| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1From the Departments of Physiology and 4Ophthalmology, University of Tennessee Health Science Center, Memphis, Tennessee; 2Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, Georgia; and 3Vanderbilt Eye Institute, Vanderbilt University School of Medicine, Nashville, Tennessee.
PURPOSE. To examine for the expression of 15-lipoxygenase 1 (15-LOX1) and 15-LOX2 in human retinal microvascular endothelial cells (HRMVECs) and study the role of arachidonic acid metabolites of these enzymes in angiogenesis.
METHODS. Quantitative RT-PCR and reverse-phase HPLC analyses were used to determine 15-LOX1/2 expression and their arachidonic acid metabolites in HRMVECs. The role of MEK1 in 15(S)-HETE–induced angiogenesis was studied using HRMVEC migration, tube formation, and basement membrane matrix plug angiogenesis.
RESULTS. HRMVECs expressed both 15-LOX1 and 15-LOX2. Hypoxia induced the expression of 15-LOX1 and the production of its arachidonic acid metabolites 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE) and 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE). 15(S)-HETE stimulated HRMVEC migration and tube formation as potently as 20 ng/mL fibroblast growth factor-2 (FGF-2). In addition, 15(S)-HETE stimulated the phosphorylation of ERK1/2, JNK1, p38 MAPK, and MEK1 in a time-dependent manner in these cells. Inhibition of MEK1 by pharmacologic and dominant-negative mutant approaches attenuated 15(S)-HETE–induced phosphorylation of ERK1/2 and JNK1 but not p38 MAPK. Blockade of ERK1/2 and JNK1 activation suppressed 15(S)-HETE–induced HRMVEC migration and tube formation and basement membrane matrix plug angiogenesis. Inhibition of p38 MAPK attenuated 15(S)-HETE–induced HRMVEC migration only. Inhibition of MEK1 also blocked 15(S)-HETE–induced HRMVEC migration and tube formation and basement membrane matrix plug angiogenesis.
CONCLUSIONS. These results suggest that hypoxia, through the induction of 15-LOX1 expression, leads to the production of 15(S)-HETE in HRMVECs. In addition, 15(S)-HETE, through MEK1-dependent activation of ERK1/2 and JNK1, stimulates the angiogenic differentiation of HRMVECs and basement membrane matrix plug angiogenesis.
This article has been cited by other articles:
|
|
 |
|
  S. Y. Cheranov, D. Wang, V. Kundumani-Sridharan, M. Karpurapu, Q. Zhang, K. R. Chava, and G. N. Rao The 15(S)-hydroxyeicosatetraenoic acid-induced angiogenesis requires Janus kinase 2-signal transducer and activator of transcription-5B-dependent expression of interleukin-8 Blood, June 4, 2009; 113(23): 6023 - 6033. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. R. Chava, M. Karpurapu, D. Wang, M. Bhanoori, V. Kundumani-Sridharan, Q. Zhang, T. Ichiki, W. C. Glasgow, and G. N. Rao CREB-Mediated IL-6 Expression Is Required for 15(S)-Hydroxyeicosatetraenoic Acid-Induced Vascular Smooth Muscle Cell Migration Arterioscler. Thromb. Vasc. Biol., June 1, 2009; 29(6): 809 - 815. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Zhao, D. Wang, S. Y. Cheranov, M. Karpurapu, K. R. Chava, V. Kundumani-Sridharan, D. A. Johnson, J. S. Penn, and G. N. Rao A novel role for activating transcription factor-2 in 15(S)-hydroxyeicosatetraenoic acid-induced angiogenesis J. Lipid Res., March 1, 2009; 50(3): 521 - 533. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. T. Aggarwal, S. L. Pfister, K. M. Gauthier, Y. Chawengsub, J. E. Baker, and W. B. Campbell Chronic hypoxia enhances 15-lipoxygenase-mediated vasorelaxation in rabbit arteries Am J Physiol Heart Circ Physiol, March 1, 2009; 296(3): H678 - H688. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
