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

Publication ,  Journal Article
Wang, Y; Yildiz, F; Struve, A; Kassmann, M; Markó, L; Köhler, MB; Luft, FC; Gollasch, M; Tsvetkov, D
Published in: Frontiers in Physiology
November 26, 2021

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.

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Published In

Frontiers in Physiology

DOI

EISSN

1664-042X

Publication Date

November 26, 2021

Volume

12

Related Subject Headings

  • 3208 Medical physiology
  • 3101 Biochemistry and cell biology
  • 1701 Psychology
  • 1116 Medical Physiology
  • 0606 Physiology
 

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Wang, Y., Yildiz, F., Struve, A., Kassmann, M., Markó, L., Köhler, M. B., … Tsvetkov, D. (2021). Aging Affects KV7 Channels and Perivascular Adipose Tissue-Mediated Vascular Tone. Frontiers in Physiology, 12. https://doi.org/10.3389/fphys.2021.749709
Wang, Y., F. Yildiz, A. Struve, M. Kassmann, L. Markó, M. B. Köhler, F. C. Luft, M. Gollasch, and D. Tsvetkov. “Aging Affects KV7 Channels and Perivascular Adipose Tissue-Mediated Vascular Tone.” Frontiers in Physiology 12 (November 26, 2021). https://doi.org/10.3389/fphys.2021.749709.
Wang Y, Yildiz F, Struve A, Kassmann M, Markó L, Köhler MB, et al. Aging Affects KV7 Channels and Perivascular Adipose Tissue-Mediated Vascular Tone. Frontiers in Physiology. 2021 Nov 26;12.
Wang, Y., et al. “Aging Affects KV7 Channels and Perivascular Adipose Tissue-Mediated Vascular Tone.” Frontiers in Physiology, vol. 12, Nov. 2021. Scopus, doi:10.3389/fphys.2021.749709.
Wang Y, Yildiz F, Struve A, Kassmann M, Markó L, Köhler MB, Luft FC, Gollasch M, Tsvetkov D. Aging Affects KV7 Channels and Perivascular Adipose Tissue-Mediated Vascular Tone. Frontiers in Physiology. 2021 Nov 26;12.

Published In

Frontiers in Physiology

DOI

EISSN

1664-042X

Publication Date

November 26, 2021

Volume

12

Related Subject Headings

  • 3208 Medical physiology
  • 3101 Biochemistry and cell biology
  • 1701 Psychology
  • 1116 Medical Physiology
  • 0606 Physiology