HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 291/2/H517    most recent 00953.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (13) Citing Articles via Google Scholar Google Scholar Articles by Dhanasekaran, A. Articles by Medhora, M. Search for Related Content PubMed PubMed Citation Articles by Dhanasekaran, A. Articles by Medhora, M.

CALL FOR PAPERS
Regulation of Cardiovascular Functions by Eicosanoids and other Lipid Mediators

Protective effects of epoxyeicosatrienoic acids on human endothelial cells from the pulmonary and coronary vasculature

¹Division of Pulmonary and Critical Care, Department of Medicine; ²Department of Physiology; ³Division of Cardiology, Department of Medicine and Zablocki Veterans Affairs Medical Center; and ⁴Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin

Submitted 6 September 2005 ; accepted in final form 3 March 2006

Epoxyeicosatrienoic acids (EETs) are cytochrome P-450 (CYP) metabolites synthesized from the essential fatty acid arachidonic acid to generate four regioisomers, 14,15-, 11,12-, 8,9-, and 5,6-EET. Cultured human coronary artery endothelial cells (HCAECs) contain endogenous EETs that are increased by stimulation with physiological agonists such as bradykinin. Because EETs are known to modulate a number of vascular functions, including angiogenesis, we tested each of the four regioisomers to characterize their effects on survival and apoptosis of HCAECs and cultured human lung microvascular endothelial cells (HLMVECs). A single application of physiologically relevant concentration of 14,15-, 11,12-, and 8,9-EET but not 5,6-EET (0.75–300 nM) promoted concentration-dependent increase in cell survival of HLMVECs and HCAECs after removal of serum. The lipids also protected the same cells from death via the intrinsic, as well as extrinsic, pathways of apoptosis. EETs did not increase intracellular calcium concentration ([Ca²⁺]_i) or phosphorylate mitogen-activated protein kinase p44/42 when applied to these cells, and their protective action was attenuated by the phosphotidylinositol-3 kinase inhibitor wortmannin (10 µM) but not the cyclooxygenase inhibitor indomethacin (20 µM). Our results demonstrate for the first time the capacity of EETs to enhance human endothelial cell survival by inhibiting both the intrinsic, as well as extrinsic, pathways of apoptosis, an important underlying mechanism that may promote angiogenesis and endothelial survival during atherosclerosis and related cardiovascular ailments.

cytochrome P-450; eicosanoids; epoxygenase; apoptosis; calcium signaling

This article has been cited by other articles:

				A. Dhanasekaran, S. Bodiga, S. Gruenloh, Y. Gao, L. Dunn, J. R. Falck, J. N. Buonaccorsi, M. Medhora, and E. R. Jacobs 20-HETE increases survival and decreases apoptosis in pulmonary arteries and pulmonary artery endothelial cells Am J Physiol Heart Circ Physiol, March 1, 2009; 296(3): H777 - H786. [Abstract] [Full Text] [PDF]

				G. J. Gross, K. M. Gauthier, J. Moore, J. R. Falck, B. D. Hammock, W. B. Campbell, and K. Nithipatikom Effects of the selective EET antagonist, 14,15-EEZE, on cardioprotection produced by exogenous or endogenous EETs in the canine heart Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2838 - H2844. [Abstract] [Full Text] [PDF]

				M. Medhora, Y. Chen, S. Gruenloh, D. Harland, S. Bodiga, J. Zielonka, D. Gebremedhin, Y. Gao, J. R. Falck, S. Anjaiah, et al. 20-HETE increases superoxide production and activates NAPDH oxidase in pulmonary artery endothelial cells Am J Physiol Lung Cell Mol Physiol, May 1, 2008; 294(5): L902 - L911. [Abstract] [Full Text] [PDF]

				A. Dhanasekaran, S. K. Gruenloh, J. N. Buonaccorsi, R. Zhang, G. J. Gross, J. R. Falck, P. K. Patel, E. R. Jacobs, and M. Medhora Multiple antiapoptotic targets of the PI3K/Akt survival pathway are activated by epoxyeicosatrienoic acids to protect cardiomyocytes from hypoxia/anoxia Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H724 - H735. [Abstract] [Full Text] [PDF]

				S. Yang, L. Lin, J.-X. Chen, C. R. Lee, J. M. Seubert, Y. Wang, H. Wang, Z.-R. Chao, D.-D. Tao, J.-P. Gong, et al. Cytochrome P-450 epoxygenases protect endothelial cells from apoptosis induced by tumor necrosis factor-{alpha} via MAPK and PI3K/Akt signaling pathways Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H142 - H151. [Abstract] [Full Text] [PDF]