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KCNQ5 controls perivascular adipose tissue–mediated vasodilation

Item Type:Article
Title:KCNQ5 controls perivascular adipose tissue–mediated vasodilation
Creators Name:Tsvetkov, D. and Schleifenbaum, J. and Wang, Y. and Kassmann, M. and Polovitskaya, M.M. and Ali, M. and Schütze, S. and Rothe, M. and Luft, F.C. and Jentsch, T.J. and Gollasch, M.
Abstract:BACKGROUND: Small arteries exhibit resting tone, a partially contracted state that maintains arterial blood pressure. In arterial smooth muscle cells, potassium channels control contraction and relaxation. Perivascular adipose tissue (PVAT) has been shown to exert anticontractile effects on the blood vessels. However, the mechanisms by which PVAT signals small arteries, and their relevance remain largely unknown. We aimed to uncover key molecular components in adipose-vascular coupling. METHODS: A wide spectrum of genetic mouse models targeting Kcnq3, Kcnq4, and Kcnq5 genes (Kcnq3(–/–), Kcnq4(–/–), Kcnq5(–/–), Kcnq5(dn/dn), Kcnq4(–/–)/Kcnq5(dn/dn), and Kcnq4(–/–)/Kcnq5(–/–)), telemetry blood pressure measurements, targeted lipidomics, RNA-Seq profiling, wire-myography, patch-clamp, and sharp-electrode membrane potential measurements was used. RESULTS: We show that PVAT causes smooth muscle cell K(V)7.5 family of voltage-gated potassium (K(+)) channels to hyperpolarize the membrane potential. This effect relaxes small arteries and regulates blood pressure. Oxygenation of polyunsaturated fats generates oxylipins, a superclass of lipid mediators. We identified numerous oxylipins released by PVAT, which potentiate vasodilatory action in small arteries by opening smooth muscle cell K(V)7.5 family of voltage-gated potassium (K(+)) channels. CONCLUSIONS: Our results reveal a key molecular function of the K(V)7.5 family of voltage-gated potassium (K(+)) channels in the adipose-vascular coupling, translating PVAT signals, particularly oxylipins, to the central physiological function of vasoregulation. This novel pathway opens new therapeutic perspectives.
Keywords:Hypertension, Oxylipins, Animals, Mice
Publisher:American Heart Association
Page Range:561-571
Date:March 2024
Official Publication:https://doi.org/10.1161/hypertensionaha.123.21834
PubMed:View item in PubMed

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