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Ann Rehabil Med  <  Volume 21(2); 2017 <  Articles

Ann Geriatr Med Res 2017; 21(2): 78-85  https://doi.org/10.4235/agmr.2017.21.2.78
Effects of Homocysteine and Hyperglycemia on the Proliferation of Aortic Vascular Smooth Muscle Cells of Obese Type 2 Diabetes Rat
Hyung Joon Yoo1,*, Sung Hoon Yu1,2,*, Young Jung Cho3, Hong Woo Nam3, Dong Hyun Kang1
1Division of Endocrinology and Metabolism, Hallym University Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, 2Division of Endocrinology and Metabolism, Hanyang University College of Medicine, Seoul, 3Department of Internal Medicine, National Medical Center, Seoul, Korea
Correspondence to: Hyung Joon Yoo, MD, PhD
Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, 1 Singil-ro, Yeongdeungpo-gu, Seoul 07441, Korea
Tel: +82-2-2639-5691 Fax:+82-2-2677-9756 E-mail: hjoonyoo@gmail.com
*These authors contributed equally to this study and should be considered co-first authors.
Received: May 8, 2017; Revised: June 14, 2017; Accepted: June 14, 2017; Published online: June 30, 2017.
© The Korea Geriatrics Society. All rights reserved.

This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background: The aim of this study was to investigate the role of homocysteine on the proliferation of rat aortic vascular smooth muscle cells (VSMCs) by measuring mitogen-activated protein (MAP) kinase under hyperglycemic conditions. Methods: Rat aortic VSMCs were isolated from Otsuka Long-Evans Tokushima Fatty and Long-Evans Tokushima Otsuka rats. VSMCs were incubated in the presence of homocysteine (1 mM) with/without PD98059 (30 μM) and wortmannin (300 nM) for 48 hours in different concentrations of glucose (5.5, 25 mM). Proliferation was evaluated by methylthiazoletetrazolium (MTT), fluorescence-activated cell sorting (FACS), and western blot analyses. Results: In MTT and FACS analyses, the proliferation of VSMCs was increased by homocysteine. After PD98059 (30 μM) and wortmannin (300 nM) treatment with homocysteine (1 mM), the increased proliferation of VSMC caused by homocysteine, decreased to control levels. In Western blot analysis, immunoexpression of phospho-p44/42 MAP kinase was significantly increased by homocysteine (1 mM). After PD98059 and wortmannin treatment, the increased immunoexpression of phospho-p44/42 MAP kinase was suppressed. Conclusion: These results suggest that the MAP kinase and PI3 kinase pathways are the main mechanisms involved in rat VSMC proliferation caused by homocysteine under hyperglycemic conditions.
Keywords: Homocysteine, Hyperglycemia, Vascular smooth muscle cell, Mitogen-activated protein kinase, Phosphoinositide 3-kinase


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