PMID- 27856430
OWN - NLM
STAT- MEDLINE
DCOM- 20170606
LR  - 20200930
IS  - 1522-1563 (Electronic)
IS  - 0363-6143 (Print)
IS  - 0363-6143 (Linking)
VI  - 312
IP  - 1
DP  - 2017 Jan 1
TI  - Glycolysis and oxidative phosphorylation are essential for purinergic 
      receptor-mediated angiogenic responses in vasa vasorum endothelial cells.
PG  - C56-C70
LID - 10.1152/ajpcell.00250.2016 [doi]
AB  - Angiogenesis is an energy-demanding process; however, the role of cellular energy 
      pathways and their regulation by extracellular stimuli, especially extracellular 
      nucleotides, remain largely unexplored. Using metabolic inhibitors of glycolysis 
      (2-deoxyglucose) and oxidative phosphorylation (OXPHOS) (oligomycin, rotenone, 
      and FCCP), we demonstrate that glycolysis and OXPHOS are both essential for 
      angiogenic responses of vasa vasorum endothelial cell (VVEC). Treatment with P2R 
      agonists, ATP, and 2-methylthioadenosine diphosphate trisodium salt (MeSADP), but 
      not P1 receptor agonist, adenosine, increased glycolytic activity in VVEC 
      (measured by extracellular acidification rate and lactate production). 
      Stimulation of glycolysis was accompanied by increased levels of 
      phospho-phosphofructokinase B3, hexokinase (HK), and GLUT-1, but not lactate 
      dehydrogenase. Moreover, extracellular ATP and MeSADP, and to a lesser extent 
      adenosine, increased basal and maximal oxygen consumption rates in VVEC. These 
      effects were potentiated when the cells were cultured in 20 mM galactose and 5 mM 
      glucose compared with 25 mM glucose. Treatment with P2R agonists decreased 
      phosphorylation of pyruvate dehydrogenase (PDH)-E1alpha and increased succinate 
      dehydrogenase (SDH), cytochrome oxidase IV, and beta-subunit of F(1)F(0) ATP 
      synthase expression. In addition, P2R stimulation transiently elevated 
      mitochondrial Ca(2+) concentration, implying involvement of mitochondria in VVEC 
      angiogenic activation. We also demonstrated a critical role of 
      phosphatidylinositol 3-kinase and Akt pathways in lactate production, PDH-E1alpha 
      phosphorylation, and the expression of HK, SDH, and GLUT-1 in ATP-stimulated 
      VVEC. Together, our findings suggest that purinergic and metabolic regulation of 
      VVEC energy pathways is essential for VV angiogenesis and may contribute to 
      pathologic vascular remodeling in pulmonary hypertension.
CI  - Copyright (c) 2017 the American Physiological Society.
FAU - Lapel, Martin
AU  - Lapel M
AD  - Department of Pediatrics, University of Colorado Denver, Aurora, Colorado.
FAU - Weston, Philip
AU  - Weston P
AD  - Department of Pediatrics, University of Colorado Denver, Aurora, Colorado.
FAU - Strassheim, Derek
AU  - Strassheim D
AD  - Department of Pediatrics, University of Colorado Denver, Aurora, Colorado.
FAU - Karoor, Vijaya
AU  - Karoor V
AD  - Department of Medicine, University of Colorado Denver, Aurora, Colorado; and.
FAU - Burns, Nana
AU  - Burns N
AD  - Department of Pediatrics, University of Colorado Denver, Aurora, Colorado.
FAU - Lyubchenko, Taras
AU  - Lyubchenko T
AD  - Department of Medicine, University of Colorado Denver, Aurora, Colorado; and.
FAU - Paucek, Petr
AU  - Paucek P
AD  - Department of Pharmacology, University of Colorado Denver, Aurora, Colorado.
FAU - Stenmark, Kurt R
AU  - Stenmark KR
AD  - Department of Pediatrics, University of Colorado Denver, Aurora, Colorado.
FAU - Gerasimovskaya, Evgenia V
AU  - Gerasimovskaya EV
AD  - Department of Pediatrics, University of Colorado Denver, Aurora, Colorado; 
      evgenia.gerasimovskaya@ucdenver.edu.
LA  - eng
GR  - P01 HL014985/HL/NHLBI NIH HHS/United States
GR  - R01 HL086783/HL/NHLBI NIH HHS/United States
GR  - R01 HL114887/HL/NHLBI NIH HHS/United States
PT  - Journal Article
DEP - 20161116
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (Receptors, Purinergic)
SB  - IM
MH  - Animals
MH  - Cattle
MH  - Cells, Cultured
MH  - Endothelial Cells/cytology/*physiology
MH  - Glycolysis/*physiology
MH  - Male
MH  - Neovascularization, Physiologic/*physiology
MH  - *Oxidative Phosphorylation
MH  - Receptors, Purinergic
MH  - Vasa Vasorum/*cytology/*physiology
PMC - PMC5283894
OTO - NOTNLM
OT  - OXPHOS
OT  - angiogenesis
OT  - cellular metabolism
OT  - endothelial cells
OT  - glycolysis
OT  - purinergic receptors
OT  - vasa vasorum
EDAT- 2016/11/20 06:00
MHDA- 2017/06/07 06:00
PMCR- 2016/11/16
CRDT- 2016/11/19 06:00
PHST- 2016/08/25 00:00 [received]
PHST- 2016/11/03 00:00 [accepted]
PHST- 2016/11/20 06:00 [pubmed]
PHST- 2017/06/07 06:00 [medline]
PHST- 2016/11/19 06:00 [entrez]
PHST- 2016/11/16 00:00 [pmc-release]
AID - ajpcell.00250.2016 [pii]
AID - C-00250-2016 [pii]
AID - 10.1152/ajpcell.00250.2016 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2017 Jan 1;312(1):C56-C70. doi: 
      10.1152/ajpcell.00250.2016. Epub 2016 Nov 16.