Int J Biol Sci 2014; 10(9):990-996. doi:10.7150/ijbs.9832

Short Research Communication

Implication of Transient Receptor Potential Vanilloid Type 1 in 14,15-Epoxyeicosatrienoic Acid-induced Angiogenesis

Kuo-Hui Su1,*, Kuan-I Lee1,*, Song-Kun Shyue2, Hsiang-Ying Chen1, Jeng Wei3,✉, Tzong-Shyuan Lee 1,✉

1. Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, 11221 Taiwan;
2. Institute of Biomedical Sciences, Academia Sinica, Taipei, 11529 Taiwan;
3. Heart Center, Cheng-Hsin General Hospital, Taipei, 11221 Taiwan.
*These authors equally contributed to this work.


14,15-epoxyeicosatrienoic acid (14,15-EET) is implicated in regulating physiological functions of endothelial cells (ECs), yet the potential molecular mechanisms underlying the beneficial effects in ECs are not fully understood. In this study, we investigated whether transient receptor potential vanilloid receptor type 1 (TRPV1) is involved in 14,15-EET-mediated Ca2+ influx, nitric oxide (NO) production and angiogenesis. In human microvascular endothelial cells (HMECs), 14,15-EET time-dependently increased the intracellular level of Ca2+. Removal of extracellular Ca2+, pharmacological inhibition or genetic disruption of TRPV1 abrogated 14,15-EET-mediated increase of intracellular Ca2+ level in HMECs or TRPV1-transfected HEK293 cells. Furthermore, removal of extracellular Ca2+ or pharmacological inhibition of TRPV1 decreased 14,15-EET-induced NO production. 14,15-EET-mediated tube formation was abolished by TRPV1 pharmacological inhibition. In an animal experiment, 14,15-EET-induced angiogenesis was diminished by inhibition of TRPV1 and in TRPV1-deficient mice. TRPV1 may play a crucial role in 14,15-EET-induced Ca2+ influx, NO production and angiogenesis.

Keywords: transient receptor potential vanilloid 1, epoxyeicosatrienoic acid, angiogenesis, calcium, endothelial cell.

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How to cite this article:
Su KH, Lee KI, Shyue SK, Chen HY, Wei J, Lee TS. Implication of Transient Receptor Potential Vanilloid Type 1 in 14,15-Epoxyeicosatrienoic Acid-induced Angiogenesis. Int J Biol Sci 2014; 10(9):990-996. doi:10.7150/ijbs.9832. Available from