PMID- 34393795
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210817
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 12
DP  - 2021
TI  - Atrial Natriuretic Peptide Inhibited ABCA1/G1-dependent Cholesterol Efflux 
      Related to Low HDL-C in Hypertensive Pregnant Patients.
PG  - 715302
LID - 10.3389/fphar.2021.715302 [doi]
LID - 715302
AB  - Objective: It has been reported that atrial natriuretic peptide (ANP) regulates 
      lipid metabolism by stimulating adipocyte browning, lipolysis, and lipid 
      oxidation, and by impacting the secretion of adipokines. In our previous study, 
      we found that the plasma ANP concentration of hypertensive disorders of pregnancy 
      (HDP) was significantly increased in comparison to that of normotensive pregnancy 
      patients. Thus, this study's objective was to investigate the lipid profile in 
      patients with HDP and determine the effects of ANP on the cholesterol efflux in 
      THP-1 macrophages. Methods: A total of 265 HDP patients and 178 normotensive 
      women as the control group were recruited. Clinical demographic characteristics 
      and laboratory profile data were collected. Plasma total triglycerides (TGs), 
      total cholesterol (TC), low-density cholesterol (LDL-C), and high-density 
      cholesterol (HDL-C) were compared between the two groups. THP-1 monocytes were 
      incubated with different concentrations of ANP. ATP-binding cassette transporter 
      A1 (ABCA1) and ATP-binding cassette transporter G1 (ABCG1) mRNA and protein were 
      evaluated. ABCA1- and ABCG1-mediated cholesterol efflux to apolipoprotein A-Ⅰ 
      (apoA-Ⅰ) and HDL, respectively, were measured by green fluorescent labeled NBD 
      cholesterol. Natriuretic peptide receptor A (NPR-A) siRNA and specific agonists 
      of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and liver X receptor 
      alpha (LXRalpha) were studied to investigate the mechanism involved. Results: Plasma TG, 
      TC, LDL-C, and LDL-C/HDL-C were significantly increased, and HDL-C was 
      significantly decreased in the HDP group in comparison to the control (all p < 
      0.001). ANP inhibited the expression of ABCA1 and ABCG1 at both the mRNA and 
      protein levels in a dose-dependent manner. The functions of ABCA1- and 
      ABCG1-mediated cholesterol efflux to apoA-I and HDL were significantly decreased. 
      NPR-A siRNA further confirmed that ANP binding to its receptor inhibited ABCA1/G1 
      expression through the PPAR-gamma/LXRalpha pathway. Conclusions: ABCA1/G1 was inhibited 
      by the stimulation of ANP when combined with NPR-A through the PPAR-gamma/LXRalpha 
      pathway in THP-1 macrophages. The ABCA1/G1-mediated cholesterol efflux was also 
      impaired by the stimulation of ANP. This may provide a new explanation for the 
      decreased level of HDL-C in HDP patients.
CI  - Copyright (c) 2021 Dong, Lin, Liu, Zhang, Jiang and Song.
FAU - Dong, Yubing
AU  - Dong Y
AD  - Department of Hypertension, The First Affiliated Hospital of Dalian Medical 
      University, DaLian, China.
FAU - Lin, Yi
AU  - Lin Y
AD  - Department of Hypertension, The First Affiliated Hospital of Dalian Medical 
      University, DaLian, China.
FAU - Liu, Wanyu
AU  - Liu W
AD  - Department of Hypertension, The First Affiliated Hospital of Dalian Medical 
      University, DaLian, China.
FAU - Zhang, Wei
AU  - Zhang W
AD  - Department of Hypertension, The First Affiliated Hospital of Dalian Medical 
      University, DaLian, China.
FAU - Jiang, Yinong
AU  - Jiang Y
AD  - Department of Hypertension, The First Affiliated Hospital of Dalian Medical 
      University, DaLian, China.
FAU - Song, Wei
AU  - Song W
AD  - Department of Hypertension, The First Affiliated Hospital of Dalian Medical 
      University, DaLian, China.
LA  - eng
PT  - Journal Article
DEP - 20210728
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC8355588
OTO - NOTNLM
OT  - ATP-binding cassette transporter A1
OT  - ATP-binding cassette transporter G1
OT  - atrial natriuretic peptide
OT  - cholesterol efflux
OT  - hypertensive disorders of pregnancy
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/08/17 06:00
MHDA- 2021/08/17 06:01
PMCR- 2021/07/28
CRDT- 2021/08/16 05:47
PHST- 2021/05/26 00:00 [received]
PHST- 2021/06/24 00:00 [accepted]
PHST- 2021/08/16 05:47 [entrez]
PHST- 2021/08/17 06:00 [pubmed]
PHST- 2021/08/17 06:01 [medline]
PHST- 2021/07/28 00:00 [pmc-release]
AID - 715302 [pii]
AID - 10.3389/fphar.2021.715302 [doi]
PST - epublish
SO  - Front Pharmacol. 2021 Jul 28;12:715302. doi: 10.3389/fphar.2021.715302. 
      eCollection 2021.