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大胞饮途径介导血管平滑肌细胞内脂滴聚集
Macropinocytosis mediates accumulation of lipid droplets in vascular smooth muscle cells
in vitro - 第三军医大学学报 2018年40卷第2期 页码：103-108
- 作者机构：
400042 重庆，陆军军医大学(第三军医大学)第三附属医院野战外科研究所神经内科
- 作者简介：
[张莉莉，E-mail：zll197312@hotmail.com ZHANG Lili, E-mail:zll197312@hotmail
- 基金信息：国家自然科学基金面上项目(81471193)
DOI：10.16016/j.1000-5404.201709029
中图分类号： R-332J;R363.21;R543.502收稿：2017-08-10，
修回：2017-11-10，
纸质出版：2018-01-30
- 稿件说明：
移动端阅览
陈雪, 王旭, 郭露, 等. 大胞饮途径介导血管平滑肌细胞内脂滴聚集[J]. 第三军医大学学报, 2018,40(2):103-108.
Xue CHEN, Xu WANG, Lu GUO, et al. Macropinocytosis mediates accumulation of lipid droplets in vascular smooth muscle cells
in vitro [J]. Journal of Third Military Medical University, 2018, 40(2): 103-108.陈雪, 王旭, 郭露, 等. 大胞饮途径介导血管平滑肌细胞内脂滴聚集[J]. 第三军医大学学报, 2018,40(2):103-108. DOI： 10.16016/j.1000-5404.201709029.
Xue CHEN, Xu WANG, Lu GUO, et al. Macropinocytosis mediates accumulation of lipid droplets in vascular smooth muscle cells
in vitro [J]. Journal of Third Military Medical University, 2018, 40(2): 103-108. DOI： 10.16016/j.1000-5404.201709029.
摘要
目的
2
探讨大胞饮途径是否介导血管平滑肌细胞(vascular smooth muscle cells，VSMCs)内脂滴聚集。
方法
2
组织块贴壁培养法培养VSMCs; 免疫荧光染色鉴定原代VSMCs; 天然低密度脂蛋白(nLDL，50、200、800 μg/mL)及脂多糖(LPS，200 ng/mL)刺激培养VSMCs，构建泡沫细胞模型; 流式细胞术检测VSMCs对大胞饮示踪剂Lucifer Yellow(LY)和DiI标记的nLDL(DiI-nLDL)的摄取; 油红O染色鉴定VSMCs内脂滴聚集。
结果
2
① LPS刺激可促进VSMCs对nLDL呈浓度依赖性地摄取增加，导致细胞内脂滴的聚集逐渐增多。②200 ng/mL LPS刺激VSMCs 6 h，VSMCs对LY的摄取增加75%(
P
<
0.01)，对DiI-nLDL的摄取增加76%(
P
<
0.01)。③应用胞饮抑制剂LY294002后，VSMCs对DiI-nLDL的摄取减少约29%(
P
<
0.01)，VSMCs内脂滴聚集明显减少。
结论
2
LPS刺激诱导VSMCs通过大胞饮途径摄取nLDL，从而增加细胞内脂滴的聚集，促进平滑肌源性泡沫细胞形成。
Abstract
Objective
2
To investigate whether macropinocytosis mediates the accumulation of lipid droplets in vascular smooth muscle cells (VSMCs).
Methods
2
Primary VSMCs were cultured with tissue explant method and identified by immunofluorescence staining. VSMCs-derived foam cells were induced by stimulation of the VSMCs with native low-density lipoprotein (nLDL) at 50
200
or 800 μg/mL and lipopolysaccharide (LPS) at 200 ng/mL. The changes in the uptake of Lucifer Yellow (LY) and DiI-nLDL by the VSMCs were assessed with flow cytometry.
Results
2
LPS promoted lipid droplet accumulation in nLDL-stimulated VSMCs in a concentration-dependent manner. The primary cultured VSMCs showed significantly increased LY uptake by 75% (
P
<
0.01) and DiI-nLDL uptake by 76% (
P
<
0.01) in response to stimulation with 200 ng/mL LPS for 6 h. The uptake of DiI-nLDL was significantly lowered by 29% (
P
<
0.01) and lipid droplet accumulation was significantly decreased in the cells after treatment with LY294002 for inhibiting macropinocytosis.
Conclusion
2
LPS induces the uptake of nLDL by VSMCs via the macropinocytosis pathway to promote the formation of VSMCs-derived foam cells.
关键词
Keywords
references
YU X H, FU Y C, ZHANG D W, et al .Foam cells in atherosclerosis[J ] .Clin Chim Acta, 2013, 424: 245-252.DOI: 10.1016/j.cca.2013.06.006.
