Li Hsiao-Fen, Liu Hsin-Tzu, Chen Po-Yi, Lin Heng, Tseng Tzu-Ling
Department of Physiology, School of Medicine, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei, Taiwan.
Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 97004, Taiwan.
iScience. 2022 Nov 18;25(12):105631. doi: 10.1016/j.isci.2022.105631. eCollection 2022 Dec 22.
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.
胸主动脉血管周围脂肪组织（PVAT）是一种脂肪器官，在细胞形态和产热基因表达等方面与棕色脂肪组织（BAT）相似。然而，在生理血管系统中，PVAT表型是否与BAT表型无法区分仍不清楚。我们证明，鉴于PVAT具有特定的血管张力控制功能，它与经典的BAT是有区别的。激活转录因子3（ATF3）是高血压中的一个关键因素。与野生型小鼠相比，喂食高脂饮食的ATF3基因缺陷（ATF3 -/-）小鼠表现出平均动脉压升高、单核细胞趋化蛋白-1表达增加和肥大，以及胸主动脉PVAT中脂肪组织异常堆积，并且在离体主动脉环中氯化钾、U46619和去甲肾上腺素引起的血管壁张力增强和血管收缩反应增强，在给予腺相关ATF3载体后这些情况得以恢复。我们认为，调节肥胖相关血管功能障碍的是PVAT，而非BAT。PVAT中的ATF3可能为肥胖相关心血管疾病的病理生理学提供新的见解。
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