PMID- 26461397
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20160301
LR  - 20151014
IS  - 1873-4596 (Electronic)
IS  - 0891-5849 (Linking)
VI  - 75 Suppl 1
DP  - 2014 Oct
TI  - Control of endothelial function and angiogenesis by PGC-1alpha relies on ROS control 
      of vascular stability.
PG  - S5
LID - S0891-5849(14)01337-9 [pii]
LID - 10.1016/j.freeradbiomed.2014.10.836 [doi]
AB  - Peroxisome proliferator activated receptor g co-activator 1alpha (PGC-1alpha) is a 
      regulator of oxidative metabolism and reactive oxygen species (ROS) homeostasis 
      that has been show to play a relevant role in angiogenesis. PGC-1alpha KO mice show 
      reduced vascular density in the retinas and KO primary vascular endothelial cells 
      (ECs) migrate faster than the wild type, an effect that can be rescued by 
      antioxidants, suggesting that excessive ROS levels might be relevant in PGC-1 alpha 
      role in angiogenesis. This study aims to investigate the role of ROS homeostasis 
      on the regulation by PGC-1 alpha of angiogenesis. We found that endothelial cells 
      (ECs) from mice deleted for PGC-1 alpha display attenuated adhesion to the 
      extracellular matrix, together with slower spreading, reduced formation of 
      cellular junctions, a disorganized cytoskeleton and random motility, and a 
      enhanced tip phenotype. Aditionally, PGC-1 alpha -deleted ECs exhibit an altered 
      response to vascular endothelial growth factor-A (VEGF-A). In vivo, deletion of 
      PGC-1 alpha results in addition to reduced retinal vascular density, sparse pericyte 
      coverage. Exposure of PGC-1 alpha deleted mice to hyperoxia during retinal vascular 
      development exacerbates these vascular abnormalities and mice show extensive 
      retinal hemorrhaging, with highly unstructured areas and very poor perfusion, 
      compared with wild-type mice. Structural analysis demonstrates a reduction of 
      endothelial VE-cadherin, suggesting defective inter-cellular junctions. 
      Interestingly, this hyperoxia-induced phenotype is partially reversed by 
      antioxidant administration, indicating that elevated production of mitochondrial 
      reactive oxygen species (ROS) in the absence of PGC-1 alpha is functionally 
      important. Finally, in vitro studies show that antioxidant treatment improves 
      VEGF-A signaling, suggesting that toxic effect of ROS may be caused by the 
      alteration of the VEGF-A signaling pathway. In summary, our findings indicate 
      that PGC-1 alpha control of ROS homeostasis plays an important role in the control of 
      de novo angiogenesis, and is required for vascular stability.
CI  - Copyright (c) 2014. Published by Elsevier Inc.
FAU - Garcia-Quintans, Nieves
AU  - Garcia-Quintans N
AD  - Instituto de Investigaciones Biomedicas "Alberto Sols" (CSIC-UAM). Arturo 
      Duperier 4. 28029-Madrid (Spain).
FAU - Sanchez-Ramos, Cristina
AU  - Sanchez-Ramos C
AD  - Instituto de Investigaciones Biomedicas "Alberto Sols" (CSIC-UAM). Arturo 
      Duperier 4. 28029-Madrid (Spain).
FAU - Tierrez, Alberto
AU  - Tierrez A
AD  - Fundacion Centro Nacional de Investigaciones Cardiovasculares Carlos III, Melchor 
      Fernandez Almagro 3, 28029-Madrid (Spain).
FAU - Olmo, Yolanda
AU  - Olmo Y
AD  - Fundacion Centro Nacional de Investigaciones Cardiovasculares Carlos III, Melchor 
      Fernandez Almagro 3, 28029-Madrid (Spain).
FAU - Luque, Alfonso
AU  - Luque A
AD  - Fundacion Centro Nacional de Investigaciones Cardiovasculares Carlos III, Melchor 
      Fernandez Almagro 3, 28029-Madrid (Spain).
FAU - Arza, Elvira
AU  - Arza E
AD  - Fundacion Centro Nacional de Investigaciones Cardiovasculares Carlos III, Melchor 
      Fernandez Almagro 3, 28029-Madrid (Spain).
FAU - Alfranca, Arantzazu
AU  - Alfranca A
AD  - Fundacion Centro Nacional de Investigaciones Cardiovasculares Carlos III, Melchor 
      Fernandez Almagro 3, 28029-Madrid (Spain).
FAU - Miguel Redondo, Juan
AU  - Miguel Redondo J
AD  - Fundacion Centro Nacional de Investigaciones Cardiovasculares Carlos III, Melchor 
      Fernandez Almagro 3, 28029-Madrid (Spain).
FAU - Monsalve, Maria
AU  - Monsalve M
AD  - Instituto de Investigaciones Biomedicas "Alberto Sols" (CSIC-UAM). Arturo 
      Duperier 4. 28029-Madrid (Spain).
LA  - eng
PT  - Journal Article
DEP - 20141210
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
OTO - NOTNLM
OT  - PGC-1 alpha
OT  - ROS
OT  - angiogenesis
OT  - vascular endothelium
EDAT- 2015/10/16 06:00
MHDA- 2015/10/16 06:01
CRDT- 2015/10/14 06:00
PHST- 2015/10/14 06:00 [entrez]
PHST- 2015/10/16 06:00 [pubmed]
PHST- 2015/10/16 06:01 [medline]
AID - S0891-5849(14)01337-9 [pii]
AID - 10.1016/j.freeradbiomed.2014.10.836 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2014 Oct;75 Suppl 1:S5. doi: 
      10.1016/j.freeradbiomed.2014.10.836. Epub 2014 Dec 10.