fibrosis developed predominantly at the septal hinge-point regions in association with decreased regional and global circumferential strain, reduced global RV and LV function and up-regulation of regional transforming growth factor-β1 (TGFβ1) and apoptosis signaling. A group of PAH rats who received the TGFβ blocker SB431542 showed improved RV function and reduced regional hinge-point myocardial fibrosis. Conclusion: RV pressure-loading and PAH lead to biventricular TGFβ1 signaling, fibrosis and apoptosis, predominantly at the septal hinge-point regions, in association with regional myocardial dysfunction. This suggests that altered geometry and wall stress lead to adverse RV-LV interactions through the septal hinge-points to induce LV fibrosis and dysfunction.