PMID- 32856035
OWN - NLM
STAT- MEDLINE
DCOM- 20210323
LR  - 20210323
IS  - 1470-8736 (Electronic)
IS  - 0143-5221 (Linking)
VI  - 134
IP  - 17
DP  - 2020 Sep 18
TI  - High-cholesterol diet during pregnancy induces maternal vascular dysfunction in 
      mice: potential role for oxidized LDL-induced LOX-1 and AT1 receptor activation.
PG  - 2295-2313
LID - 10.1042/CS20200764 [doi]
AB  - The lectin-like oxidized low-density-lipoprotein (oxLDL) receptor-1 (LOX-1) has 
      been shown to induce angiotensin II (AngII) type 1 receptor (AT1) activation, 
      contributing to vascular dysfunction. Preeclampsia is a pregnancy complication 
      characterized by vascular dysfunction and increased LOX-1 and AT1 activation; 
      however, whether LOX-1 and AT1 activity contributes to vascular dysfunction in 
      preeclampsia is unknown. We hypothesized that increased oxLDL levels during 
      pregnancy lead to LOX-1 activation and subsequent AT1 activation, resulting in 
      vascular dysfunction. Pregnant wild-type (WT) and transgenic LOX-1 overexpressing 
      (LOX-1tg) mice were fed a control diet (CD) or high-cholesterol diet (HCD, to 
      impair vascular function) between gestational day (GD) 13.5-GD18.5. On GD18.5, 
      AngII-induced vasoconstriction and methylcholine (MCh)-induced 
      endothelium-dependent vasodilation responses were assessed in aortas and uterine 
      arteries. HCD decreased fetal weight and increased circulating oxLDL/cholesterol 
      levels in WT, but not in LOX-1tg mice. HCD did not alter AngII responsiveness or 
      AT1 expression in both vascular beds; however, AngII responsiveness and AT1 
      expression were lower in aortas from LOX-1tg compared with WT mice. In aortas 
      from WT-CD mice, acute oxLDL exposure induced AT1-mediated vasoconstriction via 
      LOX-1. HCD impaired endothelium-dependent vasodilation and increased superoxide 
      levels in WT aortas, but not uterine arteries. Moreover, in WT-CD mice oxLDL 
      decreased MCh sensitivity in both vascular beds, partially via LOX-1. In summary, 
      HCD impaired pregnancy outcomes and vascular function, and oxLDL-induced LOX-1 
      activation may contribute to vascular dysfunction via AT1. Our study suggests 
      that LOX-1 could be a potential target to prevent adverse outcomes associated 
      with vascular dysfunction in preeclampsia.
CI  - (c) 2020 The Author(s). Published by Portland Press Limited on behalf of the 
      Biochemical Society.
FAU - Saez, Tamara
AU  - Saez T
AD  - Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Canada.
AD  - Women and Children's Health Research Institute, University of Alberta, Edmonton, 
      Canada.
FAU - Spaans, Floor
AU  - Spaans F
AD  - Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Canada.
AD  - Women and Children's Health Research Institute, University of Alberta, Edmonton, 
      Canada.
FAU - Kirschenman, Raven
AU  - Kirschenman R
AD  - Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Canada.
AD  - Women and Children's Health Research Institute, University of Alberta, Edmonton, 
      Canada.
FAU - Sawamura, Tatsuya
AU  - Sawamura T
AD  - Departments of Molecular Pathophysiology and Life Innovation, Shinshu University, 
      Matsumoto, Japan.
FAU - Davidge, Sandra T
AU  - Davidge ST
AD  - Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Canada.
AD  - Women and Children's Health Research Institute, University of Alberta, Edmonton, 
      Canada.
AD  - Department of Physiology, University of Alberta, Edmonton, Canada.
LA  - eng
GR  - MOP142320/CIHR/Canada
GR  - FS154313/CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Clin Sci (Lond)
JT  - Clinical science (London, England : 1979)
JID - 7905731
RN  - 0 (Cholesterol, Dietary)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - 0 (Scavenger Receptors, Class E)
RN  - 0 (methylcholine)
RN  - 0 (oxidized low density lipoprotein)
RN  - 11062-77-4 (Superoxides)
RN  - 11128-99-7 (Angiotensin II)
RN  - N91BDP6H0X (Choline)
SB  - IM
MH  - Angiotensin II
MH  - Animals
MH  - Aorta/drug effects/pathology/physiopathology
MH  - Body Weight/drug effects
MH  - Cholesterol, Dietary
MH  - Choline/analogs & derivatives
MH  - Endothelium, Vascular/drug effects/pathology/physiopathology
MH  - Female
MH  - Fetus/drug effects/pathology
MH  - Lipoproteins, LDL/*pharmacology
MH  - Mice, Transgenic
MH  - Oxidative Stress/drug effects
MH  - Pregnancy
MH  - Receptor, Angiotensin, Type 1/*metabolism
MH  - Scavenger Receptors, Class E/*metabolism
MH  - Superoxides/metabolism
MH  - Uterine Artery/pathology/physiopathology
MH  - Vascular Diseases/pathology/*physiopathology
MH  - Vasoconstriction/drug effects
MH  - Vasodilation/drug effects
OTO - NOTNLM
OT  - AT1
OT  - LOX-1
OT  - high-cholesterol diet
OT  - oxidized LDL
OT  - preeclampsia
OT  - vascular dysfunction
EDAT- 2020/08/29 06:00
MHDA- 2021/03/24 06:00
CRDT- 2020/08/29 06:00
PHST- 2020/06/03 00:00 [received]
PHST- 2020/08/17 00:00 [revised]
PHST- 2020/08/26 00:00 [accepted]
PHST- 2020/08/29 06:00 [pubmed]
PHST- 2021/03/24 06:00 [medline]
PHST- 2020/08/29 06:00 [entrez]
AID - 226203 [pii]
AID - 10.1042/CS20200764 [doi]
PST - ppublish
SO  - Clin Sci (Lond). 2020 Sep 18;134(17):2295-2313. doi: 10.1042/CS20200764.