title: Pitavastatin Regulates Ang II Induced Proliferation and Migration via IGFBP-5 in VSMC.
abstract: Angiotensin II (Ang II), a key mediator of hypertensive, causes structural changes in the arteries (vascular remodeling), which involve alterations in cell growth, vascular smooth muscle cell (VSMC) hypertrophy. Ang II promotes fibrotic factor like IGFBP5, which mediates the profibrotic effects of Ang II in the heart and kidneys, lung and so on. The purpose of this study was to identify the signaling pathway of IGFBP5 on cell proliferation and migration of Ang II-stimulated VSMC. We have been interested in Ang II-induced IGFBP5 and were curious to determine whether a Pitavastatin would ameliorate the effects. Herein, we investigated the question of whether Ang II induced the levels of IGFBP5 protein followed by proliferation and migration in VSMC. Pretreatment with the specific Angiotensin receptor type 1 (AT1) inhibitor (Losartan), Angiotensin receptor type 2 (AT2) inhibitor (PD123319), MAPK inhibitor (U0126), ERK1/2 inhibitor (PD98059), P38 inhibitor (SB600125) and PI3K inhibitor (LY294002) resulted in significantly inhibited IGFBP5 production, proliferation, and migration in Ang II-stimulated VSMC. In addition, IGFBP5 knockdown resulted in modulation of Ang II induced proliferation and migration via IGFBP5 induction. In addition, Pitavastatin modulated Ang II induced proliferation and migration in VSMC. Taken together, our results indicated that Ang II induces IGFBP5 through AT1, ERK1/2, P38, and PI3K signaling pathways, which were inhibited by Pitavastatin. These findings may suggest that Pitavastatin has an effect on vascular disease including hypertension.
authors.affiliation: Department of Pharmacology, College of Medicine, Yeungnam University, Daegu 42415, Korea.
authors.forename: Yu Mi
authors.initials: YM
authors.lastname: Ha
authors.affiliation: School of Food Science & Biotechnology, Kyungpook National University, Daegu 41566, Korea.
authors.forename: Ju-Ock
authors.initials: JO
authors.lastname: Nam
authors.affiliation: Department of Pharmacology, College of Medicine, Yeungnam University, Daegu 42415, Korea.
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Kang
keywords: Hypertension; IGFBP-5; Pitavastatin; Proliferation; VSMC