TY - JOUR
T1 - Role of PVAT in obesity-related cardiovascular disease through the buffering activity of ATF3
AU - Li, Hsiao Fen
AU - Liu, Hsin Tzu
AU - Chen, Po Yi
AU - Lin, Heng
AU - Tseng, Tzu Ling
N1 - Funding Information:
The authors acknowledge the core facilities of the Advanced Instrumentation Center of the Department of Medicine Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Function, Hualien, Taiwan. The authors thank Editage ( https://www.editage.com.tw ) for English language editing. Funding: this work was supported by the Ministry of Science and Technology [ MOST 108-2314-B-038-048-MY3 to H Lin; MOST 110-2320-B-303-001-MY3 and MOST 111-2320-B-303-001 to TL Tseng], Buddhist Tzu Chi General Hospital Grant TCMMP ( 109-1 ) Taiwan to TL Tseng.
Funding Information:
The authors acknowledge the core facilities of the Advanced Instrumentation Center of the Department of Medicine Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Function, Hualien, Taiwan. The authors thank Editage (https://www.editage.com.tw) for English language editing. Funding: this work was supported by the Ministry of Science and Technology [MOST 108-2314-B-038-048-MY3 to H Lin; MOST 110-2320-B-303-001-MY3 and MOST 111-2320-B-303-001 to TL Tseng], Buddhist Tzu Chi General Hospital Grant TCMMP (109-1) Taiwan to TL Tseng. Conceptualization, T.L.T. and H.L.; Methodology, H.F.L. H.T.L. P.Y.C. and T.L.T.; Investigation, H.F.L. H.T.L. P.Y.C. and T.L.T.; Validation, T.L.T. and H.L.; Writing—Original Draft, T.L.T. and H.L.; Writing—Review & Editing, T.L.T. and H.L.; Project Administration, T.L.T. and H.L. The authors declare no competing interests.
Publisher Copyright:
© 2022 The Authors
PY - 2022/12/22
Y1 - 2022/12/22
N2 - 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.
AB - 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.
KW - Cardiovascular medicine
KW - Molecular biology
UR - http://www.scopus.com/inward/record.url?scp=85142853868&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85142853868&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2022.105631
DO - 10.1016/j.isci.2022.105631
M3 - Article
AN - SCOPUS:85142853868
SN - 2589-0042
VL - 25
JO - iScience
JF - iScience
IS - 12
M1 - 105631
ER -
