中文摘要：
尽管炎症在动脉粥样硬化的发展中发挥着关键作用，但其调节机制仍未理解。有报告称，血管周围脂肪组织（PVAT）在血管损伤后会发生炎症变化。在这里，我们显示血管损伤诱导PVAT的褐变（类似棕色脂肪组织的表型变化），这微调了炎症反应，从而作为保护机制促进血管重塑。在一种血管内损伤的小鼠模型中，巨噬细胞在PVAT中积累，导致褐变表型变化。通过基因沉默褐变的关键调节因子PRDM16，抑制PVAT的褐变，加重了损伤后的炎症和血管重塑。相反，激活PVAT的褐变则减轻了炎症和病理性血管重塑。单细胞RNA测序揭示，褐色脂肪细胞丰富地表达神经调节素4（Nrg4），它关键地调控替代巨噬细胞的活化。重要的是，在急性主动脉夹层患者的病变主动脉PVAT中观察到显著的褐变。综上所述，血管损伤诱导邻近PVAT的褐变与巨噬细胞的积累，其中褐色PVAT分泌的NRG4促进巨噬细胞的替代活化，导致血管炎症的消退。我们的研究表明PVAT在血管炎症和重塑中的关键作用，并将为治疗动脉粥样硬化开辟新的途径。
英文摘要：
Although inflammation plays critical roles in the development of atherosclerosis, its regulatory mechanisms remain incompletely understood. Perivascular adipose tissue (PVAT) has been reported to undergo inflammatory changes in response to vascular injury. Here, we show that vascular injury induces the beiging (brown adipose tissue-like phenotype change) of PVAT, which fine-tunes inflammatory response and thus vascular remodeling as a protective mechanism. In a mouse model of endovascular injury, macrophages accumulate in PVAT, causing beiging phenotype change. Inhibition of PVAT beiging by genetically silencing PRDM16, a key regulator to beiging, exacerbates inflammation and vascular remodeling following injury. Conversely, activation of PVAT beiging attenuates inflammation and pathological vascular remodeling. Single-cell RNA sequencing reveals that beige adipocytes abundantly express neuregulin 4 (Nrg4) which critically regulate alternative macrophage activation. Importantly, significant beiging is observed in the diseased aortic PVAT in patients with acute aortic dissection. Taken together, vascular injury induces the beiging of adjacent PVAT with macrophage accumulation, where NRG4 secreted from the beige PVAT facilitates alternative activation of macrophages, leading to the resolution of vascular inflammation. Our study demonstrates the pivotal roles of PVAT in vascular inflammation and remodeling and will open a new avenue for treating atherosclerosis.
论文信息：
论文题目：Beiging of perivascular adipose tissue regulates its inflammation and vascular remodeling
期刊名称：Nature Communications
时间期卷：13, Article number: 5117 (2022)
在线时间：2022年9月7日
DOI：doi.org/10.1038/s41467-022-32658-6
产品信息：
货号：CP-005-005
规格：5ml+5ml
品牌：Liposoma
产地：荷兰
名称：Clodronate Liposomes and Control Liposomes
办事处：Target Technology(靶点科技)
氯膦酸盐二钠脂质体清除单核巨噬细胞，在血管损伤诱导的炎性模型中单核巨噬细胞功能研究，荷兰Liposoma巨噬细胞清除剂Clodronate Liposomes见刊于Nature Communications：周围血管脂肪组织的肥大调节其炎症和血管重塑。
Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体的材料和方法：
To selectively remove the macrophages, mice were given intraperitoneally clodronate liposomes (200 μl/mouse) or control phosphate-buffered saline (PBS) liposomes (Liposoma BV) on the day of the endovascular injury and 7 days after injury.
材料和方法文献截图：
