PMID- 33423309
OWN - NLM
STAT- MEDLINE
DCOM- 20210715
LR  - 20210715
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 35
IP  - 2
DP  - 2021 Feb
TI  - Deficiency of circadian gene cryptochromes in bone marrow-derived cells protects 
      against atherosclerosis in LDLR(-/-) mice.
PG  - e21309
LID - 10.1096/fj.202001818RRR [doi]
AB  - Cryptochromes are photoreceptors that mediate the circadian entrainment by light 
      in plants and animals. They are also involved in magnetic field sensing in some 
      animals. Recent studies suggest that cryptochromes play an essential role in 
      metabolism and cardiovascular disease. However, the tissue-specific function of 
      cryptochromes in atherosclerosis is unknown. We transplanted bone marrow from 
      wild-type (WT) and cryptochrome 1/2 knockout (Cry1/2 KO) mice into irradiated 
      recipient low-density lipoprotein receptor knockout (LDLR(-/-) ) mice and induced 
      atherosclerosis with a high cholesterol diet for 12 weeks. There was a reduction 
      in atherosclerotic plaques and macrophage accumulation in the aorta of LDLR(-/-) 
      mice that received Cry1/2 KO bone marrow compared to mice that received WT bone 
      marrow. Bone marrow-derived macrophages (BMDMs) from Cry1/2 KO mice exhibited 
      impaired uptake of low-density lipoprotein, and subsequently, impaired foam cell 
      formation. Analysis of macrophage mRNA circadian oscillations revealed that the 
      circadian rhythm of the LDLR mRNAs was lost in Cry1/2 KO BMDMs. Reinstalling the 
      circadian oscillatory LDLR mRNAs using adenovirus into the BMDMs was able to 
      rescue the lipid uptake and foam cell formation function. However, the 
      noncircadian oscillatory LDLR mRNAs exhibited reduced ability to rescue the 
      macrophage functions. These findings indicate that cryptochromes in bone 
      marrow-derived cells are critical mediators of atherosclerosis through regulation 
      of the LDLR mRNA circadian rhythm. Therapeutic measures targeting cryptochromes 
      in the macrophage may have important implications for atherosclerosis.
CI  - (c) 2021 Federation of American Societies for Experimental Biology.
FAU - Lin, Yu-Sheng
AU  - Lin YS
AUID- ORCID: 0000-0002-7654-6558
AD  - Healthcare Center, Chang Gung Memorial Hospital, Chang Gung University College of 
      Medicine, Taoyuan City, Taiwan.
AD  - Department of Cardiology, Chang Gung Memorial Hospital, Chang Gung University 
      College of Medicine, Taoyuan City, Taiwan.
FAU - Tsai, Ming-Lung
AU  - Tsai ML
AD  - Department of Cardiology, Chang Gung Memorial Hospital, Chang Gung University 
      College of Medicine, Taoyuan City, Taiwan.
FAU - Hsieh, I-Chang
AU  - Hsieh IC
AD  - Department of Cardiology, Chang Gung Memorial Hospital, Chang Gung University 
      College of Medicine, Taoyuan City, Taiwan.
FAU - Wen, Ming-Shien
AU  - Wen MS
AD  - Department of Cardiology, Chang Gung Memorial Hospital, Chang Gung University 
      College of Medicine, Taoyuan City, Taiwan.
FAU - Wang, Chao-Yung
AU  - Wang CY
AUID- ORCID: 0000-0003-1546-7298
AD  - Department of Cardiology, Chang Gung Memorial Hospital, Chang Gung University 
      College of Medicine, Taoyuan City, Taiwan.
AD  - Institute of Cellular and System Medicine, National Health Research Institutes, 
      Zhunan, Taiwan.
AD  - Department of Medical Science, National Tsing Hua University, Hsinchu, Taiwan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Cryptochromes)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, LDL)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - Animals
MH  - Atherosclerosis/genetics/*metabolism/*prevention & control
MH  - Bone Marrow Cells/*metabolism
MH  - Cells, Cultured
MH  - Cholesterol/blood
MH  - Cryptochromes/genetics/*metabolism
MH  - Female
MH  - Immunohistochemistry
MH  - Lipoproteins, LDL/genetics/metabolism
MH  - Macrophages, Peritoneal/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Plaque, Atherosclerotic/metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Receptors, LDL/*deficiency/genetics/*metabolism
OTO - NOTNLM
OT  - LDLR
OT  - atherosclerosis
OT  - circadian rhythm
OT  - cryptochrome
OT  - macrophages
EDAT- 2021/01/11 06:00
MHDA- 2021/07/16 06:00
CRDT- 2021/01/10 20:51
PHST- 2020/07/25 00:00 [received]
PHST- 2020/12/09 00:00 [revised]
PHST- 2020/12/11 00:00 [accepted]
PHST- 2021/01/10 20:51 [entrez]
PHST- 2021/01/11 06:00 [pubmed]
PHST- 2021/07/16 06:00 [medline]
AID - 10.1096/fj.202001818RRR [doi]
PST - ppublish
SO  - FASEB J. 2021 Feb;35(2):e21309. doi: 10.1096/fj.202001818RRR.