Potential roles for transient receptor potential vanilloid 1 in heart failure with preserved ejection fraction

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome in which diastolic dysfunction develops against a background of interacting mechanisms: inflammation, oxidative stress, impaired calcium homeostasis, myocardial fibrosis, coronary microvascular dysfunction, mitochondrial impairment, and neurohumoral activation. Effective mechanism-targeted therapies remain limited. Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel expressed in cardiac sensory nerves, vascular endothelial cells, immune cells, and possibly other cardiovascular cell populations. It responds to diverse physical and chemical stimuli and may influence calcium handling, inflammatory signaling, oxidative stress, myocardial fibrosis, mitophagy, and ferroptosis. Preclinical studies have linked altered TRPV1 expression or activity to myocardial remodeling, impaired relaxation, microvascular dysfunction, and heart failure progression, but direct evidence in HFpEF is still sparse. This review summarizes the biological properties of TRPV1, considers how its signaling might intersect with HFpEF pathophysiology, reviews experimental TRPV1-targeted interventions, and identifies the evidence needed before TRPV1 can be evaluated as a potential therapeutic target.