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

Giulia Querio; Federica Geddo; Susanna Antoniotti; Saveria Femminò; Maria Pia Gallo; Claudia Penna; Pasquale Pagliaro

doi:10.1016/j.vph.2025.107463

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

Vascul Pharmacol. 2025 Jan 14:158:107463. doi: 10.1016/j.vph.2025.107463. Online ahead of print.

Authors

Giulia Querio¹, Federica Geddo², Susanna Antoniotti³, Saveria Femminò⁴, Maria Pia Gallo⁵, Claudia Penna⁶, Pasquale Pagliaro⁷

Affiliations

¹ Department of Clinical and Biological Sciences, University of Torino, Regione Gonzole 10, 10043 Orbassano, Italy. Electronic address: [email protected].
² Department of Life Sciences and Systems Biology, University of Torino, Via Accademia Albertina 13, 10123 Torino, Italy. Electronic address: [email protected].
³ Department of Life Sciences and Systems Biology, University of Torino, Via Accademia Albertina 13, 10123 Torino, Italy. Electronic address: [email protected].
⁴ Department of Clinical and Biological Sciences, University of Torino, Regione Gonzole 10, 10043 Orbassano, Italy. Electronic address: [email protected].
⁵ Department of Life Sciences and Systems Biology, University of Torino, Via Accademia Albertina 13, 10123 Torino, Italy. Electronic address: [email protected].
⁶ Department of Clinical and Biological Sciences, University of Torino, Regione Gonzole 10, 10043 Orbassano, Italy; National Institute for Cardiovascular Research (INRC), 40126 Bologna, Italy. Electronic address: [email protected].
⁷ Department of Clinical and Biological Sciences, University of Torino, Regione Gonzole 10, 10043 Orbassano, Italy. Electronic address: [email protected].

PMID: 39814089
DOI: 10.1016/j.vph.2025.107463

Abstract

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.

Keywords: Endothelium-derived hyperpolarization; Membrane proteins endothelial cells; Myoendothelial junctions; Resistance arterioles; Vascular smooth muscle cells; Vascular tone.