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

36 Scopus citations

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)
Pages (from-to)H777-H786
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume296
Issue number3
DOIs
StatePublished - Mar 1 2009

Keywords

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

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of '20-HETE increases survival and decreases apoptosis in pulmonary arteries and pulmonary artery endothelial cells'. Together they form a unique fingerprint.

  • Cite this