TRPV1 activation plays a critical role in 14,15-EET-increased angiogenesis. (A) HMECs were cultured in pre-coated Matrigel and pretreated with 10 μM CPZ or 10 μM SB366791 for 2 h, then incubated with 10 nM 14,15-EET for 12 h. Bar graphs indicate the total number of tube branch points in 5 randomly selected microscopy views. Data are mean ± SEM from 5 independent experiments. *, P<0.05 versus vehicle; #, P<0.05 versus 14,15-EET. (B) Eight week-old mice were subcutaneously injected with Matrigel plugs containing 50 U/ml heparin with or without 14,15-EET (10 nM) or CPZ (10 μM) and TRPV1-/- mice were subcutaneously injected with Matrigel with or without 14,15-EET (10 nM). After 7 days, Matrigel plugs were isolated and photographed. The haemoglobin content of the plugs was measured to indicate functional angiogenesis. Data are mean ± SEM from 9 mice. *, P<0.05 versus WT mice without 14,15-EET; #, P<0.05 versus WT mice with 14,15-EET. (C) The proposed molecular mechanism of TRPV1 activation by 14,15-EET for endothelial NO production and angiogenesis. TRPV1 is involved in 14,15-EET-mediated increase of intracellular Ca2+, NO production and induction of endothelial angiogenesis.