Aging Affects KV7 Channels and Perivascular Adipose Tissue-Mediated Vascular Tone

Aging is an independent risk factor for hypertension, cardiovascular morbidity, and mortality. However, detailed mechanisms linking aging to cardiovascular disease are unclear. We studied the aging effects on the role of perivascular adipose tissue and downstream vasoconstriction targets, voltage-de...

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Autores principales:	Yibin Wang, Fatima Yildiz, Andrey Struve, Mario Kassmann, Lajos Markó, May-Britt Köhler, Friedrich C. Luft, Maik Gollasch, Dmitry Tsvetkov
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	aging KV7 channels perivascular adipose tissue transcriptome RNA sequencing Physiology QP1-981
Acceso en línea:	https://doaj.org/article/31dd00349dd6488386695c75d383d9bd
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spelling	oai:doaj.org-article:31dd00349dd6488386695c75d383d9bd2021-12-01T07:26:28ZAging Affects KV7 Channels and Perivascular Adipose Tissue-Mediated Vascular Tone1664-042X10.3389/fphys.2021.749709https://doaj.org/article/31dd00349dd6488386695c75d383d9bd2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphys.2021.749709/fullhttps://doaj.org/toc/1664-042XAging is an independent risk factor for hypertension, cardiovascular morbidity, and mortality. However, detailed mechanisms linking aging to cardiovascular disease are unclear. We studied the aging effects on the role of perivascular adipose tissue and downstream vasoconstriction targets, voltage-dependent KV7 channels, and their pharmacological modulators (flupirtine, retigabine, QO58, and QO58-lysine) in a murine model. We assessed vascular function of young and old mesenteric arteries in vitro using wire myography and membrane potential measurements with sharp electrodes. We also performed bulk RNA sequencing and quantitative reverse transcription-polymerase chain reaction tests in mesenteric arteries and perivascular adipose tissue to elucidate molecular underpinnings of age-related phenotypes. Results revealed impaired perivascular adipose tissue-mediated control of vascular tone particularly via KV7.3–5 channels with increased age through metabolic and inflammatory processes and release of perivascular adipose tissue-derived relaxation factors. Moreover, QO58 was identified as novel pharmacological vasodilator to activate XE991-sensitive KCNQ channels in old mesenteric arteries. Our data suggest that targeting inflammation and metabolism in perivascular adipose tissue could represent novel approaches to restore vascular function during aging. Furthermore, KV7.3–5 channels represent a promising target in cardiovascular aging.Yibin WangFatima YildizAndrey StruveMario KassmannMario KassmannLajos MarkóMay-Britt KöhlerFriedrich C. LuftMaik GollaschMaik GollaschDmitry TsvetkovDmitry TsvetkovFrontiers Media S.A.articleagingKV7 channelsperivascular adipose tissuetranscriptomeRNA sequencingPhysiologyQP1-981ENFrontiers in Physiology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	aging KV7 channels perivascular adipose tissue transcriptome RNA sequencing Physiology QP1-981
spellingShingle	aging KV7 channels perivascular adipose tissue transcriptome RNA sequencing Physiology QP1-981 Yibin Wang Fatima Yildiz Andrey Struve Mario Kassmann Mario Kassmann Lajos Markó May-Britt Köhler Friedrich C. Luft Maik Gollasch Maik Gollasch Dmitry Tsvetkov Dmitry Tsvetkov Aging Affects KV7 Channels and Perivascular Adipose Tissue-Mediated Vascular Tone
description	Aging is an independent risk factor for hypertension, cardiovascular morbidity, and mortality. However, detailed mechanisms linking aging to cardiovascular disease are unclear. We studied the aging effects on the role of perivascular adipose tissue and downstream vasoconstriction targets, voltage-dependent KV7 channels, and their pharmacological modulators (flupirtine, retigabine, QO58, and QO58-lysine) in a murine model. We assessed vascular function of young and old mesenteric arteries in vitro using wire myography and membrane potential measurements with sharp electrodes. We also performed bulk RNA sequencing and quantitative reverse transcription-polymerase chain reaction tests in mesenteric arteries and perivascular adipose tissue to elucidate molecular underpinnings of age-related phenotypes. Results revealed impaired perivascular adipose tissue-mediated control of vascular tone particularly via KV7.3–5 channels with increased age through metabolic and inflammatory processes and release of perivascular adipose tissue-derived relaxation factors. Moreover, QO58 was identified as novel pharmacological vasodilator to activate XE991-sensitive KCNQ channels in old mesenteric arteries. Our data suggest that targeting inflammation and metabolism in perivascular adipose tissue could represent novel approaches to restore vascular function during aging. Furthermore, KV7.3–5 channels represent a promising target in cardiovascular aging.
format	article
author	Yibin Wang Fatima Yildiz Andrey Struve Mario Kassmann Mario Kassmann Lajos Markó May-Britt Köhler Friedrich C. Luft Maik Gollasch Maik Gollasch Dmitry Tsvetkov Dmitry Tsvetkov
author_facet	Yibin Wang Fatima Yildiz Andrey Struve Mario Kassmann Mario Kassmann Lajos Markó May-Britt Köhler Friedrich C. Luft Maik Gollasch Maik Gollasch Dmitry Tsvetkov Dmitry Tsvetkov
author_sort	Yibin Wang
title	Aging Affects KV7 Channels and Perivascular Adipose Tissue-Mediated Vascular Tone
title_short	Aging Affects KV7 Channels and Perivascular Adipose Tissue-Mediated Vascular Tone
title_full	Aging Affects KV7 Channels and Perivascular Adipose Tissue-Mediated Vascular Tone
title_fullStr	Aging Affects KV7 Channels and Perivascular Adipose Tissue-Mediated Vascular Tone
title_full_unstemmed	Aging Affects KV7 Channels and Perivascular Adipose Tissue-Mediated Vascular Tone
title_sort	aging affects kv7 channels and perivascular adipose tissue-mediated vascular tone
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/31dd00349dd6488386695c75d383d9bd
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Aging Affects KV7 Channels and Perivascular Adipose Tissue-Mediated Vascular Tone

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