PMID- 33626512
OWN - NLM
STAT- MEDLINE
DCOM- 20210726
LR  - 20240226
IS  - 1945-4589 (Electronic)
IS  - 1945-4589 (Linking)
VI  - 13
IP  - 5
DP  - 2021 Feb 24
TI  - Nicotine exacerbates atherosclerosis through a macrophage-mediated endothelial 
      injury pathway.
PG  - 7627-7643
LID - 10.18632/aging.202660 [doi]
AB  - Evidence suggests that nicotine intake promotes atherosclerosis. We enrolled 100 
      patients with coronary heart disease (CHD) and found that plaque burden, TXNIP 
      expression, and inflammatory chemokine levels were higher in smokers than 
      non-smokers. Additionally, patients with higher TXNIP expression in peripheral 
      blood mononuclear cells (PBMCs) had a higher Gensini Scores and higher plasma 
      IL-1beta and IL-18 levels. Treating bone marrow-derived macrophages (BMDMs) with 
      nicotine in vitro led to enhanced lipid phagocytosis, chemotaxis, and increased 
      production of reactive oxygen species (ROS), which activated TXNIP/NLRP3 
      inflammasome signaling and promoted pyroptosis, as evidenced by caspase-1 
      cleavage and increased production of IL-1beta, IL-18, and gasdermin D. Nicotine 
      intake by ApoE((-/-)) mice fed a high-fat diet recapitulated those phenotypes. 
      The effects of nicotine on pyroptotic signaling were reversed by 
      N-acetyl-cysteine, a ROS scavenger. Silencing TXNIP in vivo reversed the effects 
      of nicotine on macrophage invasion and vascular injury. Nicotine also induced 
      pyroptotic macrophages that contributed to the apoptotic death of endothelial 
      cells. These findings suggest that nicotine accelerates atherosclerosis in part 
      by promoting macrophage pyroptosis and endothelial damage. Therefore, targeting 
      the TXNIP/NLRP3-mediated pyroptotic pathway in macrophages may ameliorate 
      nicotine-induced endothelial damage.
FAU - Mao, ChengYu
AU  - Mao C
AD  - Department of Cardiology, Ninth People's Hospital, Shanghai Jiao Tong University 
      School of Medicine, Shanghai 200011, People's Republic of China.
FAU - Li, DongJiu
AU  - Li D
AD  - Department of Cardiology, Ninth People's Hospital, Shanghai Jiao Tong University 
      School of Medicine, Shanghai 200011, People's Republic of China.
FAU - Zhou, En
AU  - Zhou E
AD  - Department of Cardiology, Ninth People's Hospital, Shanghai Jiao Tong University 
      School of Medicine, Shanghai 200011, People's Republic of China.
FAU - Zhang, JunFeng
AU  - Zhang J
AD  - Department of Cardiology, Ninth People's Hospital, Shanghai Jiao Tong University 
      School of Medicine, Shanghai 200011, People's Republic of China.
FAU - Wang, ChangQian
AU  - Wang C
AD  - Department of Cardiology, Ninth People's Hospital, Shanghai Jiao Tong University 
      School of Medicine, Shanghai 200011, People's Republic of China.
FAU - Xue, Chao
AU  - Xue C
AD  - Department of Cardiology, Ninth People's Hospital, Shanghai Jiao Tong University 
      School of Medicine, Shanghai 200011, People's Republic of China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210224
PL  - United States
TA  - Aging (Albany NY)
JT  - Aging
JID - 101508617
RN  - 0 (Carrier Proteins)
RN  - 0 (GSDMD protein, human)
RN  - 0 (Ganglionic Stimulants)
RN  - 0 (Inflammasomes)
RN  - 0 (Interleukin-18)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (NLRP3 protein, human)
RN  - 0 (Phosphate-Binding Proteins)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (TXNIP protein, human)
RN  - 6M3C89ZY6R (Nicotine)
SB  - IM
MH  - Animals
MH  - Carrier Proteins/*metabolism
MH  - Chemotaxis
MH  - Coronary Artery Disease/*metabolism
MH  - Female
MH  - Ganglionic Stimulants/pharmacology
MH  - Humans
MH  - Inflammasomes/metabolism
MH  - Interleukin-18/blood
MH  - Interleukin-1beta/blood
MH  - Intracellular Signaling Peptides and Proteins/metabolism
MH  - Macrophages/*drug effects
MH  - Male
MH  - Mice, Knockout
MH  - Middle Aged
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/genetics/metabolism
MH  - Nicotine/*pharmacology
MH  - Phagocytosis
MH  - Phosphate-Binding Proteins/metabolism
MH  - Pyroptosis/drug effects
MH  - Reactive Oxygen Species/metabolism
MH  - Severity of Illness Index
MH  - Signal Transduction/drug effects
MH  - Mice
PMC - PMC7993665
OTO - NOTNLM
OT  - endothelial injury
OT  - inflammasome
OT  - macrophages
OT  - nicotine
OT  - reactive oxygen species
COIS- CONFLICTS OF INTEREST: The authors declare that they have no known competing 
      financial interests or personal relationships that could have influenced the work 
      reported in this paper.
EDAT- 2021/02/25 06:00
MHDA- 2021/07/27 06:00
PMCR- 2021/03/15
CRDT- 2021/02/24 20:09
PHST- 2020/10/21 00:00 [received]
PHST- 2021/01/14 00:00 [accepted]
PHST- 2021/02/25 06:00 [pubmed]
PHST- 2021/07/27 06:00 [medline]
PHST- 2021/02/24 20:09 [entrez]
PHST- 2021/03/15 00:00 [pmc-release]
AID - 202660 [pii]
AID - 10.18632/aging.202660 [doi]
PST - ppublish
SO  - Aging (Albany NY). 2021 Feb 24;13(5):7627-7643. doi: 10.18632/aging.202660. Epub 
      2021 Feb 24.