Stay connected: The myoendothelial junction proteins in vascular function and dysfunction

The appropriate regulation of peripheral vascular tone is crucial for maintaining tissue perfusion. Myoendothelial junctions (MEJs), specialized connections between endothelial cells and vascular smooth muscle cells, are primarily located in peripheral resistance vessels. Therefore, these junctions, with their key membrane proteins, play a pivotal role in the physiological control of relaxation-contraction coupling in resistance arterioles, mainly mediated through endothelium-derived hyperpolarization (EDH). This review aims to illustrate the mechanisms involved in the initiation and propagation of EDH, emphasizing the role of membrane proteins involved in its generation (TRPV4, Piezo1, ASIC1a) and propagation (connexins, Notch). Finally, we discuss relevant studies on pathological events linked to EDH dysfunction and discuss novel approaches, including the effects of natural and dietary bioactive molecules, in modulating EDH-mediated vascular tone.