Abstract
Increased transient receptor potential canonical type 3 (TRPC3) channels have been observed in patients with essential hypertension. In the present study we tested the hypothesis that increased monocyte migration is associated with increased TRPC3 expression. Monocyte migration assay was performed in a microchemotaxis chamber using chemoattractants formylated peptide Met-Leu-Phe (fMLP) and tumor necrosis factor-α (TNF-α). Proteins were identified by immunoblotting and quantitative in-cell Western assay. The effects of TRP channel-inhibitor 2–aminoethoxydiphenylborane (2-APB) and small interfering RNA knockdown of TRPC3 were investigated. We observed an increased fMLP-induced migration of monocytes from hypertensive patients compared with normotensive control subjects (246±14% vs 151±10%). The TNF-α-induced migration of monocytes in patients with essential hypertension was also significantly increased compared to normotensive control subjects (221±20% vs 138±18%). In the presence of 2-APB or after siRNA knockdown of TRPC3 the fMLP-induced monocyte migration was significantly blocked. The fMLP-induced changes of cytosolic calcium were significantly increased in monocytes from hypertensive patients compared to normotensive control subjects. The fMLP-induced monocyte migration was significantly reduced in the presence of inhibitors of tyrosine kinase and phosphoinositide 3-kinase. We conclude that increased monocyte migration in patients with essential hypertension is associated with increased TRPC3 channels.
Highlights
An increased transient receptor potential canonical type 3 (TRPC3) protein expression has been observed both in patients with essential hypertension and in animal models of hypertension [1,2,3,4,5]
First we evaluated the migration of monocytes using the chemoattractants formylated peptide Met-Leu-Phe (fMLP) and tumor necrosis factor-a (TNF-a)
In the presence of 2-APB the TNF-a-induced migration of monocytes was significantly reduced to 92610% in normotensive control subjects, and in patients with essential hypertension was significantly reduced to 105612%, each n = 10, p,0.05 compared to their control conditions, Figures 1C
Summary
An increased transient receptor potential canonical type 3 (TRPC3) protein expression has been observed both in patients with essential hypertension and in animal models of hypertension [1,2,3,4,5]. In patients with hypertension an increased TRPC3 expression has been reported in several tissues including vascular smooth muscle cells and peripheral blood monocytes [1,2,5]. Monocytes from patients with essential hypertension show elevated secretion patterns of pro-inflammatory cytokines, an increased expression of adhesion molecules, and an increased adhesion to vascular endothelial cells [9]. Increased activation of monocytes in hypertension may be due to increased change of cytosolic calcium. TRPC3 channels are likely candidates to produce increased activation of monocytes. An increased calcium influx through TRPC3 channels may cause increased migration of monocytes. In the present study we tested the hypothesis that increased TRPC3 channel expression causes increased migration of monocytes from patients with essential hypertension
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