氯膦酸二鈉脂質(zhì)體在血管損傷模型清除巨噬細胞功能研究

中文摘要：

盡管炎癥在動脈粥樣硬化的發(fā)展中發(fā)揮著關(guān)鍵作用，但其調(diào)節(jié)機制仍未理解。有報告稱，血管周圍脂肪組織（PVAT）在血管損傷后會發(fā)生炎癥變化。在這里，我們顯示血管損傷誘導(dǎo)PVAT的褐變（類似棕色脂肪組織的表型變化），這微調(diào)了炎癥反應(yīng)，從而作為保護機制促進血管重塑。在一種血管內(nèi)損傷的小鼠模型中，巨噬細胞在PVAT中積累，導(dǎo)致褐變表型變化。通過基因沉默褐變的關(guān)鍵調(diào)節(jié)因子PRDM16，抑制PVAT的褐變，加重了損傷后的炎癥和血管重塑。相反，激活PVAT的褐變則減輕了炎癥和病理性血管重塑。單細胞RNA測序揭示，褐色脂肪細胞豐富地表達神經(jīng)調(diào)節(jié)素4（Nrg4），它關(guān)鍵地調(diào)控替代巨噬細胞的活化。重要的是，在急性主動脈夾層患者的病變主動脈PVAT中觀察到顯著的褐變。綜上所述，血管損傷誘導(dǎo)鄰近PVAT的褐變與巨噬細胞的積累，其中褐色PVAT分泌的NRG4促進巨噬細胞的替代活化，導(dǎo)致血管炎癥的消退。我們的研究表明PVAT在血管炎癥和重塑中的關(guān)鍵作用，并將為治療動脈粥樣硬化開辟新的途徑。

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.

論文信息：

論文題目：Beiging of perivascular adipose tissue regulates its inflammation and vascular remodeling

期刊名稱：Nature Communications

時間期卷：13, Article number: 5117 (2022)

在線時間：2022年9月7日

DOI：doi.org/10.1038/s41467-022-32658-6

產(chǎn)品信息：

貨號：CP-005-005

規(guī)格：5ml+5ml

品牌：Liposoma

產(chǎn)地：荷蘭

名稱：Clodronate Liposomes and Control Liposomes

辦事處：Target Technology(靶點科技)

氯膦酸鹽二鈉脂質(zhì)體清除單核巨噬細胞，在血管損傷誘導(dǎo)的炎性模型中單核巨噬細胞功能研究，荷蘭Liposoma巨噬細胞清除劑Clodronate Liposomes見刊于Nature Communications：周圍血管脂肪組織的肥大調(diào)節(jié)其炎癥和血管重塑。

Liposoma巨噬細胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)體的材料和方法：

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.

材料和方法文獻截圖：