Age-associated adipose tissue inflammation promotes monocyte chemotaxis and enhances atherosclerosis.
Age-associated adipose tissue inflammation promotes monocyte chemotaxis and enhances atherosclerosis.
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与年龄相关的脂肪组织炎症促进单核细胞趋化性并增强动脉粥样硬化。
作者：
尽管衰老会加剧动脉粥样硬化，但我们不知道这是否是通过循环免疫细胞、脂质代谢、脉管系统或脂肪组织的改变而发生的。在这里，我们研究了衰老是否对小鼠的脂肪组织产生直接的促动脉粥样硬化作用。在证明衰老会增强内脏脂肪组织而非皮下脂肪组织的炎症特征后，我们将年轻或老年小鼠的内脏脂肪移植到 Ldlr -/− 受体的右颈动脉上。老化的脂肪移植不仅增加了动脉粥样硬化斑块的大小，并增加了邻近颈动脉中的巨噬细胞数量，而且还增加了远端血管区域的巨噬细胞数量，这表明脂肪组织的老化通过分泌因子增强了动脉粥样硬化。通过消耗内脏脂肪中的巨噬细胞，我们发现脂肪组织巨噬细胞是分泌因子的主要贡献者。为了识别这些炎症因子，我们发现老化的脂肪移植物分泌的炎症介质 TNFα、CXCL2 和 CCL2 水平升高，这些介质协同促进单核细胞趋化性。重要的是，这些炎症介质的联合阻断阻碍了老化脂肪移植增强动脉粥样硬化的能力。总之，我们的研究表明，衰老通过增加内脏脂肪炎症而加剧动脉粥样硬化。我们的研究表明，未来针对内脏脂肪的疗法可能会减轻不断扩大的老年人口中的动脉粥样硬化疾病负担。衰老会增加内脏脂肪炎症，包括脂肪组织巨噬细胞（MΦ）的增加。老化内脏脂肪中的巨噬细胞分泌增加的炎症介质，特别是 TNFα、CCL2 和 CXCL2，从而促进循环单核细胞的动脉粥样硬化表型。单核细胞炎症标志物、趋化因子受体和迁移相关基因的表达增加，从而导致单核细胞向动脉壁迁移增强，从而促进动脉粥样硬化形成。
Although aging enhances atherosclerosis, we do not know if this occurs via alterations in circulating immune cells, lipid metabolism, vasculature, or adipose tissue. Here, we examined whether aging exerts a direct pro‐atherogenic effect on adipose tissue in mice. After demonstrating that aging augmented the inflammatory profile of visceral but not subcutaneous adipose tissue, we transplanted visceral fat from young or aged mice onto the right carotid artery of Ldlr −/− recipients. Aged fat transplants not only increased atherosclerotic plaque size with increased macrophage numbers in the adjacent carotid artery, but also in distal vascular territories, indicating that aging of the adipose tissue enhances atherosclerosis via secreted factors. By depleting macrophages from the visceral fat, we identified that adipose tissue macrophages are major contributors of the secreted factors. To identify these inflammatory factors, we found that aged fat transplants secreted increased levels of the inflammatory mediators TNFα, CXCL2, and CCL2, which synergized to promote monocyte chemotaxis. Importantly, the combined blockade of these inflammatory mediators impeded the ability of aged fat transplants to enhance atherosclerosis. In conclusion, our study reveals that aging enhances atherosclerosis via increased inflammation of visceral fat. Our study suggests that future therapies targeting the visceral fat may reduce atherosclerosis disease burden in the expanding older population. Aging increases visceral fat inflammation including the increase of adipose tissue macrophages (MΦ). The macrophages in aged visceral fat then secrete increased inflammatory mediators specifically TNFα, CCL2 and CXCL2, which consequently promote an atherogenic phenotype on circulating monocytes. The monocytes gain increased expression of inflammatory markers, chemokine receptors and migration related genes, which leads to enhanced migration of monocytes towards the artery wall to promote atherogenesis.
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影响因子：
64.5
作者：
López-Otín C;Blasco MA;Partridge L;Serrano M;Kroemer G
通讯作者：
Kroemer G
DOI：
10.1161/atvbaha.114.303983
发表时间：
2014-08
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Manka D;Chatterjee TK;Stoll LL;Basford JE;Konaniah ES;Srinivasan R;Bogdanov VY;Tang Y;Blomkalns AL;Hui DY;Weintraub NL
通讯作者：
Weintraub NL
影响因子：
4
作者：
Chen P;Parks WC
通讯作者：
Parks WC
影响因子：
7.7
作者：
Lumeng, Carey N.;DeYoung, Stephanie M.;Saltiel, Alan R.
通讯作者：
Saltiel, Alan R.
DOI：
10.1038/nri3520
发表时间：
2013-10
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
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