PMID- 32285315
OWN - NLM
STAT- MEDLINE
DCOM- 20220202
LR  - 20240226
IS  - 1937-5395 (Electronic)
IS  - 1937-5387 (Print)
IS  - 1937-5387 (Linking)
VI  - 14
IP  - 4
DP  - 2021 Aug
TI  - Deficient Chaperone-Mediated Autophagy Promotes Lipid Accumulation in Macrophage.
PG  - 661-669
LID - 10.1007/s12265-020-09986-3 [doi]
AB  - 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.
CI  - (c) 2020. The Author(s).
FAU - Qiao, Lei
AU  - Qiao L
AD  - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese 
      Ministry of Education, Chinese National Health Commission and Chinese Academy of 
      Medical Sciences, The State and Shandong Province Joint Key Laboratory of 
      Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of 
      Shandong University, 107 Wenhuaxi Road, 250012, Jinan, China.
FAU - Wang, He-Feng
AU  - Wang HF
AD  - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese 
      Ministry of Education, Chinese National Health Commission and Chinese Academy of 
      Medical Sciences, The State and Shandong Province Joint Key Laboratory of 
      Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of 
      Shandong University, 107 Wenhuaxi Road, 250012, Jinan, China.
AD  - Qilu Hospital of Shandong University (Qingdao), No. 758 Hefei Road, Qingdao, 
      266035, China.
FAU - Xiang, Lei
AU  - Xiang L
AD  - Department of Cardiology, Sishui County People's Hospital, Sishui, 273200, 
      Shandong, China.
FAU - Ma, Jing
AU  - Ma J
AD  - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese 
      Ministry of Education, Chinese National Health Commission and Chinese Academy of 
      Medical Sciences, The State and Shandong Province Joint Key Laboratory of 
      Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of 
      Shandong University, 107 Wenhuaxi Road, 250012, Jinan, China.
FAU - Zhu, Qiang
AU  - Zhu Q
AD  - Department of clinical laboratory, Sishui County People's Hospital, Sishui, 
      273200, Shandong, China.
FAU - Xu, Dan
AU  - Xu D
AD  - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese 
      Ministry of Education, Chinese National Health Commission and Chinese Academy of 
      Medical Sciences, The State and Shandong Province Joint Key Laboratory of 
      Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of 
      Shandong University, 107 Wenhuaxi Road, 250012, Jinan, China.
FAU - Zheng, Hui
AU  - Zheng H
AD  - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese 
      Ministry of Education, Chinese National Health Commission and Chinese Academy of 
      Medical Sciences, The State and Shandong Province Joint Key Laboratory of 
      Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of 
      Shandong University, 107 Wenhuaxi Road, 250012, Jinan, China.
FAU - Peng, Jie-Qiong
AU  - Peng JQ
AD  - School of Medicine and Life Sciences, University of Jinan-Shandong Academy of 
      Medical Sciences, Jinan, China.
FAU - Zhang, Sen
AU  - Zhang S
AD  - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese 
      Ministry of Education, Chinese National Health Commission and Chinese Academy of 
      Medical Sciences, The State and Shandong Province Joint Key Laboratory of 
      Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of 
      Shandong University, 107 Wenhuaxi Road, 250012, Jinan, China.
AD  - Qilu Hospital of Shandong University (Qingdao), No. 758 Hefei Road, Qingdao, 
      266035, China.
FAU - Lu, Hui-Xia
AU  - Lu HX
AD  - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese 
      Ministry of Education, Chinese National Health Commission and Chinese Academy of 
      Medical Sciences, The State and Shandong Province Joint Key Laboratory of 
      Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of 
      Shandong University, 107 Wenhuaxi Road, 250012, Jinan, China.
FAU - Chen, Wen-Qiang
AU  - Chen WQ
AD  - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese 
      Ministry of Education, Chinese National Health Commission and Chinese Academy of 
      Medical Sciences, The State and Shandong Province Joint Key Laboratory of 
      Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of 
      Shandong University, 107 Wenhuaxi Road, 250012, Jinan, China. 
      199262000802@sdu.edu.cn.
FAU - Zhang, Yun
AU  - Zhang Y
AD  - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese 
      Ministry of Education, Chinese National Health Commission and Chinese Academy of 
      Medical Sciences, The State and Shandong Province Joint Key Laboratory of 
      Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of 
      Shandong University, 107 Wenhuaxi Road, 250012, Jinan, China. 
      zhangyun@sdu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200413
PL  - United States
TA  - J Cardiovasc Transl Res
JT  - Journal of cardiovascular translational research
JID - 101468585
RN  - 0 (LAMP2 protein, human)
RN  - 0 (Lysosomal-Associated Membrane Protein 2)
RN  - 2UMI9U37CP (Oleic Acid)
RN  - EC 3.1.1.13 (Sterol Esterase)
RN  - EC 3.1.1.13 (lysosomal acid lipase, mouse)
RN  - EC 6.2.1.- (ACSL1 protein, mouse)
RN  - EC 6.2.1.- (Coenzyme A Ligases)
SB  - IM
MH  - Animals
MH  - Atherosclerosis/genetics/*metabolism/pathology
MH  - *Autophagy/drug effects
MH  - Cells, Cultured
MH  - Coenzyme A Ligases/metabolism
MH  - Disease Models, Animal
MH  - *Lipid Metabolism/drug effects
MH  - Lysosomal-Associated Membrane Protein 2/genetics/*metabolism
MH  - Macrophages, Peritoneal/drug effects/*metabolism/pathology
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout, ApoE
MH  - Oleic Acid/toxicity
MH  - Sterol Esterase/metabolism
MH  - Mice
PMC - PMC8397667
OTO - NOTNLM
OT  - Atherosclerosis
OT  - Chaperone-mediated autophagy
OT  - Lipid metabolism
OT  - Long-chain-fatty-acid-CoA ligase 1
OT  - Lysosomal acid lipase
COIS- The authors declare that they have no conflict of interest.
EDAT- 2020/04/15 06:00
MHDA- 2022/02/03 06:00
PMCR- 2020/04/13
CRDT- 2020/04/15 06:00
PHST- 2020/01/14 00:00 [received]
PHST- 2020/03/06 00:00 [accepted]
PHST- 2020/04/15 06:00 [pubmed]
PHST- 2022/02/03 06:00 [medline]
PHST- 2020/04/15 06:00 [entrez]
PHST- 2020/04/13 00:00 [pmc-release]
AID - 10.1007/s12265-020-09986-3 [pii]
AID - 9986 [pii]
AID - 10.1007/s12265-020-09986-3 [doi]
PST - ppublish
SO  - J Cardiovasc Transl Res. 2021 Aug;14(4):661-669. doi: 10.1007/s12265-020-09986-3. 
      Epub 2020 Apr 13.