Pressure Overload-Induced Ventricular Crosstalk Activates Regenerative Mechanisms in the Contralateral Ventricle in Neonatal Mice [scRNA-Seq]

Given the transient regenerative capacity of the neonatal heart, we investigated whether pressure overload in one ventricle activates adaptive and regenerative responses in the contralateral ventricle. We induced pressure overload in neonatal mice at postnatal day (P) 0-1 using pulmonary artery banding (nPAB) or transverse aortic constriction (nTAC).

In both models, ventricular mass and wall thickness increased not only in the targeted ventricle but also in the contralateral ventricle. These changes were accompanied by cardiomyocyte hyperplasia, preserved systolic function, and enhanced angiogenesis without fibrosis. Bulk and single-nucleus RNA sequencing revealed coordinated activation of pro-proliferative and angiogenic gene programs in both ventricles, including expansion of a cycling cardiomyocyte subpopulation characterized by Ccnd2.