Aging affects K(V)7 channels and perivascular-adipose tissue-mediated vascular tone

Item Type:

Preprint

Title:

Creators Name:

Wang, Y. and Yildiz, F. and Struve, A. and Kassmann, M. and Luft, F. and Gollasch, M. and Tsvetkov, D.

Abstract:

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, QO58-lysine) in a murine model. We assessed vascular function of young and old mesenteric arteries in vitro using wire myography. 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, QO58 represents a novel tool for cardiovascular and hypertension research in aging.

Keywords:

Aging, K(V)7 Channels, Perivascular Adipose Tissue (PVAT), Transcriptome, RNA Sequencing, Animals, Mice

Source:

bioRxiv

Publisher:

Cold Spring Harbor Laboratory Press

Article Number:

2021.04.11.438975

Date:

11 April 2021

Official Publication:

https://doi.org/10.1101/2021.04.11.438975

Related to:

URL	URL Type
https://edoc.mdc-berlin.de/21168/	Final version

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