Statins activate GATA-6 and induce differentiated vascular smooth muscle cells

Journal Article · Fri Oct 03 00:00:00 EDT 2008 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2008.07.098· OSTI ID:21143888

Wada, Hiromichi ^[1]; Abe, Mitsuru; Ono, Koh ^[2]; Morimoto, Tatsuya; Kawamura, Teruhisa; Takaya, Tomohide ^[1]; Satoh, Noriko ^[3]; Fujita, Masatoshi ^[4]; Kita, Toru ^[2]; Shimatsu, Akira ^[5]; Hasegawa, Koji ^[1]

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1. Division of Translational Research, National Hospital Organization Kyoto Medical Center, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto 612-8555 (Japan)
2. Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto (Japan)
3. Division of Metabolic Research, National Hospital Organization Kyoto Medical Center, Kyoto (Japan)
4. Department of Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto (Japan)
5. Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto (Japan)

The beneficial effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) beyond cholesterol lowering involve their direct actions on vascular smooth muscle cells (VSMCs). However, the effects of statins on phenotypic modulation of VSMCs are unknown. We herein show that simvastatin (Sm) and atorvastatin (At) inhibited DNA synthesis in human aortic VSMCs dose-dependently, while cell toxicity was not observed below the concentration of 1 {mu}M of Sm or 100 nM of At. Stimulating proliferative VSMCs with Sm or At induced the expression of SM-{alpha}-actin and SM-MHC, highly specific markers of differentiated phenotype. Sm up-regulated the binding activity of GATA-6 to SM-MHC GATA site and activated the transfected SM-MHC promoter in proliferative VSMCs, while mutating the GATA-6 binding site abolished this activation. Geranylgeranylpyrophosphate (10 {mu}M), an inhibitor of Rho family proteins, abolished the statin-mediated induction of the differentiated phenotype in VSMCs. These findings suggest that statins activate GATA-6 and induce differentiated VSMCs.

• OSTI ID: 21143888
• Journal Information: Biochemical and Biophysical Research Communications, Vol. 374, Issue 4; Other Information: DOI: 10.1016/j.bbrc.2008.07.098; PII: S0006-291X(08)01444-7; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ACTIN
CHOLESTEROL
COENZYMES
DNA
MUSCLES
PHENOTYPE
PROMOTERS
TOXICITY