Pampols-Perez Mireia, Fürst Carina, Sánchez-Carranza Oscar, Cano Elena, Garcia-Contreras Jonathan Alexis, Mais Lisa, Luo Wenhan, Raimundo Sandra, Lindberg Eric L, Taube Martin, Heuser Arnd, Sporbert Anje, Kainmueller Dagmar, Bernabeu Miguel O, Hübner Norbert, Gerhardt Holger, Lewin Gary R, Hammes Annette
Molecular Pathways in Cortical Development, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
Institute for Biology, Free University of Berlin, Berlin, Germany.
Nat Cardiovasc Res. 2025 Jun 27. doi: 10.1038/s44161-025-00677-3.
Coronary arteries develop under constant mechanical stress. However, the role of mechanosensitive ion channels in this process remains poorly understood. Here we show that the ion channel PIEZO2, which responds to mechanical stimuli, is expressed in specific coronary endothelial cell populations during a critical phase of coronary vasculature remodeling. These Piezo2 coronary endothelial cells show distinct transcriptional profiles and have mechanically activated ionic currents. Strikingly, PIEZO2 loss-of-function mouse embryos and mice with human pathogenic variants of PIEZO2 show abnormal coronary vessel development and cardiac left ventricular hyperplasia. We conclude that an optimal balance of PIEZO2 channel function contributes to proper coronary vessel formation, structural integrity and remodeling, and is likely to support normal cardiac function. Our study highlights the importance of mechanical cues in cardiovascular development and suggests that defects in this mechanosensing pathway may contribute to congenital heart conditions.
冠状动脉在持续的机械应力作用下发育。然而，机械敏感离子通道在此过程中的作用仍知之甚少。在此，我们表明，对机械刺激有反应的离子通道PIEZO2在冠状动脉血管重塑的关键阶段，在特定的冠状动脉内皮细胞群体中表达。这些表达PIEZO2的冠状动脉内皮细胞表现出独特的转录谱，并且具有机械激活的离子电流。令人惊讶的是，PIEZO2功能丧失的小鼠胚胎以及携带PIEZO2人类致病变体的小鼠表现出冠状动脉发育异常和心脏左心室增生。我们得出结论，PIEZO2通道功能的最佳平衡有助于冠状动脉的正常形成、结构完整性和重塑，并且可能支持正常的心脏功能。我们的研究突出了机械信号在心血管发育中的重要性，并表明这种机械传感途径的缺陷可能导致先天性心脏病。
