20-HETE increases survival and decreases apoptosis in pulmonary arteries and pulmonary artery endothelial cells

Anuradha Dhanasekaran, Sreedhar Bodiga, Stephanie Gruenloh, Ying Gao, Laurel Dunn, J R Falck, J. Noelle Buonaccorsi, Meetha Medhora, Elizabeth R. Jacobs

Research output: Contribution to journalArticle

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Abstract

20-Hydroxyeicosatetraenoic acid (20-HETE) is an endogenous cytochrome P-450 product present in vascular smooth muscle and uniquely located in the vascular endo- thelium of pulmonary arteries (PAs). 20-HETE enhances reactive oxygen species (ROS) production of bovine PA endothelial cells (BPAECs) in an NADPH oxidase-dependent manner and is postulated to promote angiogenesis via activation of this pathway in systemic vascular beds. We tested the capacity of 20-HETE or a stable analog of this compound, 20-hydroxy-eicosa-5(Z),14(Z)- dienoic acid, to enhance survival and protect against apoptosis in BPAECs stressed with serum starvation. 20-HETE produced a concentration-dependent increase in numbers of starved BPAECs and increased 5-bromo-2′- deoxyuridine incorporation. Caspase-3 activity, nuclear fragmentation studies, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays supported protection from apoptosis and enhanced survival of starved BPAECs treated with a single application of 20-HETE. Protection from apoptosis depended on intact NADPH oxidase, phosphatidylinositol 3 (PI3)-kinase, and ROS production. 20-HETE-stimulated ROS generation by BPAECs was blocked by inhibition of PI3-kinase or Akt activity. These data suggest 20-HETE- associated protection from apoptosis in BPAECs required activation of PI3-kinase and Akt and generation of ROS. 20-HETE also protected against apoptosis in BPAECs stressed by lipopolysaccharide, and in mouse PAs exposed to hypoxia reoxygenation ex vivo. In summary, 20-HETE may afford a survival advantage to BPAECs through activation of prosurvival PI3-kinase and Akt pathways, NADPH oxidase activation, and NADPH oxidase-derived superoxide.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume296
Issue number3
DOIs
StatePublished - Mar 2009

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Pulmonary Artery
Endothelial Cells
Apoptosis
Phosphatidylinositol 3-Kinase
NADPH Oxidase
Reactive Oxygen Species
20-hydroxy-5,8,11,14-eicosatetraenoic acid
Vascular Endothelium
Bromodeoxyuridine
Starvation
Vascular Smooth Muscle
Superoxides
Caspase 3
Cytochrome P-450 Enzyme System
Blood Vessels
Lipopolysaccharides
Acids
Serum

Keywords

  • Akt
  • Hypoxia
  • Phosphatidylinositol 3-kinase
  • Reactive oxygen species
  • Reduced nicotinamide adenine dinucleotide phosphatase oxidase

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

20-HETE increases survival and decreases apoptosis in pulmonary arteries and pulmonary artery endothelial cells. / Dhanasekaran, Anuradha; Bodiga, Sreedhar; Gruenloh, Stephanie; Gao, Ying; Dunn, Laurel; Falck, J R; Buonaccorsi, J. Noelle; Medhora, Meetha; Jacobs, Elizabeth R.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 296, No. 3, 03.2009.

Research output: Contribution to journalArticle

Dhanasekaran, Anuradha ; Bodiga, Sreedhar ; Gruenloh, Stephanie ; Gao, Ying ; Dunn, Laurel ; Falck, J R ; Buonaccorsi, J. Noelle ; Medhora, Meetha ; Jacobs, Elizabeth R. / 20-HETE increases survival and decreases apoptosis in pulmonary arteries and pulmonary artery endothelial cells. In: American Journal of Physiology - Heart and Circulatory Physiology. 2009 ; Vol. 296, No. 3.
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AU - Dunn, Laurel

AU - Falck, J R

AU - Buonaccorsi, J. Noelle

AU - Medhora, Meetha

AU - Jacobs, Elizabeth R.

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