Loss of perivascular adipose tissue on peroxisome proliferator-activated receptor-γ deletion in smooth muscle cells impairs intravascular thermoregulation and enhances atherosclerosis.
Loss of perivascular adipose tissue on peroxisome proliferator-activated receptor-γ deletion in smooth muscle cells impairs intravascular thermoregulation and enhances atherosclerosis.
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DOI：
10.1161/circulationaha.112.104489
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发表时间：
2012-08-28
期刊：
影响因子：
37.8
通讯作者：
Chen YE
中科院分区：
文献类型：
--
作者：
Chang L;Villacorta L;Li R;Hamblin M;Xu W;Dou C;Zhang J;Wu J;Zeng R;Chen YE
血管周围脂肪组织（PVAT）围绕大多数血管，与棕色脂肪组织（BAT）具有共同特征。尽管BAT中的适应性产热增加能量消耗并且对代谢疾病有益，但对PVAT在血管疾病如动脉粥样硬化中的作用知之甚少。我们推测PVAT的产热功能调节血管内温度并减少动脉粥样硬化。PVAT与BAT具有相似的结构和蛋白质组学。我们证明PVAT在体内对冷刺激的反应中具有与BAT相似的产热特性。蛋白质组学分析的PVAT从小鼠居住在寒冷的环境中确定差异表达的蛋白质高度相关的细胞代谢过程。在平滑肌细胞中缺乏PPARγ的小鼠模型（SMPG KO小鼠）中，我们发现血管系统周围完全不存在PVAT，这可能是由于血管周围脂肪细胞前体细胞中也存在PPARγ缺失。缺乏PVAT，导致其产热活性丧失，损害血管稳态，引起温度损失和内皮功能障碍。我们进一步表明，冷暴露抑制动脉粥样硬化和改善内皮功能的小鼠与完整的PVAT，但不是在SMPG基因敲除小鼠，由于受损的脂质清除。PVAT中的促炎细胞因子表达在冷暴露后不改变。最后，从PVAT释放的前列环素有助于血管保护免受内皮功能障碍。PVAT是一种血管活性器官，其功能特征与BAT相似，并且在冷适应后对血管内温度调节至关重要。PVAT的这种产热能力在动脉粥样硬化的发病机制中起着重要的保护作用。
Perivascular adipose tissue (PVAT) surrounds most vessels and shares common features with brown adipose tissue (BAT). Whereas adaptive thermogenesis in BAT increases energy expenditure and is beneficial for metabolic diseases, little is known on the role of PVAT in vascular diseases such as atherosclerosis. We hypothesize that the thermogenic function of PVAT regulates intravascular temperature and reduces atherosclerosis. PVAT shares similar structural and proteomics with BAT. We demonstrate that PVAT has thermogenic properties similar to BAT in response to cold stimuli in vivo. Proteomics analysis of the PVAT from mice housed in a cold environment identified differential expression in proteins highly related with cellular metabolic processes. In a mouse model deficient in PPARγ in smooth muscle cells (SMPG KO mice), we uncovered a complete absence of PVAT surrounding the vasculature likely due to PPARγ deletion also in the perivascular adipocyte precursor cells. Lack of PVAT, resulting in loss of its thermogenic activity, impairs vascular homeostasis causing temperature loss and endothelial dysfunction. We further show that cold exposure inhibits atherosclerosis and improves endothelial function in mice with intact PVAT, but not in SMPG KO mice, as a result of impaired lipid clearance. Pro-inflammatory cytokine expression in PVAT is not altered upon cold exposure. Finally, prostacyclin released from PVAT contributes to the vascular protection against endothelial dysfunction. PVAT is a vasoactive organ with functional characteristics similar to BAT and is essential for intravascular thermoregulation upon cold acclimation. This thermogenic capacity of PVAT plays an important protective role in the pathogenesis of atherosclerosis.