Irie Daisuke, Kawahito Hiroyuki, Wakana Noriyuki, Kato Taku, Kishida Sou, Kikai Masakazu, Ogata Takehiro, Ikeda Koji, Ueyama Tomomi, Matoba Satoaki, Yamada Hiroyuki
Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Japan.
Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Japan
J Renin Angiotensin Aldosterone Syst. 2015 Mar;16(1):67-78. doi: 10.1177/1470320314552434. Epub 2014 Oct 16.
Perivascular adipose tissue is implicated in vasoreactivity; however, its effect on atherosclerosis remains undefined.
We examined the effect of a high-cholesterol diet (HCD) on phenotypic alterations of the thoracic periaortic adipose tissue (tPAT) in apoE-deficient (apoE(-/-)) mice. Gene expression of the components of the renin angiotensin system and that of macrophage markers were significantly higher in apoE(-/-) mice fed an HCD than in those fed a chow diet (CD). These changes were absent both in angiotensin II (AngII) receptor blocker (ARB)-treated apoE(-/-) mice and in Ang II type 1 (AT1) receptor-deficient apoE(-/-) (Agtr1(-/-)/apoE(-/-)) mice. To evaluate their effect on atherosclerosis, we transplanted tPAT into apoE(-/-) mice alongside the distal abdominal aorta. Transplanted tPAT was harvested from apoE(-/-) and Agtr1(-/-)/apoE(-/-) mice fed a CD (tPAT-CD/apoE(-/-), tPAT-CD/Agtr1(-/-)/apoE(-/-)), HCD (tPAT-HCD/apoE(-/-), tPAT-HCD/Agtr1(-/-)/apoE(-/-)), or HCD in combination with ARB treatment (tPAT-HCD/ARB/apoE(-/-)). Four weeks after transplantation, a significantly increased oil red O-positive area was observed in the aorta of tPAT-HCD/apoE(-/-) mice than in tPAT-CD/apoE(-/-) mice. Such a change was absent in tPAT-HCD/ARB/apoE(-/-) and tPAT-HCD/Agtr1(-/-)/apoE(-/-) mice.
Our findings demonstrated that AT1 receptor plays a crucial role in HCD-induced phenotypic alterations of tPAT, modulation of which could exert beneficial effects on atherosclerosis.
血管周围脂肪组织与血管反应性有关；然而，其对动脉粥样硬化的影响仍不明确。
我们研究了高胆固醇饮食（HCD）对载脂蛋白E缺陷（apoE(-/-)）小鼠胸主动脉周围脂肪组织（tPAT）表型改变的影响。喂食HCD的apoE(-/-)小鼠中，肾素血管紧张素系统成分和巨噬细胞标志物的基因表达显著高于喂食普通饮食（CD）的小鼠。在接受血管紧张素II（AngII）受体阻滞剂（ARB）治疗的apoE(-/-)小鼠和血管紧张素II 1型（AT1）受体缺陷的apoE(-/-)（Agtr1(-/-)/apoE(-/-)）小鼠中，这些变化均未出现。为了评估它们对动脉粥样硬化的影响，我们将tPAT移植到apoE(-/-)小鼠的腹主动脉远端。移植的tPAT取自喂食CD（tPAT-CD/apoE(-/-)，tPAT-CD/Agtr1(-/-)/apoE(-/-)）、HCD（tPAT-HCD/apoE(-/-)，tPAT-HCD/Agtr1(-/-)/apoE(-/-)）或HCD联合ARB治疗（tPAT-HCD/ARB/apoE(-/-)）的apoE(-/-)和Agtr1(-/-)/apoE(-/-)小鼠。移植后四周，与tPAT-CD/apoE(-/-)小鼠相比，tPAT-HCD/apoE(-/-)小鼠主动脉中油红O阳性面积显著增加。tPAT-HCD/ARB/apoE(-/-)和tPAT-HCD/Agtr1(-/-)/apoE(-/-)小鼠未出现这种变化。
我们的研究结果表明，AT1受体在HCD诱导的tPAT表型改变中起关键作用，调节该受体可能对动脉粥样硬化产生有益影响。
