Crosstalk between Ryanodine Receptor 2 Dysfunction and FK506-Binding Proteins in Pulmonary Hypertension

Pulmonary hypertension (PH) is a complicated cardiovascular disorder marked by elevated pulmonary arterial pressure and vascular remodeling. The molecular interplay between Ryanodine Receptor 2 (RyR2) and FK506-binding protein 12.6 (FKBP12.6) emphasizes that their dissociation under hypoxic conditions results in intracellular calcium(Ca²⁺) dysregulation in pulmonary artery smooth muscle cells (PASMCs).

This review article highlights important discoveries about how mitochondrial ROS, particularly those mediated by the Rieske iron-sulfur protein (RISP), trigger RyR2 activation and the sub sequent release of Ca2+. Furthermore, it covers a process that establishes a connection between sarcoplasmic reticulum calcium signaling, which promotes vasoconstriction and vascular remodeling, and mitochondrial dysfunction.

The pathways involved inRyR2/FKBP12.6 destabilization lead to progression in PH. Moreover, targeting these pathways has been reported to be beneficial in PH management.