PMID- 34912234
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240404
IS  - 1664-042X (Print)
IS  - 1664-042X (Electronic)
IS  - 1664-042X (Linking)
VI  - 12
DP  - 2021
TI  - Antiphospholipid Antibodies From Women With Pregnancy Morbidity and Vascular 
      Thrombosis Induce Endothelial Mitochondrial Dysfunction, mTOR Activation, and 
      Autophagy.
PG  - 706743
LID - 10.3389/fphys.2021.706743 [doi]
LID - 706743
AB  - Antiphospholipid syndrome (APS) is an autoimmune disease characterized by 
      thrombosis and pregnancy morbidity (PM) obstetric events together with persistent 
      high titers of circulating antiphospholipid antibodies (aPL). Several mechanisms 
      that explain the development of thrombosis and PM in APS include the association 
      of aPL with alterations in the coagulation cascade and inflammatory events. Other 
      mechanisms disturbing cellular homeostases, such as mitochondrial dysfunction, 
      autophagy, and cell proliferation, have been described in other autoimmune 
      diseases. Therefore, the objective of this study was to investigate the impact of 
      aPL from different patient populations on endothelial cell mitochondrial 
      function, activation of the mammalian target of rapamycin (mTOR) and autophagy 
      pathways, and cellular growth. Using an in vitro model, human umbilical vein 
      endothelial cells (HUVECs) were treated with polyclonal immunoglobulin G (IgG) 
      purified from the serum of women with both PM and vascular thrombosis (PM/VT), 
      with VT only (VT), or with PM and non-criteria aPL (seronegative-obstetric APS, 
      SN-OAPS). We included IgG from women with PM without aPL (PM/aPL-) and healthy 
      women with previous uncomplicated pregnancies (normal human serum, NHS) as 
      control groups. Mitochondrial function, mTOR activation, autophagy, and cell 
      proliferation were evaluated by Western blotting, flow cytometry, and functional 
      assays. IgG from women with PM/VT increased HUVEC mitochondrial hyperpolarization 
      and activation of the mTOR and autophagic pathways, while IgG from patients with 
      VT induced endothelial autophagy and cell proliferation in the absence of 
      elevated mTOR activity or mitochondrial dysfunction. IgG from the SN-OAPS patient 
      group had no effect on any of these HUVEC responses. In conclusion, aPL from 
      women with PM and vascular events induce cellular stress evidenced by 
      mitochondrial hyperpolarization and increased activation of the mTOR and 
      autophagic pathways which may play a role in the pathogenesis of obstetric APS.
CI  - Copyright (c) 2021 Rodriguez, Velasquez-Berrio, Rua, Viana, Abrahams, Cadavid and 
      Alvarez.
FAU - Rodriguez, Carlos M
AU  - Rodriguez CM
AD  - Grupo Reproduccion, Facultad de Medicina, Departamento de Microbiologia y 
      Parasitologia, Universidad de Antioquia (UdeA), Medellin, Colombia.
FAU - Velasquez-Berrio, Manuela
AU  - Velasquez-Berrio M
AD  - Grupo Reproduccion, Facultad de Medicina, Departamento de Microbiologia y 
      Parasitologia, Universidad de Antioquia (UdeA), Medellin, Colombia.
FAU - Rua, Carolina
AU  - Rua C
AD  - Grupo de Investigacion en Trombosis, Facultad de Medicina, Universidad de 
      Antioquia (UdeA), Medellin, Colombia.
FAU - Viana, Marta
AU  - Viana M
AD  - Grupo de Metabolismo y Funcion Vascular, Departamento de Quimica y Bioquimica, 
      Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Madrid, Spain.
AD  - Red Iberoamericana de Alteraciones Vasculares Asociadas a Transtornos del 
      Embarazo (RIVATREM), Chillan, Chile.
FAU - Abrahams, Vikki M
AU  - Abrahams VM
AD  - Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of 
      Medicine, New Haven, CT, United States.
FAU - Cadavid, Angela P
AU  - Cadavid AP
AD  - Grupo Reproduccion, Facultad de Medicina, Departamento de Microbiologia y 
      Parasitologia, Universidad de Antioquia (UdeA), Medellin, Colombia.
AD  - Red Iberoamericana de Alteraciones Vasculares Asociadas a Transtornos del 
      Embarazo (RIVATREM), Chillan, Chile.
FAU - Alvarez, Angela M
AU  - Alvarez AM
AD  - Grupo Reproduccion, Facultad de Medicina, Departamento de Microbiologia y 
      Parasitologia, Universidad de Antioquia (UdeA), Medellin, Colombia.
LA  - eng
PT  - Journal Article
DEP - 20211129
PL  - Switzerland
TA  - Front Physiol
JT  - Frontiers in physiology
JID - 101549006
PMC - PMC8667788
OTO - NOTNLM
OT  - antiphospholipid antibodies
OT  - antiphospholipid syndrome
OT  - autophagy
OT  - endothelial cell
OT  - mTOR
OT  - mitochondria
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- 2021/12/17 06:00
MHDA- 2021/12/17 06:01
PMCR- 2021/11/29
CRDT- 2021/12/16 06:30
PHST- 2021/05/07 00:00 [received]
PHST- 2021/10/18 00:00 [accepted]
PHST- 2021/12/16 06:30 [entrez]
PHST- 2021/12/17 06:00 [pubmed]
PHST- 2021/12/17 06:01 [medline]
PHST- 2021/11/29 00:00 [pmc-release]
AID - 10.3389/fphys.2021.706743 [doi]
PST - epublish
SO  - Front Physiol. 2021 Nov 29;12:706743. doi: 10.3389/fphys.2021.706743. eCollection 
      2021.