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

Much of biology, and all of science really, is a game of cause and effect. By observing effects, researchers are drawn to determining causes. From causes, effects can be better understood and perhaps manipulated if it is beneficial to do so. This is the case in the study conducted by Su et al. from National Yang-Ming University in Tapei. They took a closer look at some of the underlying functioning of Epoxyeicosatrienoic acids (EETs), specifically 14,15-EET. The justification for this was largely that much is known about what EETs do, but little is known about their underlying molecular mechanisms. For example, EETs play an important role in vascular function by regulating the membrane hyperpolarization of smooth muscle cells through the activation of calcium (Ca2⁺)-activated channels. Additionally, EETs have been found to have beneficial effects on pathophysiological functions of endothelial cells (ECs) and have also been found to induce the expression of vascular endothelial growth. Yet another function of EETs is in promoting angiogenesis in ECs. In general, much is known about EETs involvement in vascular function, but little is known about what goes on at a molecular level to give EETs this role.

Transient receptor potential vanilloid type 1 (TRPV1) is a crucial substance for understanding interactions among neurons and recent evidence has suggested that they could have a similar effect in ECs and other vascular functions. Because of this, this study sets out to the determine the role of TRPV1 in 14,15-EET-promoted angiogenesis in ECs and mice. The study concludes that the administration of 14,15-EET may trigger TRPV1-dependent Ca²⁺ influx and NO production, which leads to increased EC tube formation and angiogenesis. To understand the role that TRPV1 plays in this calcium influx, the researchers used the Fluo-8 AM fluorescent indicator to track calcium flows. This is such a critical tool because it produces much brighter signals. Without this, the possibility exists for discrepancies in readings, which can call into question the validity of results.

The findings of this study are important because they help to shed further light on the molecular interactions dealing with vascular function. By showing that TRPV1 is engaged in 14,15-EET-elicited angiogenesis, the possibility now exists to consider the therapeutic value of EETs in treating eNOS-related (endothelial nitric oxide synthase) cardiovascular diseases. The results from this study go a long way in providing the causes for some observed effects, which create a better understanding of the mechanisms at work and allow for manipulation and therapy. Without reliable, easy-to-use indicators like Fluo-8 AM, readings of this magnitude would not be possible. Since the indicator can be loaded easily and is not temperature dependent, it interferes minimally with the sample and maintains the integrity of the results. Every day researchers are gaining a more thorough understanding of the workings of the human body, and this is due in large part to the advanced, accurate and reliable tools they have available to them to use in groundbreaking research.

References

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1. Su, Kuo-Hui, et al. "Implication of transient receptor potential vanilloid type 1 in 14, 15-epoxyeicosatrienoic acid-induced angiogenesis." International journal of biological sciences 10.9 (2014): 990.