Single-Cell RNA-Seq Reveals a Crosstalk between Hyaluronan Receptor LYVE-1-Expressing Macrophages and Vascular Smooth Muscle Cells.
Single-Cell RNA-Seq Reveals a Crosstalk between Hyaluronan Receptor LYVE-1-Expressing Macrophages and Vascular Smooth Muscle Cells.
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DOI：
10.3390/cells11030411
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发表时间：
2022-01-25
期刊：
影响因子：
6
通讯作者：
Miteva K
中科院分区：
文献类型：
--
作者：
Burger F;Baptista D;Roth A;Brandt KJ;da Silva RF;Montecucco F;Mach F;Miteva K
背景：动脉粥样硬化是一种慢性炎症性疾病，其中巨噬细胞参与疾病的进展。然而，在动脉粥样硬化的主动脉中的居民样巨噬细胞（res样）的作用并不完全清楚。研究方法：对接受正常胆固醇饮食（NCD）或高胆固醇饮食（HCD）的载脂蛋白E缺陷（Apoe−/−）小鼠的动脉粥样硬化主动脉中的CD 45+白细胞进行单细胞RNA测序分析，考虑动脉粥样硬化的侧特异性易感性。通过流式细胞术、共培养实验和免疫荧光法研究了颈动脉疾病（CAD）患者动脉粥样硬化斑块中表达透明质酸受体LYVE-1的res样巨噬细胞群。结果：我们确定了12个主要的白细胞簇与不同的动脉粥样硬化疾病相关的基因表达的签名。LYVE-1+ res样巨噬细胞表达高水平的CC基序趋化因子配体24（CCL 24，eotaxin-2），在Apoe−/−小鼠的高脂血症下扩增，并以CCL 24依赖性方式促进VSMC表型调节为成骨细胞/软骨细胞样细胞。此外，LYVE-1+ CCL 24+巨噬细胞的丰度和CCL 24的全身水平升高与血管钙化和CAD事件相关。结论：LYVE-1 res样巨噬细胞通过分泌CCL 24促进VSMC转分化为成骨样细胞，可能在血管钙化中起作用，并可能在动脉粥样硬化斑块不稳定中起有害作用。
Background: Atherosclerosis is a chronic inflammatory disease where macrophages participate in the progression of the disease. However, the role of resident-like macrophages (res-like) in the atherosclerotic aorta is not completely understood. Methods: A single-cell RNA sequencing analysis of CD45+ leukocytes in the atherosclerotic aorta of apolipoprotein E–deficient (Apoe−/−) mice on a normal cholesterol diet (NCD) or a high cholesterol diet (HCD), respecting the side-to-specific predisposition to atherosclerosis, was performed. A population of res-like macrophages expressing hyaluronan receptor LYVE-1 was investigated via flow cytometry, co-culture experiments, and immunofluorescence in human atherosclerotic plaques from carotid artery disease patients (CAD). Results: We identified 12 principal leukocyte clusters with distinct atherosclerosis disease-relevant gene expression signatures. LYVE-1+ res-like macrophages, expressing a high level of CC motif chemokine ligand 24 (CCL24, eotaxin-2), expanded under hypercholesteremia in Apoe−/− mice and promoted VSMC phenotypic modulation to osteoblast/chondrocyte-like cells, ex vivo, in a CCL24-dependent manner. Moreover, the abundance of LYVE-1+CCL24+ macrophages and elevated systemic levels of CCL24 were associated with vascular calcification and CAD events. Conclusions: LYVE-1 res-like macrophages, via the secretion of CCL24, promote the transdifferentiation of VSMC to osteogenic-like cells with a possible role in vascular calcification and likely a detrimental role in atherosclerotic plaque destabilization.
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影响因子：
4.6
作者：
Becker M;De Bastiani MA;Parisi MM;Guma FT;Markoski MM;Castro MA;Kaplan MH;Barbé-Tuana FM;Klamt F
通讯作者：
Klamt F
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
82.9
作者：
Gomez D;Baylis RA;Durgin BG;Newman AAC;Alencar GF;Mahan S;St Hilaire C;Müller W;Waisman A;Francis SE;Pinteaux E;Randolph GJ;Gram H;Owens GK
通讯作者：
Owens GK
影响因子：
7
作者：
Donato M;Xu Z;Tomoiaga A;Granneman JG;Mackenzie RG;Bao R;Than NG;Westfall PH;Romero R;Draghici S
通讯作者：
Draghici S
影响因子：
10.8
作者：
Durham AL;Speer MY;Scatena M;Giachelli CM;Shanahan CM
通讯作者：
Shanahan CM