title: Akt1 isoform modulates phenotypic conversion of vascular smooth muscle cells.
abstract: In this study, we investigated the role of Akt1 isoform in phenotypic change of vascular smooth muscle cells (VSMCs) and neointima formation. Laminin-induced conversion of synthetic VSMCs into contractile VSMCs was measured by expression of marker proteins for contractile VSMCs and collagen gel contraction assay. Culture of synthetic VSMCs on laminin-coated plates induced expression of marker proteins for contractile VSMCs and showed contraction in response to angiotensin II (AngII) stimulation. Silencing integrin-linked kinase attenuated activation of Akt and blocked phenotypic conversion of VSMCs resulting in the loss of AngII-dependent contraction. Laminin-induced phenotypic conversion of VSMCs was abrogated by phosphatidylinositol 3-kinase inhibitor or in cells silencing Akt1 but not Akt2. Proliferation of contractile VSMCs on laminin-coated plate was enhanced in cells silencing Akt1 whereas silencing Akt2 did not affect. Promoter activity of myocardin and SM22α was enhanced in contractile phenotype and overexpression of myocardin stimulated promoter activity of SM22α in synthetic phenotype. Promoter activity of myocardin and SM22α was reduced in cells silencing Akt1 and promoter activity of SM22α was restored by overexpression of myocardin in cells silencing Akt1. However, silencing of Akt2 affected neither promoter activity of myocardin nor SM22α. Finally, neointima formation in carotid artery ligation and high fat-diet-induced atherosclerosis was facilitated in mice lacking Akt1. This study demonstrates that Akt1 isoform stimulates laminin-induced phenotypic conversion of synthetic VSMCs by regulating the expression of myocardin. VSMCs become susceptible to shifting from contractile to synthetic phenotype by the loss of Akt1 in pathological conditions.
authors.affiliation: MRC for Ischemic Tissue Regeneration, Department of Pharmacology, Pusan National University School of Medicine, Yangsan, Republic of Korea; Department of Pharmacology, Pusan National University School of Medicine, Yangsan, Republic of Korea.
authors.forename: Sung Ji
authors.initials: SJ
authors.lastname: Yun
authors.affiliation: MRC for Ischemic Tissue Regeneration, Department of Pharmacology, Pusan National University School of Medicine, Yangsan, Republic of Korea; Department of Pharmacology, Pusan National University School of Medicine, Yangsan, Republic of Korea.
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Ha
authors.affiliation: MRC for Ischemic Tissue Regeneration, Department of Pharmacology, Pusan National University School of Medicine, Yangsan, Republic of Korea; Department of Pharmacology, Pusan National University School of Medicine, Yangsan, Republic of Korea.
authors.forename: Eun Kyoung
authors.initials: EK
authors.lastname: Kim
authors.affiliation: MRC for Ischemic Tissue Regeneration, Department of Pharmacology, Pusan National University School of Medicine, Yangsan, Republic of Korea; Department of Pharmacology, Pusan National University School of Medicine, Yangsan, Republic of Korea.
authors.forename: Young Whan
authors.initials: YW
authors.lastname: Kim
authors.affiliation: MRC for Ischemic Tissue Regeneration, Department of Pharmacology, Pusan National University School of Medicine, Yangsan, Republic of Korea; Department of Pharmacology, Pusan National University School of Medicine, Yangsan, Republic of Korea.
authors.forename: Seo Yeon
authors.initials: SY
authors.lastname: Jin
authors.affiliation: Department of Obstetrics and Gynecology, Pusan National University School of Medicine, Yangsan, Republic of Korea.
authors.forename: Dong Hyung
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Pusan National University Hospital, Pusan National University School of Medicine, Yangsan, Republic of Korea.
authors.forename: Sang Heon
authors.initials: SH
authors.lastname: Song
authors.affiliation: MRC for Ischemic Tissue Regeneration, Department of Pharmacology, Pusan National University School of Medicine, Yangsan, Republic of Korea; Department of Pharmacology, Pusan National University School of Medicine, Yangsan, Republic of Korea.
authors.forename: Chi Dae
authors.initials: CD
authors.lastname: Kim
authors.affiliation: Department of Anatomy, Pusan National University School of Korean Medicine, Yangsan, Republic of Korea.
authors.forename: Hwa Kyoung
authors.initials: HK
authors.lastname: Shin
authors.affiliation: MRC for Ischemic Tissue Regeneration, Department of Pharmacology, Pusan National University School of Medicine, Yangsan, Republic of Korea. Electronic address: sunsik@pusan.ac.kr.
authors.forename: Sun Sik
authors.initials: SS
authors.lastname: Bae
keywords: Akt; Integrin-linked kinase; Laminin; Neointima; Phenotypic change