TRPV4 in Cerebral Small Vessel Disease: A key interacting partner

Cerebral small vessel disease (cSVD) is a major cause of vascular cognitive impairment and dementia. The underlying disease mechanisms are centered around the dysfunction of the neurovascular unit and include an impairment of the blood-brain barrier (BBB) permeability, a decreased cerebrovascular reactivity and cerebral hypoperfusion. The cells composing the neurovascular unit express a wide variety of mechanosensitive ion channels that are relevant for these processes. Recent research has increasingly focused on the mechanobiology of cerebral microvessels with recent evidence pointing towards a significant role of transient receptor potential vanilloid 4 (TRPV4). This Ca²⁺-permeable channel regulates key physiological functions, including vascular tone, angiogenesis, BBB integrity and neuroinflammation. Beyond its physiological role, recent evidence implicates TRPV4 in pathological processes such as cerebrovascular remodelling, impaired cerebrovascular reactivity, and BBB dysfunction. In this review, we explore the multiple roles of TRPV4 within the neurovascular unit, its interactions with key molecular partners, and we discuss evidence for its potential contribution to cSVD.