Original Article

Hypertension Research (2011) 34, 949–956; doi:10.1038/hr.2011.64; published online 16 June 2011

Angiotensin II induces microtubule reorganization mediated by a deacetylase SIRT2 in endothelial cells

Aiko Hashimoto-Komatsu1, Tetsuaki Hirase1,2, Machiko Asaka1 and Koichi Node1

  1. 1Department of Cardiovascular Medicine, Saga University Faculty of Medicine, Saga, Japan
  2. 2Department of Bioscience and Genetics, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan

Correspondence: Dr T Hirase, Department of Bioscience and Genetics, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita 565-8565, Japan. E-mail: hirase@ri.ncvc.go.jp

Received 14 November 2010; Revised 6 March 2011; Accepted 21 March 2011; Published online 16 June 2011.

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Abstract

Angiotensin II has been implicated in vascular remodeling. Microtubule composed of tubulins regulates cell shape, migration and survival. Tubulin acetylation has an important role in the control of microtubule structure and microtubule-based cellular functions. In this study, angiotensin II induced disassembly and deacetylation of α-tubulin, which were blocked by pretreatment with an angiotensin II type 1 receptor blocker losartan and a sirtuin class deacetylase inhibitor sirtinol, and by depletion of a deacetylase SIRT2 using RNA interference. We investigated the involvement of SIRT2 in angiotensin II-induced endothelial cell migration using the Boyden chamber method. Angiotensin II caused a significant increase in cell migration, which was blocked by pretreatment with sirtinol and SIRT2 depletion. It has been reported that angiotensin II is involved in cytoskeletal reorganization stimulated by mechanical stretch in endothelial cells. We also demonstrated that endothelial cells subjected to a 10% uniaxial stretch showed vertical alignment to the direction of tension and tubulin deacetylation in the peripheral side of cells, in comparison with control static cells. The mechanical stretch-induced changes of microtubules were blocked by pretreatment with sirtinol and SIRT2 depletion. Immunofluorescence microscopy showed that acetylated tubulin was decreased in platelet-endothelial cell adhesion molecule-1-positive cells in the intima of the aortic walls in mice loaded with angiotensin II, in comparison with mice loaded with control vehicle. These data show that angiotensin II and mechanical stretch stimulate microtubule redistribution and deacetylation via SIRT2 in endothelial cells, suggesting the emerging role of SIRT2 in hypertension-induced vascular remodeling.

Keywords:

angiotensin II; cyclic stretch; endothelial cells; microtubule; SIRT2