Intracellular remodelling of Ca2+ stores in pulmonary hypertension

This editorial refers to ‘Stretch-induced Ca2+ signalling in vascular smooth muscle cells depends on Ca2+ store segregation’ by G. Gilbert et al. , pp. 313–323, this issue. The low resistance of the pulmonary circulation, a function of its unique structure and regulation, normally allows it to accept the entire cardiac output in the pulmonary vascular bed while maintaining an internal pressure that is low enough to prevent pulmonary oedema. In pulmonary hypertension (PH), however, pulmonary vascular resistance can increase enormously due to structural remodelling and abnormalities in the regulation of pulmonary artery (PA) diameter. Both changes are driven, at least in part, by increases in the intracellular Ca2+ concentration ([Ca2+]i) in PA smooth muscle cells (PASMCs). This is associated with the up-regulation of multiple pathways mediating the influx of Ca2+ into these cells.1 [Ca2+]i, however, is not determined by Ca2+ influx alone; there is recent evidence2 that the expression of SERCA2a, which mediates Ca2+ uptake into the sarcoplasmic reticulum (SR), is decreased in PASMCs from humans with PH.An elegant study by Gilbert et al. 3 in the current issue of Cardiovascular Research now demonstrates that the abnormalities in intracellular Ca2+ handling in PH go well beyond SERCA; they find that two animal models of PH exhibit a re-organization of intracellular Ca2+ stores of …