title: Increased migration of monocytes in essential hypertension is associated with increased transient receptor potential channel canonical type 3 channels.
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.
authors.affiliation: Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhao
authors.forename: Yinxing
authors.initials: Y
authors.lastname: Ni
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Jian
authors.initials: J
authors.lastname: Zhong
authors.forename: Hao
authors.initials: H
authors.lastname: Yu
authors.forename: Xingsen
authors.initials: X
authors.lastname: Xu
authors.forename: Hongbo
authors.initials: H
authors.lastname: He
authors.forename: Zhencheng
authors.initials: Z
authors.lastname: Yan
authors.forename: Alexandra
authors.initials: A
authors.lastname: Scholze
authors.forename: Daoyan
authors.initials: D
authors.lastname: Liu
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Zhu
authors.forename: Martin
authors.initials: M
authors.lastname: Tepel
mesh_terms: D000368:Aged; D001483:Base Sequence; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000097:blood; D016022:Case-Control Studies; D002465:Cell Movement; D003600:Cytosol / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D006973:Hypertension / Q000097:blood*; D066298:In Vitro Techniques; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000097:blood; D011505:Protein-Tyrosine Kinases / Q000097:blood; D051057:Proto-Oncogene Proteins c-akt / Q000097:blood; D034741:RNA, Small Interfering / Q000235:genetics; D050052:TRPC Cation Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000097:blood* / Q000235:genetics
chemical_list: D001896:Boron Compounds; D034741:RNA, Small Interfering; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D009240:N-Formylmethionine Leucyl-Phenylalanine; C109986:2-aminoethoxydiphenyl borate; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt; D002118:Calcium