Deficient Chaperone-Mediated Autophagy Promotes Lipid Accumulation in Macrophage
| Autor: | Huixia Lu, Lei Qiao, Jie-qiong Peng, Jing Ma, Wenqiang Chen, Qiang Zhu, Sen Zhang, Yun Zhang, Hui Zheng, Dan Xu, Lei Xiang, He-feng Wang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Apolipoprotein E Chaperone-mediated autophagy Mice Knockout ApoE CD36 Pharmaceutical Science 03 medical and health sciences 0302 clinical medicine Lysosomal-Associated Membrane Protein 2 Coenzyme A Ligases Autophagy Genetics medicine Animals Macrophage Cells Cultured Genetics (clinical) biology Chemistry Lipid metabolism Sterol Esterase Atherosclerosis Lipid Metabolism Cell biology Mice Inbred C57BL Disease Models Animal 030104 developmental biology medicine.anatomical_structure ABCA1 Hepatocyte Lysosomal acid lipase Macrophages Peritoneal Long-chain-fatty-acid-CoA ligase 1 biology.protein Molecular Medicine Original Article lipids (amino acids peptides and proteins) Cardiology and Cardiovascular Medicine 030217 neurology & neurosurgery Oleic Acid |
| Zdroj: | Journal of Cardiovascular Translational Research |
| ISSN: | 1937-5395 1937-5387 |
| Popis: | Chaperone-mediated autophagy (CMA) serves as a critical upstream regulator of lipophagy and lipid metabolism in hepatocyte. However, the role of CMA in lipid metabolism of macrophage, the typical component of atherosclerotic plaque, remains unclear. In our study, LAMP-2A (L2A, a CMA marker) was reduced in macrophages exposed to high dose of oleate, and lipophagy was impaired in advanced atherosclerosis in ApoE (−/−) mice. Primary peritoneal macrophages isolated from macrophage-specific L2A-deficient mice exhibited pronounced intracellular lipid accumulation. Lipid regulatory enzymes, including long-chain-fatty-acid-CoA ligase 1 (ACSL1) and lysosomal acid lipase (LAL), were increased and reduced in L2A-KO macrophage, respectively. Other lipid-related proteins, such as SR-A, SR-B (CD36), ABCA1, or PLIN2, were not associated with increased lipid content in L2A-KO macrophage. In conclusion, deficient CMA promotes lipid accumulation in macrophage probably by regulating enzymes involved in lipid metabolism. CMA may represent a novel therapeutic target to alleviate atherosclerosis by promoting lipid metabolism. Graphical abstract Electronic supplementary material The online version of this article (10.1007/s12265-020-09986-3) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink