Left ventricular pressure-loading improves pressure-induced right ventricular remodeling by redistributing mechanical load and reducing mechanosignaling.

Right ventricular (RV) function under pressure overload (PO) is critical in congenital heart disease outcomes. While moderate left ventricular (LV) pressure-loading has been shown to benefit RV function, the mechanisms and optimal degree of loading remain unclear. This study investigated whether increasing LV afterload could enhance RV function, remodeling, and molecular signaling. Using computational modeling and an in vivo "double-banding" (DB) approach in Sprague-Dawley rats-constricting both the pulmonary artery (PA) and transverse aorta-the effects of LV loading were assessed. Modeling suggested that LV pressure-loading improves RV contractility by homogenizing RV load. In vivo, DB rats exhibited higher tricuspid annular plane systolic excursion (TAPSE) compared to those with only pulmonary artery banding (PAB). Hemodynamic analysis showed reduced end-diastolic pressure (EDP) and increased end-diastolic pressure-volume relationship (EDPVR) in DB rats. Histological examination revealed less RV fibrosis in DB rats with moderate LV loading (DBmod) than in those with mild loading (DBmild) or PAB. Molecular studies indicated that markers of fibrosis and maladaptive signaling were elevated in PAB RVs but normalized or downregulated in DBmod RVs. These findings suggest that moderate LV pressure-loading during RV-PO improves RV remodeling and function, providing mechanistic insights and potential therapeutic strategies for congenital heart disease.