MOORE K J, KUNJATHOOR V V, KOEHN S L, et al .Loss of receptor-mediated lipid uptake via scavenger receptor A or CD36 pathways does not ameliorate atherosclerosis in hyperlipidemic mice[J ] .J Clin Invest, 2005, 115(8): 2192-2201.DOI: 10.1172/JCI24061.
KRUTH H S, JONES N L, HUANG W, et al .Macropinocytosis is the endocytic pathway that mediates macrophage foam cell formation with native low density lipoprotein[J ] .J Biol Chem, 2005, 280(3): 2352-2360.DOI: 10.1074/jbc.M407167200.
KRUTH H S.Fluid-phase pinocytosis of LDL by macrophages: a novel target to reduce macrophage cholesterol accumulation in atherosclerotic lesions[J].Curr Pharm Des, 2013, 19(33): 5865-5872.DOI: 10.2174/1381612811319330005.
JOHNSON J L.Emerging regulators of vascular smooth muscle cell function in the development and progression of atherosclerosis[J].Cardiovasc Res, 2014, 103(4): 452-460.DOI: 10.1093/cvr/cvu171.
曹小洁, 张莉莉, 郭露, 等.oxLDL通过PPARγ-ABCG1通路促进血管平滑肌细胞泡沫化[J].第三军医大学学报, 2015, 37(4): 325-329.DOI: 10.16016/j.1000-540.201409084.CAO
X J, ZHANG L L, GUO L, et al .OxLDL promotes vascular smooth muscle cells to form foam cells through PPARγ-ABCG1 signal pathway[J ] .J Third Mil Med Univ, 2015, 37(4): 325-329.DOI: 10.16016/j.1000-540.201409084.
CHISTIAKOV D A, MELNICHENKO A A, OREKHOV A N, et al .How do macrophages sense modified low-density lipoproteins?[J ] .Int J Cardiol, 2017, 230: 232-240.DOI: 10.1016/j.ijcard.2016.12.164.
KRUTH H S.Receptor-independent fluid-phase pinocytosis mechanisms for induction of foam cell formation with native low-density lipoprotein particles[J].Curr Opin Lipidol, 2011, 22(5): 386-393.DOI: 10.1097/MOL.0b013e32834adadb.
JIANG D, YANG Y, LI D.Lipopolysaccharide induced vascular smooth muscle cells proliferation: A new potential therapeutic target for proliferative vascular diseases[J].Cell Prolif, 2017, 50(2): e12332.DOI: 10.1111/cpr.12332.
YIN Y W, LIAO S Q, ZHANG M J, et al .TLR4-mediated inflammation promotes foam cell formation of vascular smooth muscle cell by upregulating ACAT1 expression[J ] .Cell Death Dis, 2014, 5: e1574.DOI: 10.1038/cddis.2014.535.
GUO L, CHEN C H, ZHANG L L, et al .IRAK1 mediates TLR4-inducedABCA1 downregulation and lipid accumulation in VSMCs[J ] .Cell Death Dis, 2015, 6: e1949.DOI: 10.1038/cddis.2015.212.
BUCKLEY C M, KING J S.Drinking problems: mechanisms of macropinosome formation and maturation[J].FEBS J, 2017.DOI: 10.1111/febs.14115.
ZEINEDDINE R, YERBURY J J.The role of macropinocytosis in the propagation of protein aggregation associated with neurodegenerative diseases[J].Front Physiol, 2015, 6: 277.DOI: 10.3389/fphys.2015.00277.
ANZINGER J J, CHANG J, XU Q, et al .Murine bone marrow-derived macrophages differentiated with GM-CSF become foam cells by PI3Kgamma-dependent fluid-phase pinocytosis of native LDL[J ] .J Lipid Res, 2012, 53(1): 34-42.DOI: 10.1194/jlr.M018887.
DEMASI M, LAURINDO F R.Physiological and pathological role of the ubiquitin-proteasome system in the vascular smooth muscle cell[J].Cardiovasc Res, 2012, 95(2): 183-193.DOI: 10.1093/cvr/cvs128.
BOSEDASGUPTA S, PIETERS J.Inflammatory stimuli reprogram macrophage phagocytosis to macropinocytosis for the rapid elimination of pathogens[J].PLoS Pathog, 2014, 10(1): e1003879.DOI: 10.1371/journal.ppat.1003879.
MICHAEL D R, DAVIES T S, LAUBERTOVA L, et al .The phosphoinositide 3-kinase signaling pathway is involved in the control of modified low-density lipoprotein uptake by human macrophages[J ] .Lipids, 2015, 50(3): 253-260.DOI: 10.1007/s11745-015-3993-0.
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