Erythropoietin and TRPV1 together in new formation.

Abstract

Today's lifestyle with excess food and little exercise increases the number of people with metabolic syndrome and cardiovascular disease. New knowledge of treatments in this field is central. Recent years have drawn attention to erythropoietin (EPO) and control of hypertension through effects on endothelial cells. EPO is more known for its important role as a cytokine in the formation of new red blood cells, but during latter years, EPO has been demonstrated to exert other non-haematopoietic functions. These include tissue production, reduced apoptosis, anti-inflammatory effects and angiogenesis (Lombardero et al. 2011). In the current issue of Acta Physiologica, Yu et al. demonstrate EPO-induced calcium influx in the endothelial cells via activation of the vanilloid receptor subtype 1 (TRPV1) channel (Yu et al. 2016). TRPV1 is a non-selective calcium influx channel regulated by capsaicin, the piquancy in hot chilli pepper, but this is not the only stimulus of this channel. The TRPV1 channel has also been shown to be thermosensitive and osmosensitive, to be regulated by mechanical stimuli (Baylie & Brayden 2011) and to be activated by heat, low pH and lipids. TRPV1 was discovered in 1997 by David Julius and colleagues which resulted in a major breakthrough in the field of somatic sensory biology, where they have been mostly described and have important roles. The channel has since its discovery been an important target for pain relief (Szallasi et al. 2007). TRPV1 is also one of the major calcium influx channels in endothelial cells, and TRPV1 modulators have been suggested also in the treatment of kidney failure (Kassmann et al. 2013). One of the most conclusive experiments demonstrating TRPV1 channel involvement in vascular endothelial cells was performed in mouse aortic endothelial cells. In that preparation, capsaicin increased intracellular calcium and the phosphorylation of eNOS and activated PKA. In the same study, it was for first time shown that capsaicin could lower blood pressure of hypertensive rats (Yang et al. 2010). Production of NO in endothelial cells is a key in the maintenance of their function and occurs through the activity of eNOS. The mission to maintain high levels of NO has been suggested as pharmacological treatment of cardiovascular disease, and pharmacological activation of TRPV1 channels prevents hypertension (Yang et al. 2010, Kassmann et al. 2013). The novelty in the current work is the link between EPO and TRPV1 channels (Yu et al. 2016). Separately, EPO and TRPV1 have been shown to increase NO production. Here, Yu et al. show with the use of TRPV1−/− animals and HEK293 transfected cells that EPO can activate TRPV1 channels through a phospholipase PLC-γ1 pathway. Moreover, the authors confirm that the activation of TRPV1 by EPO and via PLC-γ1 acts through the Akt-AMPK-eNOS-NO cascade. Finally, they demonstrate EPO-activated NO production via TRPV1 is important for angiogenesis. The results are promising, and the future will shed new light into how these interesting findings can be utilized in therapeutic treatment of cardiovascular disease. There are no conflict of interest.