Role of PVAT in obesity-related cardiovascular disease through the buffering activity of ATF3

Hsiao-Fen Li; Hsin-Tzu Liu; Po-Yi Chen; Heng Lin; Tzu-Ling Tseng

doi:10.1016/j.isci.2022.105631

Role of PVAT in obesity-related cardiovascular disease through the buffering activity of ATF3

iScience. 2022 Nov 18;25(12):105631. doi: 10.1016/j.isci.2022.105631. eCollection 2022 Dec 22.

Authors

Hsiao-Fen Li¹, Hsin-Tzu Liu², Po-Yi Chen^{3

2}, Heng Lin^{1

4}, Tzu-Ling Tseng^{3

2

5}

Affiliations

¹ Department of Physiology, School of Medicine, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei, Taiwan.
² Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 97004, Taiwan.
³ CardioVascular Research Center Buddhist Tzu Chi Medical Foundation, No.707, Zhongyang Rd., Sec.3, Hualien 97004, Taiwan.
⁴ Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
⁵ Tzu Chi University of Science and Technology, Hualien, Taiwan.

Abstract

Thoracic aortic perivascular adipose tissue (PVAT) is an adipose organ exhibiting similarities to brown adipose tissue (BAT), including cellular morphology and thermogenic gene expression. However, whether the PVAT phenotype is indistinguishable from the BAT phenotype in physiological vasculature remains unclear. We demonstrated that PVAT is distinguishable from classical BAT, given its specific vessel-tone-controlling function. Activating transcription factor 3 (ATF3) is a key factor in hypertension. Compared with wild-type mice, ATF3-deficient (ATF3 ^-/- ) mice fed a high-fat diet exhibited elevated mean arterial pressure, increased monocyte chemoattractant protein-1 expression and hypertrophy, plus abnormal fatty tissue accumulation in the thoracic aortic PVAT, and enhanced vascular wall tension and vasoconstrictive responses of potassium chloride, U46619, and norepinephrine in isolated aortic rings, which were restored after administration of adeno-associated ATF3 vector. We suggest that PVAT, not BAT, modulates obesity-related vascular dysfunction. ATF3 within PVAT could provide new insights into the pathophysiology of obesity-related cardiovascular diseases.

Keywords: Cardiovascular medicine; Molecular biology.