Proposed sequence of events arising from Kcnk3-LOF mutation in context of LV pressure overload. In context of LV pressure overload, we propose that Kcnk3-LOF mutation promotes (i) the disruption of pulmonary endothelium integrity (with a decreased expression of p120 catenin in lung from Sham-Kcnk3-mutated vs Sham-WT rats) which leads to lung perivascular oedema and PA adventitial remodelling, (ii) the inflammatory signalling (Increased expression of IL-6 in lung, LV, RV and LA from AAC-Kcnk3-mutated rats) which leads to increase PASMC proliferation and promoting pulmonary vascular remodelling and parenchymal remodelling. (i) and (ii) contribute to the increase of pulmonary vascular resistances, and (iii) the cardiac fibrosis (with an increased expression of Col1A1 and periostin in LV and RV from AAC-Kcnk3-mutated rats) link to LV diastolic dysfunction, decreased of LA compliance and abnormal pulmonary venous remodelling. All together these deregulations act in favour of the aggravation of pulmonary hypertension and the consequent RV hypertrophy and dysfunction. All these events are responsible for the development of more severe PH-induced by LV pressure overload in Kcnk3-mutated rats.