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Effect of 15-lipoxygenase metabolites on angiogenesis: 15(S)-HPETE is angiostatic and 15(S)-HETE is angiogenic

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Abstract

Objective

15(S)-Hydroxyeicosatetraenoic acid [15(S)-HETE] and 15(S)-hydroperoxyeicosatetraenoic acid [15(S)-HPETE] are the products of arachidonic acid formed in the 15-lipoxygenase pathway. They have opposing effects on the inflammatory process. The present study was designed to examine the role of these metabolites on angiogenesis, which is critically associated with inflammatory conditions.

Methods

Chick chorio-allantoic membrane (CAM), rat aortic rings and human umbilical vein endothelial cells (HUVECs) in culture were used to study the effect of 15(S)-HETE and 15(S)-HPETE on angiogenesis. Biochemical markers of angiogenesis were analysed by ELISA.

Results

15(S)-HETE increased vessel density in chick CAM, induced sprouting in rat aortic rings and increased endothelial cell–cell contact and formation of tubular network-like structures in HUVECs. Furthermore, it up-regulated the expression of CD31, E-selectin and vascular endothelial growth factor (VEGF) in HUVECs, indicating its pro-angiogenic effect. 15(S)-HPETE, on the other hand, decreased vessel density in chick CAM, down-regulated the expression of E-selectin (<35 %), VEGF (<90 %) and CD31 (<50 %) and did not produce sprouting in aortic rings, suggesting an anti-angiogenic property. 15(S)-HETE-mediated up-regulation of CD 31 and VEGF was reversed by treatment with 15(S)-HPETE.

Conclusion

These results indicate the divergent effects of hydroxy and hydroperoxy products of 15-LOX on angiogenesis, highlighting the role of these products in the co-dependence of inflammation and angiogenesis.

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Acknowledgments

Financial assistance to Soumya S. J. and Binu S. in the form of JRF from University Grants Commission (UGC) under Research Fellowship in Sciences for Meritorious Students (RFSMS) scheme, New Delhi and Kerala State Council for Science, Technology and Environment (KSCSTE), Thiruvananthapuram and CSIR PDF to Dr. Anil Kumar K. is gratefully acknowledged. We greatly acknowledge the doctors and nursing staffs of Gowreesha Hospital and Anadiyil Hospital for the help received in obtaining umbilical cord for this study.

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Authors and Affiliations

  1. Department of Biochemistry, University of Kerala, Kariavattom, Thiruvananthapuram, 695 581, Kerala, India

    Sasikumar J. Soumya, Sheela Binu, A. Helen & Perumana R. Sudhakaran

  2. Department of Animal Sciences, School of Life Sciences, University of Hyderabad, Hyderabad, 500 046, India

    K. Anil Kumar & P. Reddanna

  3. Department of Biochemistry and Molecular Biology, School of Biological Sciences, Central University of Kerala, Riverside Transit Campus, Padennakkad, Nileswar, Kasargod, 671 328, Kerala, India

    Perumana R. Sudhakaran

Authors
  1. Sasikumar J. Soumya
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  2. Sheela Binu
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  3. A. Helen
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  4. K. Anil Kumar
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  6. Perumana R. Sudhakaran
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Correspondence to Perumana R. Sudhakaran.

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Responsible Editor: Makoto Katori.

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Soumya, S.J., Binu, S., Helen, A. et al. Effect of 15-lipoxygenase metabolites on angiogenesis: 15(S)-HPETE is angiostatic and 15(S)-HETE is angiogenic. Inflamm. Res. 61, 707–718 (2012). https://doi.org/10.1007/s00011-012-0463-5

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  • DOI: https://doi.org/10.1007/s00011-012-0463-5

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