title: Involvement of transient receptor potential canonical 1 (TRPC1) in angiotensin II-induced vascular smooth muscle cell hypertrophy.
abstract: Angiotensin II (Ang II) induces vascular smooth muscle cell (VSMC) hypertrophy as one of the major events leading to atherosclerosis. Increased Ca(2+) entry is an important stimulus for VSMC hypertrophy, but the association with Ang II remains to be determined. Transient receptor potential canonical 1 (TRPC1) forms store-operated Ca(2+) (SOC) channels that are involved in Ca(2+) homeostasis. Our aim was to ascertain the potential involvement of TRPC1 in Ang II-induced VSMC hypertrophy. For this purpose, we used cultured human coronary artery smooth muscle cells (hCASMCs). Store-operated Ca(2+) entry (SOCE) increased in the Ang II-induced hypertrophied cells, and SOC channel blocker inhibited the Ang II-induced hypertrophic response. Although hCASMCs constitutively expressed TRPC1, C3, C4, C5, and C6, only TRPC1 increased in response to Ang II stimulation. TRPC1 siRNA decreased SOCE and prevented Ang II-induced hypertrophy. We found NF-kappaB binding sites in the 5'-regulatory region of the human TRPC1 gene. An electrophoretic mobility shift assay showed that Ang II increased the TRPC1 promoter's NF-kappaB binding activity. Co-treatment with NF-kappaB decoy oligonucleotides not only reduced TRPC1 expression, but also inhibited the hypertrophic responses. In conclusion, our data suggest that Ang II and subsequent NF-kappaB activation induces hCASMC hypertrophy through an enhancement of TRPC1 expression.
authors.affiliation: Second Department of Internal Medicine, Akita University School of Medicine, 1-1-1 Hondoh, Akita 010-8543, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Watanabe
authors.forename: Manabu
authors.initials: M
authors.lastname: Murakami
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Ohba
authors.forename: Milena
authors.initials: M
authors.lastname: Radovanovic
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Ono
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Iijima
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ito
mesh_terms: D000804:Angiotensin II / Q000502:physiology; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology / Q000503:physiopathology; D006801:Humans; D006984:Hypertrophy / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000503:physiopathology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D016328:NF-kappa B / Q000502:physiology; D050052:TRPC Cation Channels / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D050052:TRPC Cation Channels; C096351:transient receptor potential cation channel, subfamily C, member 1; D000804:Angiotensin II