PMID- 35653618
OWN - NLM
STAT- MEDLINE
DCOM- 20220802
LR  - 20220816
IS  - 1743-5404 (Electronic)
IS  - 1743-5390 (Linking)
VI  - 16
IP  - 3
DP  - 2022 Apr
TI  - PM(2.5) induce the defective efferocytosis and promote atherosclerosis via HIF-1alpha 
      activation in macrophage.
PG  - 290-309
LID - 10.1080/17435390.2022.2083995 [doi]
AB  - Epidemiological studies demonstrate that fine particulate matter (PM(2.5)) 
      promotes the development of atherosclerosis. However, the mechanism insight of 
      PM(2.5)-induced atherosclerosis is still lacking. The aim of this study was to 
      explore the biological effects of hypoxia-inducible factor 1alpha (HIF-1alpha) on 
      PM(2.5)-triggered atherosclerosis. The vascular stiffness, carotid intima-media 
      thickness (CIMT), lipid and atherosclerotic lesion were increased when von 
      Hippel-Lindau (VHL)-null mice were exposed to PM(2.5). Yet, knockout of HIF-1alpha 
      markedly decreased the PM(2.5)-triggered atherosclerotic lesion. We firstly 
      performed microarray analysis in PM(2.5)-treated bone morrow-derived macrophages 
      (BMDMs), which showed that PM(2.5) significantly changed the genes expression 
      patterns and affected biological processes such as phagocytosis, apoptotic cell 
      clearance, cellular response to hypoxia, apoptotic process and inflammatory 
      response. Moreover, the data showed knockout of HIF-1alpha remarkably relieved 
      PM(2.5)-induced defective efferocytosis. Mechanistically, PM(2.5) inhibited the 
      level of genes and proteins of efferocytosis receptor c-Mer tyrosine kinase 
      (MerTK), especially in VHL-null BMDMs. In addition, PM(2.5) increased the genes 
      and proteins of a disintegrin and metallopeptidase domain 17 (ADAM17), which 
      caused the MerTK cleavage to form soluble MerTK (sMer) in plasma and cellular 
      supernatant. The sMer was significantly up-regulated in plasma of VHL-null 
      PM(2.5)-exposed mice. Moreover, PM(2.5) could induce defective efferocytosis and 
      activate inflammatory response through MerTK/IFNAR1/STAT1 signaling pathway in 
      macrophages. Our results demonstrate that PM(2.5) could induce defective 
      efferocytosis and inflammation by activating HIF-1alpha in macrophages, ultimately 
      resulting in accelerating atherosclerotic lesion formation and development. Our 
      data suggest HIF-1alpha in macrophages might be a potential target for 
      PM(2.5)-related atherosclerosis.
FAU - Liang, Shuang
AU  - Liang S
AD  - Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital 
      Medical University, Beijing, P.R. China.
AD  - Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, 
      Beijing, P.R. China.
FAU - Sun, Qinglin
AU  - Sun Q
AD  - Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital 
      Medical University, Beijing, P.R. China.
AD  - Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, 
      Beijing, P.R. China.
FAU - Du, Zhou
AU  - Du Z
AD  - Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital 
      Medical University, Beijing, P.R. China.
AD  - Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, 
      Beijing, P.R. China.
FAU - Ren, Xiaoke
AU  - Ren X
AD  - Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital 
      Medical University, Beijing, P.R. China.
AD  - Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, 
      Beijing, P.R. China.
FAU - Xu, Qing
AU  - Xu Q
AD  - Core Facility Centre, Capital Medical University, Beijing, P.R. China.
FAU - Sun, Zhiwei
AU  - Sun Z
AD  - Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital 
      Medical University, Beijing, P.R. China.
AD  - Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, 
      Beijing, P.R. China.
FAU - Duan, Junchao
AU  - Duan J
AD  - Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital 
      Medical University, Beijing, P.R. China.
AD  - Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, 
      Beijing, P.R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220602
PL  - England
TA  - Nanotoxicology
JT  - Nanotoxicology
JID - 101233132
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Particulate Matter)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (c-Mer Tyrosine Kinase)
SB  - IM
MH  - Animals
MH  - *Atherosclerosis/chemically induced/metabolism
MH  - *Carotid Intima-Media Thickness
MH  - Hypoxia/metabolism/pathology
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism
MH  - Macrophages
MH  - Mice
MH  - Particulate Matter/toxicity
MH  - Phagocytosis
MH  - Receptor Protein-Tyrosine Kinases/genetics/metabolism/pharmacology
MH  - c-Mer Tyrosine Kinase/metabolism
OTO - NOTNLM
OT  - Atherosclerosis
OT  - Bone morrow-derived macrophage
OT  - Efferocytosis
OT  - HIF-1alpha
OT  - PM2.5
EDAT- 2022/06/03 06:00
MHDA- 2022/08/03 06:00
CRDT- 2022/06/02 15:42
PHST- 2022/06/03 06:00 [pubmed]
PHST- 2022/08/03 06:00 [medline]
PHST- 2022/06/02 15:42 [entrez]
AID - 10.1080/17435390.2022.2083995 [doi]
PST - ppublish
SO  - Nanotoxicology. 2022 Apr;16(3):290-309. doi: 10.1080/17435390.2022.2083995. Epub 
      2022 Jun 2.