Arterial Hypertension · Published 2025-02-11 · DOI 10.5603/ah.108127
Resistant hypertension remains a significant global health concern and is a major contributor to cardiovascular complications such as vascular dysfunction and cardiac fibrosis. Emerging evidence suggests that transient receptor potential canonical (TRPC) channels, particularly TRPC3 and TRPC6, play pivotal roles in this condition by mediating calcium influx through both store-operated and receptor-operated calcium entry pathways. Disruption of calcium homeostasis is a central feature in cardiovascular pathology, promoting sustained vasoconstriction, increased vascular stiffness, and pathological cardiac remodelling. TRPC3 and TRPC6 are non-selective cation channels activated by mechanical and neurohumoral stimuli, and their dysregulation contributes directly to these pathological processes. In particular, these channels are upregulated in cardiac fibrosis, facilitating calcium-dependent activation of cardiac fibroblasts into myofibroblasts. This transition leads to excessive extracellular matrix production, notably collagen deposition, which increases myocardial stiffness and impairs cardiac function. Thus, aberrant calcium signalling through TRPC channels not only underlies vascular dysfunction in resistant hypertension but also drives the development and progression of cardiac fibrosis. This review explores the expression and functional roles of TRPC channels within the cardiovascular system, their contributions to the pathophysiology of resistant hypertension and cardiac fibrosis, and the therapeutic potential of TRPC channel inhibitors as novel strategies to combat both elevated blood pressure and fibrotic remodelling.
Abstract from DOAJ. Public domain (CC0 1.0).
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